Title

A Dose-escalating Clinical Trial With KH176
A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Clinical Trial With KH176
  • Phase

    Phase 1
  • Study Type

    Interventional
  • Intervention/Treatment

    kh176 ...
  • Study Participants

    32
Mitochondrial Diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), Leigh's Disease and Leber's Hereditary Optic Neuropathy (LHON). KH176 is a potent intracellular redox modulating agent targeting the reactive oxygen species which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. After demonstrating a favourable safety profile in the pre-clinical testing, the safety, tolerability and pharmacokinetic and pharmacodynamic characteristics of the compound will now be evaluated in healthy male subjects in this trial
Study Started
May 31
2015
Primary Completion
Sep 30
2015
Study Completion
Oct 31
2015
Results Posted
Nov 12
2020
Last Update
Oct 18
2021

Drug KH176

Drug placebo

Single Escalating Experimental

2 alternating groups receiving escalating single doses of active/placebo

Multiple Escalating Experimental

3 multiple escalating groups, receiving active/placebo

Criteria

Inclusion Criteria:

Healthy as assessed by medical history, physical examination, Vital Signs, Clinical Laboratory, ECG

Exclusion Criteria:

Allergies,
Concomitant medication,
concomitant disease,
relevant surgery,
recent blood donation

Summary

Group I Placebo

Group II Placebo

SAD Group I 10mg

SAD Group II 30mg

SAD Group I 100mg

SAD Group II 300mg

SAD Group I 800mg

SAD Group II 2000mg

Group I Placebo + Food

Group I 100mg + Food

MAD Group III 200mg

MAD Group IV 400mg

MAD Group V 800mg

Placebo

All Events

Event Type Organ System Event Term Group I Placebo Group II Placebo SAD Group I 10mg SAD Group II 30mg SAD Group I 100mg SAD Group II 300mg SAD Group I 800mg SAD Group II 2000mg Group I Placebo + Food Group I 100mg + Food MAD Group III 200mg MAD Group IV 400mg MAD Group V 800mg Placebo

SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.

Group I Placebo

Baseline (Pre-dose Day 1)

386.2
msec (Mean)
Standard Deviation: 17.2

Change from baseline (BL)at 1h

4.0
msec (Mean)
Standard Deviation: 2.8

Change from BL at 12h

1.8
msec (Mean)
Standard Deviation: 6.7

Change from BL at 24h

5.3
msec (Mean)
Standard Deviation: 12.4

Change from BL at 2h

0.5
msec (Mean)
Standard Deviation: 7.9

Change from BL at 4h

6.5
msec (Mean)
Standard Deviation: 9.4

Change from BL at 6h

6.2
msec (Mean)
Standard Deviation: 3.6

Change from BL at 8h

-0.8
msec (Mean)
Standard Deviation: 7.3

Change from BL at FU

-0.3
msec (Mean)
Standard Deviation: 12.4

Group II Placebo

Baseline (Pre-dose Day 1)

395.0
msec (Mean)
Standard Deviation: 9.8

Change from baseline (BL)at 1h

-2.0
msec (Mean)
Standard Deviation: 8.7

Change from BL at 12h

-5.2
msec (Mean)
Standard Deviation: 4.8

Change from BL at 24h

-7.5
msec (Mean)
Standard Deviation: 9.3

Change from BL at 2h

-4.0
msec (Mean)
Standard Deviation: 6.6

Change from BL at 4h

-2.2
msec (Mean)
Standard Deviation: 11.4

Change from BL at 6h

-2.7
msec (Mean)
Standard Deviation: 6.0

Change from BL at 8h

-7.2
msec (Mean)
Standard Deviation: 4.0

Change from BL at FU

2.8
msec (Mean)
Standard Deviation: 7.9

SAD Group I 10mg

Baseline (Pre-dose Day 1)

385.8
msec (Mean)
Standard Deviation: 14.8

Change from baseline (BL)at 1h

-0.3
msec (Mean)
Standard Deviation: 3.8

Change from BL at 12h

-1.8
msec (Mean)
Standard Deviation: 2.6

Change from BL at 24h

-4.0
msec (Mean)
Standard Deviation: 7.3

Change from BL at 2h

-1.8
msec (Mean)
Standard Deviation: 7.9

Change from BL at 4h

-3.8
msec (Mean)
Standard Deviation: 3.3

Change from BL at 6h

4.3
msec (Mean)
Standard Deviation: 6.3

Change from BL at 8h

-5.5
msec (Mean)
Standard Deviation: 7.4

Change from BL at FU

-1.3
msec (Mean)
Standard Deviation: 10.8

SAD Group II 30mg

Baseline (Pre-dose Day 1)

399.3
msec (Mean)
Standard Deviation: 8.3

Change from baseline (BL)at 1h

-3.5
msec (Mean)
Standard Deviation: 6.0

Change from BL at 12h

-7.3
msec (Mean)
Standard Deviation: 6.8

Change from BL at 24h

-4.8
msec (Mean)
Standard Deviation: 5.6

Change from BL at 2h

-4.8
msec (Mean)
Standard Deviation: 6.1

Change from BL at 4h

-4.3
msec (Mean)
Standard Deviation: 6.2

Change from BL at 6h

-4.0
msec (Mean)
Standard Deviation: 7.3

Change from BL at 8h

-1.8
msec (Mean)
Standard Deviation: 9.2

Change from BL at FU

2.8
msec (Mean)
Standard Deviation: 8.0

SAD Group I 100mg

Baseline (Pre-dose Day 1)

390.3
msec (Mean)
Standard Deviation: 14.6

Change from baseline (BL)at 1h

0.8
msec (Mean)
Standard Deviation: 4.0

Change from BL at 12h

Change from BL at 24h

0.3
msec (Mean)
Standard Deviation: 6.2

Change from BL at 2h

-4.8
msec (Mean)
Standard Deviation: 3.0

Change from BL at 4h

1.0
msec (Mean)
Standard Deviation: 5.7

Change from BL at 6h

-1.0
msec (Mean)
Standard Deviation: 8.3

Change from BL at 8h

4.3
msec (Mean)
Standard Deviation: 10.3

Change from BL at FU

2.8
msec (Mean)
Standard Deviation: 13.1

SAD Group II 300mg

Baseline (Pre-dose Day 1)

393.5
msec (Mean)
Standard Deviation: 14.2

Change from baseline (BL)at 1h

0.8
msec (Mean)
Standard Deviation: 5.7

Change from BL at 12h

Change from BL at 24h

-4.3
msec (Mean)
Standard Deviation: 6.5

Change from BL at 2h

1.5
msec (Mean)
Standard Deviation: 6.0

Change from BL at 4h

3.8
msec (Mean)
Standard Deviation: 12.3

Change from BL at 6h

5.8
msec (Mean)
Standard Deviation: 8.1

Change from BL at 8h

-1.8
msec (Mean)
Standard Deviation: 9.0

Change from BL at FU

5.0
msec (Mean)
Standard Deviation: 6.1

SAD Group I 800mg

Baseline (Pre-dose Day 1)

386.5
msec (Mean)
Standard Deviation: 10.9

Change from baseline (BL)at 1h

0.3
msec (Mean)
Standard Deviation: 7.6

Change from BL at 12h

8.0
msec (Mean)
Standard Deviation: 0.8

Change from BL at 24h

0.3
msec (Mean)
Standard Deviation: 9.7

Change from BL at 2h

7.8
msec (Mean)
Standard Deviation: 10.0

Change from BL at 4h

3.3
msec (Mean)
Standard Deviation: 7.2

Change from BL at 6h

5.5
msec (Mean)
Standard Deviation: 2.5

Change from BL at 8h

0.8
msec (Mean)
Standard Deviation: 7.5

Change from BL at FU

-5.0
msec (Mean)
Standard Deviation: 3.2

SAD Group II 2000mg

Baseline (Pre-dose Day 1)

385.3
msec (Mean)
Standard Deviation: 16.8

Change from baseline (BL)at 1h

28.8
msec (Mean)
Standard Deviation: 19.0

Change from BL at 12h

19.3
msec (Mean)
Standard Deviation: 11.1

Change from BL at 24h

11.3
msec (Mean)
Standard Deviation: 4.7

Change from BL at 2h

28.5
msec (Mean)
Standard Deviation: 14.1

Change from BL at 4h

26.0
msec (Mean)
Standard Deviation: 8.7

Change from BL at 6h

26.0
msec (Mean)
Standard Deviation: 7.9

Change from BL at 8h

23.3
msec (Mean)
Standard Deviation: 12.3

Change from BL at FU

3.3
msec (Mean)
Standard Deviation: 7.6

Group I Placebo + Food

Baseline (Pre-dose Day 1)

369.0
msec (Mean)
Standard Deviation: 14.1

Change from baseline (BL)at 1h

4.5
msec (Mean)
Standard Deviation: 19.1

Change from BL at 12h

5.5
msec (Mean)
Standard Deviation: 7.8

Change from BL at 24h

-1.0
msec (Mean)
Standard Deviation: 8.5

Change from BL at 2h

2.5
msec (Mean)
Standard Deviation: 13.4

Change from BL at 4h

8.5
msec (Mean)
Standard Deviation: 17.7

Change from BL at 6h

8.5
msec (Mean)
Standard Deviation: 12.0

Change from BL at 8h

-2.5
msec (Mean)
Standard Deviation: 13.4

Change from BL at FU

5.5
msec (Mean)
Standard Deviation: 10.6

Group I 100mg + Food

Baseline (Pre-dose Day 1)

386.5
msec (Mean)
Standard Deviation: 13.2

Change from baseline (BL)at 1h

5.8
msec (Mean)
Standard Deviation: 2.6

Change from BL at 12h

3.3
msec (Mean)
Standard Deviation: 6.2

Change from BL at 24h

-3.8
msec (Mean)
Standard Deviation: 4.0

Change from BL at 2h

1.8
msec (Mean)
Standard Deviation: 5.3

Change from BL at 4h

0.3
msec (Mean)
Standard Deviation: 3.9

Change from BL at 6h

6.0
msec (Mean)
Standard Deviation: 5.0

Change from BL at 8h

0.5
msec (Mean)
Standard Deviation: 5.4

Change from BL at FU

6.5
msec (Mean)
Standard Deviation: 13.0

Pharmacodynamics of KH176

Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group

MAD Group III

GSH/GSSG Day 7-0h

919.0
ratio GSH/GSSG (Mean)
Standard Deviation: 196

GSH/GSSG Day 7-12h

1361.0
ratio GSH/GSSG (Mean)
Standard Deviation: 606

GSH/GSSG Day 7-3h

779.0
ratio GSH/GSSG (Mean)
Standard Deviation: 87

GSH/GSSG Day 7-6h

1040.0
ratio GSH/GSSG (Mean)
Standard Deviation: 335

Ox glutathione (GSH)/Red Glutathati(GSSG) Day 1-0h

872.0
ratio GSH/GSSG (Mean)
Standard Deviation: 532

MAD Group IV

GSH/GSSG Day 7-0h

1923.0
ratio GSH/GSSG (Mean)
Standard Deviation: 433

GSH/GSSG Day 7-12h

1893.0
ratio GSH/GSSG (Mean)
Standard Deviation: 279

GSH/GSSG Day 7-3h

2045.0
ratio GSH/GSSG (Mean)
Standard Deviation: 338

GSH/GSSG Day 7-6h

2113.0
ratio GSH/GSSG (Mean)
Standard Deviation: 687

Ox glutathione (GSH)/Red Glutathati(GSSG) Day 1-0h

2083.0
ratio GSH/GSSG (Mean)
Standard Deviation: 674

MAD Group V

GSH/GSSG Day 7-0h

1918.0
ratio GSH/GSSG (Mean)
Standard Deviation: 1007

GSH/GSSG Day 7-12h

1875.0
ratio GSH/GSSG (Mean)
Standard Deviation: 697

GSH/GSSG Day 7-3h

1935.0
ratio GSH/GSSG (Mean)
Standard Deviation: 699

GSH/GSSG Day 7-6h

1993.0
ratio GSH/GSSG (Mean)
Standard Deviation: 863

Ox glutathione (GSH)/Red Glutathati(GSSG) Day 1-0h

2275.0
ratio GSH/GSSG (Mean)
Standard Deviation: 792

Placebo

GSH/GSSG Day 7-0h

1694.0
ratio GSH/GSSG (Mean)
Standard Deviation: 572

GSH/GSSG Day 7-12h

1680.0
ratio GSH/GSSG (Mean)
Standard Deviation: 657

GSH/GSSG Day 7-3h

1712.0
ratio GSH/GSSG (Mean)
Standard Deviation: 465

GSH/GSSG Day 7-6h

1718.0
ratio GSH/GSSG (Mean)
Standard Deviation: 542

Ox glutathione (GSH)/Red Glutathati(GSSG) Day 1-0h

1584.0
ratio GSH/GSSG (Mean)
Standard Deviation: 491

Relationship to Study Drug and Severity of Treatment-emergent Adverse Events

Placebo

Not related TEAE

3.0
TEAE

Possibly related

13.0
TEAE

Related

Serious TEAE

TEAE

17.0
TEAE

Unlikely related

1.0
TEAE

Group I Placebo

Not related TEAE

4.0
TEAE

Possibly related

1.0
TEAE

Related

Serious TEAE

TEAE

5.0
TEAE

Unlikely related

Group II Placebo

Not related TEAE

Possibly related

Related

Serious TEAE

TEAE

2.0
TEAE

Unlikely related

2.0
TEAE

SAD Group I 10mg

Not related TEAE

Possibly related

Related

Serious TEAE

TEAE

2.0
TEAE

Unlikely related

2.0
TEAE

SAD Group II 30mg

Not related TEAE

2.0
TEAE

Possibly related

Related

Serious TEAE

TEAE

5.0
TEAE

Unlikely related

3.0
TEAE

SAD Group I 100mg

Not related TEAE

6.0
TEAE

Possibly related

1.0
TEAE

Related

Serious TEAE

TEAE

7.0
TEAE

Unlikely related

SAD Group II 300mg

Not related TEAE

Possibly related

Related

1.0
TEAE

Serious TEAE

TEAE

1.0
TEAE

Unlikely related

SAD Group I 800mg

Not related TEAE

Possibly related

Related

Serious TEAE

TEAE

Unlikely related

SAD Group II 2000mg

Not related TEAE

Possibly related

3.0
TEAE

Related

25.0
TEAE

Serious TEAE

TEAE

28.0
TEAE

Unlikely related

Group I Placebo + Food

Not related TEAE

1.0
TEAE

Possibly related

Related

Serious TEAE

TEAE

1.0
TEAE

Unlikely related

Group I 100mg + Food

Not related TEAE

1.0
TEAE

Possibly related

Related

Serious TEAE

TEAE

1.0
TEAE

Unlikely related

MAD Group III 200mg

Not related TEAE

1.0
TEAE

Possibly related

7.0
TEAE

Related

Serious TEAE

TEAE

9.0
TEAE

Unlikely related

1.0
TEAE

MAD Group IV 400mg

Not related TEAE

1.0
TEAE

Possibly related

4.0
TEAE

Related

Serious TEAE

TEAE

6.0
TEAE

Unlikely related

1.0
TEAE

MAD Group V 800mg

Not related TEAE

3.0
TEAE

Possibly related

9.0
TEAE

Related

Serious TEAE

TEAE

14.0
TEAE

Unlikely related

2.0
TEAE

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

4.947
cells 10^6/µL (Mean)
Standard Deviation: 0.488

Change from BL at 24h

0.2
cells 10^6/µL (Mean)
Standard Deviation: 0.495

Change from BL at FU

0.003
cells 10^6/µL (Mean)
Standard Deviation: 0.215

Group II Placebo

Baseline (pre-dose Day 1)

4.933
cells 10^6/µL (Mean)
Standard Deviation: 0.307

Change from BL at 24h

0.095
cells 10^6/µL (Mean)
Standard Deviation: 0.260

Change from BL at FU

-0.013
cells 10^6/µL (Mean)
Standard Deviation: 0.149

SAD Group I 10mg

Baseline (pre-dose Day 1)

4.793
cells 10^6/µL (Mean)
Standard Deviation: 0.455

Change from BL at 24h

0.063
cells 10^6/µL (Mean)
Standard Deviation: 0.085

Change from BL at FU

0.185
cells 10^6/µL (Mean)
Standard Deviation: 0.104

SAD Group II 30mg

Baseline (pre-dose Day 1)

5.03
cells 10^6/µL (Mean)
Standard Deviation: 0.458

Change from BL at 24h

0.188
cells 10^6/µL (Mean)
Standard Deviation: 0.153

Change from BL at FU

-0.052
cells 10^6/µL (Mean)
Standard Deviation: 0.183

SAD Group I 100mg

Baseline (pre-dose Day 1)

4.953
cells 10^6/µL (Mean)
Standard Deviation: 0.247

Change from BL at 24h

0.17
cells 10^6/µL (Mean)
Standard Deviation: 0.250

Change from BL at FU

0.083
cells 10^6/µL (Mean)
Standard Deviation: 0.127

SAD Group II 300mg

Baseline (pre-dose Day 1)

5.137
cells 10^6/µL (Mean)
Standard Deviation: 0.393

Change from BL at 24h

0.065
cells 10^6/µL (Mean)
Standard Deviation: 0.197

Change from BL at FU

-0.147
cells 10^6/µL (Mean)
Standard Deviation: 0.041

SAD Group I 800mg

Baseline (pre-dose Day 1)

4.973
cells 10^6/µL (Mean)
Standard Deviation: 0.141

Change from BL at 24h

0.173
cells 10^6/µL (Mean)
Standard Deviation: 0.200

Change from BL at FU

-0.053
cells 10^6/µL (Mean)
Standard Deviation: 0.209

SAD Group II 2000mg

Baseline (pre-dose Day 1)

4.623
cells 10^6/µL (Mean)
Standard Deviation: 0.395

Change from BL at 24h

0.325
cells 10^6/µL (Mean)
Standard Deviation: 0.185

Change from BL at FU

0.125
cells 10^6/µL (Mean)
Standard Deviation: 0.182

Group I Placebo + Food

Baseline (pre-dose Day 1)

5.095
cells 10^6/µL (Mean)
Standard Deviation: 0.120

Change from BL at 24h

0.185
cells 10^6/µL (Mean)
Standard Deviation: 0.064

Change from BL at FU

-0.15
cells 10^6/µL (Mean)
Standard Deviation: 0.339

Group I 100mg + Food

Baseline (pre-dose Day 1)

4.985
cells 10^6/µL (Mean)
Standard Deviation: 0.343

Change from BL at 24h

0.115
cells 10^6/µL (Mean)
Standard Deviation: 0.208

Change from BL at FU

0.05
cells 10^6/µL (Mean)
Standard Deviation: 0.211

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)

Group I Placebo

Baseline

2.3
mm/hr (Mean)
Standard Deviation: 1.4

Change from BL at 24h

0.5
mm/hr (Mean)
Standard Deviation: 0.5

Change from BL at FU

0.3
mm/hr (Mean)
Standard Deviation: 1.2

Group II Placebo

Baseline

2.8
mm/hr (Mean)
Standard Deviation: 2.1

Change from BL at 24h

0.3
mm/hr (Mean)
Standard Deviation: 1.0

Change from BL at FU

0.3
mm/hr (Mean)
Standard Deviation: 1.5

SAD Group I 10mg

Baseline

1.3
mm/hr (Mean)
Standard Deviation: 0.5

Change from BL at 24h

Change from BL at FU

0.8
mm/hr (Mean)
Standard Deviation: 1.0

SAD Group II 30mg

Baseline

1.8
mm/hr (Mean)
Standard Deviation: 1.0

Change from BL at 24h

1.0
mm/hr (Mean)
Standard Deviation: 0.8

Change from BL at FU

0.5
mm/hr (Mean)
Standard Deviation: 1.7

SAD Group I 100mg

Baseline

2.0
mm/hr (Mean)
Standard Deviation: 1.4

Change from BL at 24h

Change from BL at FU

0.5
mm/hr (Mean)
Standard Deviation: 1.7

SAD Group II 300mg

Baseline

3.0
mm/hr (Mean)
Standard Deviation: 4.0

Change from BL at 24h

0.3
mm/hr (Mean)
Standard Deviation: 1.0

Change from BL at FU

SAD Group I 800mg

Baseline

7.3
mm/hr (Mean)
Standard Deviation: 8.5

Change from BL at 24h

0.3
mm/hr (Mean)
Standard Deviation: 0.6

Change from BL at FU

-2.3
mm/hr (Mean)
Standard Deviation: 6.8

SAD Group II 2000mg

Baseline

4.0
mm/hr (Mean)
Standard Deviation: 3.2

Change from BL at 24h

3.0
mm/hr (Mean)
Standard Deviation: 3.6

Change from BL at FU

0.5
mm/hr (Mean)
Standard Deviation: 1.0

Group I Placebo + Food

Baseline

5.0
mm/hr (Mean)
Standard Deviation: 2.8

Change from BL at 24h

-0.5
mm/hr (Mean)
Standard Deviation: 0.7

Change from BL at FU

Group I 100mg + Food

Baseline

2.5
mm/hr (Mean)
Standard Deviation: 3.0

Change from BL at 24h

1.0
mm/hr (Mean)
Standard Deviation: 2.0

Change from BL at FU

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group

MAD Group III

Baseline (pre-dose Day 1)

4.0
mm/hr (Mean)
Standard Deviation: 2.4

Change from BL at Day 3

2.0
mm/hr (Mean)
Standard Deviation: 3.5

Change from BL at Day 8

4.8
mm/hr (Mean)
Standard Deviation: 5.7

Change from BL at FU

5.0
mm/hr (Mean)
Standard Deviation: 8.2

MAD Group IV

Baseline (pre-dose Day 1)

3.0
mm/hr (Mean)
Standard Deviation: 1.8

Change from BL at Day 3

0.8
mm/hr (Mean)
Standard Deviation: 0.5

Change from BL at Day 8

0.8
mm/hr (Mean)
Standard Deviation: 2.2

Change from BL at FU

1.3
mm/hr (Mean)
Standard Deviation: 1.3

MAD Group V

Baseline (pre-dose Day 1)

2.0
mm/hr (Mean)
Standard Deviation: 1.4

Change from BL at Day 3

0.5
mm/hr (Mean)
Standard Deviation: 0.6

Change from BL at Day 8

2.5
mm/hr (Mean)
Standard Deviation: 1.7

Change from BL at FU

1.0
mm/hr (Mean)
Standard Deviation: 0.8

Placebo

Baseline (pre-dose Day 1)

2.7
mm/hr (Mean)
Standard Deviation: 1.8

Change from BL at Day 3

0.8
mm/hr (Mean)
Standard Deviation: 1.7

Change from BL at Day 8

0.3
mm/hr (Mean)
Standard Deviation: 1.4

Change from BL at FU

2.2
mm/hr (Mean)
Standard Deviation: 3.5

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group

Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

43.77
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 3.35

Change from BL at 24h

0.53
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.28

Change from BL at FU

-0.43
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.70

Group II Placebo

Baseline (pre-dose Day 1)

43.13
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.79

Change from BL at 24h

0.6
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.10

Change from BL at FU

-0.65
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.37

SAD Group I 10mg

Baseline (pre-dose Day 1)

43.1
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 3.46

Change from BL at 24h

0.75
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 0.91

Change from BL at FU

0.85
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.45

SAD Group II 30mg

Baseline (pre-dose Day 1)

44.38
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 3.28

Change from BL at 24h

1.95
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.41

Change from BL at FU

-0.93
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.91

SAD Group I 100mg

Baseline (pre-dose Day 1)

42.98
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.41

Change from BL at 24h

1.42
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.12

Change from BL at FU

0.1
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.66

SAD Group II 300mg

Baseline (pre-dose Day 1)

44.35
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.88

Change from BL at 24h

1.03
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.11

Change from BL at FU

-2.02
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 0.54

SAD Group I 800mg

Baseline (pre-dose Day 1)

44.05
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 3.17

Change from BL at 24h

1.33
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.80

Change from BL at FU

-1.15
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.17

SAD Group II 2000mg

Baseline (pre-dose Day 1)

41.35
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.68

Change from BL at 24h

2.33
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.87

Change from BL at FU

0.07
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.41

Group I Placebo + Food

Baseline (pre-dose Day 1)

44.35
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.33

Change from BL at 24h

1.9
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 0.28

Change from BL at FU

-0.65
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 3.04

Group I 100mg + Food

Baseline (pre-dose Day 1)

42.53
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.50

Change from BL at 24h

0.68
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 1.92

Change from BL at FU

0.55
%red cells to the volume of whole blood. (Mean)
Standard Deviation: 2.20

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

30.32
pg/cell (Mean)
Standard Deviation: 1.83

Change from BL at 24h - Day 1

0.08
pg/cell (Mean)
Standard Deviation: 0.34

Change from BL at FU

-0.22
pg/cell (Mean)
Standard Deviation: 0.15

Group II Placebo

Baseline (pre-dose Day 1)

29.7
pg/cell (Mean)
Standard Deviation: 0.98

Change from BL at 24h - Day 1

0.23
pg/cell (Mean)
Standard Deviation: 0.59

Change from BL at FU

0.05
pg/cell (Mean)
Standard Deviation: 0.46

SAD Group I 10mg

Baseline (pre-dose Day 1)

30.78
pg/cell (Mean)
Standard Deviation: 1.71

Change from BL at 24h - Day 1

0.17
pg/cell (Mean)
Standard Deviation: 0.26

Change from BL at FU

-0.28
pg/cell (Mean)
Standard Deviation: 0.57

SAD Group II 30mg

Baseline (pre-dose Day 1)

30.38
pg/cell (Mean)
Standard Deviation: 0.49

Change from BL at 24h - Day 1

-0.08
pg/cell (Mean)
Standard Deviation: 0.26

Change from BL at FU

-0.23
pg/cell (Mean)
Standard Deviation: 0.51

SAD Group I 100mg

Baseline (pre-dose Day 1)

30.0
pg/cell (Mean)
Standard Deviation: 1.75

Change from BL at 24h - Day 1

-0.15
pg/cell (Mean)
Standard Deviation: 0.13

Change from BL at FU

-0.42
pg/cell (Mean)
Standard Deviation: 0.37

SAD Group II 300mg

Baseline (pre-dose Day 1)

29.63
pg/cell (Mean)
Standard Deviation: 0.68

Change from BL at 24h - Day 1

-0.6
pg/cell (Mean)
Standard Deviation: 0.80

Change from BL at FU

-0.28
pg/cell (Mean)
Standard Deviation: 0.21

SAD Group I 800mg

Baseline (pre-dose Day 1)

30.28
pg/cell (Mean)
Standard Deviation: 1.26

Change from BL at 24h - Day 1

-0.25
pg/cell (Mean)
Standard Deviation: 0.37

Change from BL at FU

-0.58
pg/cell (Mean)
Standard Deviation: 0.22

SAD Group II 2000mg

Baseline (pre-dose Day 1)

29.8
pg/cell (Mean)
Standard Deviation: 1.16

Change from BL at 24h - Day 1

0.33
pg/cell (Mean)
Standard Deviation: 0.41

Change from BL at FU

0.12
pg/cell (Mean)
Standard Deviation: 0.39

Group I Placebo + Food

Baseline (pre-dose Day 1)

30.25
pg/cell (Mean)
Standard Deviation: 1.77

Change from BL at 24h - Day 1

0.25
pg/cell (Mean)
Standard Deviation: 0.64

Change from BL at FU

-0.15
pg/cell (Mean)
Standard Deviation: 0.35

Group I 100mg + Food

Baseline (pre-dose Day 1)

29.65
pg/cell (Mean)
Standard Deviation: 2.13

Change from BL at 24h - Day 1

0.2
pg/cell (Mean)
Standard Deviation: 0.34

Change from BL at FU

-0.08
pg/cell (Mean)
Standard Deviation: 0.15

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD

Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

34.15
g/dL RBC (Mean)
Standard Deviation: 0.34

Change from BL at 24h - Day 1

-0.07
g/dL RBC (Mean)
Standard Deviation: 0.32

Change from BL at FU

0.17
g/dL RBC (Mean)
Standard Deviation: 0.62

Group II Placebo

Baseline (pre-dose Day 1)

33.98
g/dL RBC (Mean)
Standard Deviation: 1.01

Change from BL at 24h - Day 1

0.43
g/dL RBC (Mean)
Standard Deviation: 0.42

Change from BL at FU

0.47
g/dL RBC (Mean)
Standard Deviation: 0.42

SAD Group I 10mg

Baseline (pre-dose Day 1)

34.18
g/dL RBC (Mean)
Standard Deviation: 0.46

Change from BL at 24h - Day 1

Change from BL at FU

0.27
g/dL RBC (Mean)
Standard Deviation: 0.54

SAD Group II 30mg

Baseline (pre-dose Day 1)

34.38
g/dL RBC (Mean)
Standard Deviation: 0.84

Change from BL at 24h - Day 1

-0.27
g/dL RBC (Mean)
Standard Deviation: 0.39

Change from BL at FU

0.18
g/dL RBC (Mean)
Standard Deviation: 0.60

SAD Group I 100mg

Baseline (pre-dose Day 1)

34.53
g/dL RBC (Mean)
Standard Deviation: 0.45

Change from BL at 24h - Day 1

-0.17
g/dL RBC (Mean)
Standard Deviation: 0.15

Change from BL at FU

-0.05
g/dL RBC (Mean)
Standard Deviation: 0.64

SAD Group II 300mg

Baseline (pre-dose Day 1)

34.33
g/dL RBC (Mean)
Standard Deviation: 1.07

Change from BL at 24h - Day 1

-1.05
g/dL RBC (Mean)
Standard Deviation: 0.87

Change from BL at FU

0.3
g/dL RBC (Mean)
Standard Deviation: 0.48

SAD Group I 800mg

Baseline (pre-dose Day 1)

34.2
g/dL RBC (Mean)
Standard Deviation: 0.65

Change from BL at 24h - Day 1

-0.2
g/dL RBC (Mean)
Standard Deviation: 0.42

Change from BL at FU

-0.13
g/dL RBC (Mean)
Standard Deviation: 0.61

SAD Group II 2000mg

Baseline (pre-dose Day 1)

33.25
g/dL RBC (Mean)
Standard Deviation: 0.71

Change from BL at 24h - Day 1

0.82
g/dL RBC (Mean)
Standard Deviation: 0.29

Change from BL at FU

1.0
g/dL RBC (Mean)
Standard Deviation: 0.12

Group I Placebo + Food

Baseline (pre-dose Day 1)

34.7
g/dL RBC (Mean)
Standard Deviation: 0.57

Change from BL at 24h - Day 1

0.1
g/dL RBC (Mean)
Standard Deviation: 0.57

Change from BL at FU

-0.6
g/dL RBC (Mean)
Standard Deviation: 0.28

Group I 100mg + Food

Baseline (pre-dose Day 1)

34.68
g/dL RBC (Mean)
Standard Deviation: 0.99

Change from BL at 24h - Day 1

0.45
g/dL RBC (Mean)
Standard Deviation: 0.68

Change from BL at FU

-0.2
g/dL RBC (Mean)
Standard Deviation: 0.42

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

88.75
fL (Mean)
Standard Deviation: 5.36

Change from BL at 24h

0.45
fL (Mean)
Standard Deviation: 0.85

Change from BL at FU

-1.1
fL (Mean)
Standard Deviation: 1.85

Group II Placebo

Baseline (pre-dose Day 1)

87.52
fL (Mean)
Standard Deviation: 3.71

Change from BL at 24h

-0.38
fL (Mean)
Standard Deviation: 1.09

Change from BL at FU

-1.03
fL (Mean)
Standard Deviation: 0.46

SAD Group I 10mg

Baseline (pre-dose Day 1)

90.15
fL (Mean)
Standard Deviation: 5.73

Change from BL at 24h

0.35
fL (Mean)
Standard Deviation: 0.37

Change from BL at FU

-1.68
fL (Mean)
Standard Deviation: 0.90

SAD Group II 30mg

Baseline (pre-dose Day 1)

88.35
fL (Mean)
Standard Deviation: 2.88

Change from BL at 24h

0.48
fL (Mean)
Standard Deviation: 0.41

Change from BL at FU

-0.92
fL (Mean)
Standard Deviation: 1.28

SAD Group I 100mg

Baseline (pre-dose Day 1)

86.93
fL (Mean)
Standard Deviation: 4.75

Change from BL at 24h

Change from BL at FU

-1.25
fL (Mean)
Standard Deviation: 1.54

SAD Group II 300mg

Baseline (pre-dose Day 1)

86.42
fL (Mean)
Standard Deviation: 2.83

Change from BL at 24h

0.85
fL (Mean)
Standard Deviation: 0.73

Change from BL at FU

-1.52
fL (Mean)
Standard Deviation: 0.69

SAD Group I 800mg

Baseline (pre-dose Day 1)

88.55
fL (Mean)
Standard Deviation: 4.57

Change from BL at 24h

-0.27
fL (Mean)
Standard Deviation: 0.21

Change from BL at FU

-1.45
fL (Mean)
Standard Deviation: 1.02

SAD Group II 2000mg

Baseline (pre-dose Day 1)

89.73
fL (Mean)
Standard Deviation: 4.24

Change from BL at 24h

-1.33
fL (Mean)
Standard Deviation: 0.72

Change from BL at FU

-2.3
fL (Mean)
Standard Deviation: 1.00

Group I Placebo + Food

Baseline (pre-dose Day 1)

87.1
fL (Mean)
Standard Deviation: 6.65

Change from BL at 24h

0.6
fL (Mean)
Standard Deviation: 0.28

Change from BL at FU

1.1
fL (Mean)
Standard Deviation: 0.28

Group I 100mg + Food

Baseline (pre-dose Day 1)

85.48
fL (Mean)
Standard Deviation: 4.36

Change from BL at 24h

-0.55
fL (Mean)
Standard Deviation: 0.79

Change from BL at FU

0.2
fL (Mean)
Standard Deviation: 0.81

MAD: Change From Baseline in ECG Results by Time Point: QTcF

The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.

MAD Group III

Baseline (Pre-dose Day 1)

397.3
msec (Mean)
Standard Deviation: 18.4

Change from BL at 24h - Day 1

-4.3
msec (Mean)
Standard Deviation: 6.6

Change from BL at 2h - Day 1

0.5
msec (Mean)
Standard Deviation: 7.5

Change from BL at FU

-2.3
msec (Mean)
Standard Deviation: 5.0

Change from BL at pre-dose Day 2

-4.3
msec (Mean)
Standard Deviation: 6.6

Change from BL at pre-dose Day 3

0.5
msec (Mean)
Standard Deviation: 8.6

Change from BL at pre-dose Day 4

2.5
msec (Mean)
Standard Deviation: 14.6

Change from BL at pre-dose Day 5

6.0
msec (Mean)
Standard Deviation: 13.3

Change from BL at pre-dose Day 6

-1.3
msec (Mean)
Standard Deviation: 12.5

Change from BL at pre-dose Day 7

-1.0
msec (Mean)
Standard Deviation: 11.9

Change from BL Day 7 at 12h - Day 7

-4.3
msec (Mean)
Standard Deviation: 4.6

Change from BL Day 7 at 1h - Day 7

-1.3
msec (Mean)
Standard Deviation: 10.2

Change from BL Day 7 at 2h - Day 7

-3.5
msec (Mean)
Standard Deviation: 2.5

Change from BL Day 7 at 4h

-7.5
msec (Mean)
Standard Deviation: 4.7

Change from BL Day 7 at 8h - Day 7

-11.3
msec (Mean)
Standard Deviation: 3.2

Change from BL Day 7 BL at 6h - Day 7

-1.8
msec (Mean)
Standard Deviation: 7.3

MAD Group IV

Baseline (Pre-dose Day 1)

384.3
msec (Mean)
Standard Deviation: 21.7

Change from BL at 24h - Day 1

0.5
msec (Mean)
Standard Deviation: 5.7

Change from BL at 2h - Day 1

5.5
msec (Mean)
Standard Deviation: 8.1

Change from BL at FU

4.0
msec (Mean)
Standard Deviation: 6.3

Change from BL at pre-dose Day 2

0.5
msec (Mean)
Standard Deviation: 5.7

Change from BL at pre-dose Day 3

2.8
msec (Mean)
Standard Deviation: 6.4

Change from BL at pre-dose Day 4

0.5
msec (Mean)
Standard Deviation: 13.6

Change from BL at pre-dose Day 5

2.5
msec (Mean)
Standard Deviation: 7.2

Change from BL at pre-dose Day 6

-1.5
msec (Mean)
Standard Deviation: 6.2

Change from BL at pre-dose Day 7

3.0
msec (Mean)
Standard Deviation: 9.5

Change from BL Day 7 at 12h - Day 7

-5.0
msec (Mean)
Standard Deviation: 3.5

Change from BL Day 7 at 1h - Day 7

-3.0
msec (Mean)
Standard Deviation: 3.3

Change from BL Day 7 at 2h - Day 7

-0.3
msec (Mean)
Standard Deviation: 8.2

Change from BL Day 7 at 4h

-3.8
msec (Mean)
Standard Deviation: 3.5

Change from BL Day 7 at 8h - Day 7

-3.8
msec (Mean)
Standard Deviation: 6.9

Change from BL Day 7 BL at 6h - Day 7

2.0
msec (Mean)
Standard Deviation: 4.7

MAD Group V

Baseline (Pre-dose Day 1)

388.5
msec (Mean)
Standard Deviation: 4.7

Change from BL at 24h - Day 1

3.3
msec (Mean)
Standard Deviation: 13.6

Change from BL at 2h - Day 1

7.3
msec (Mean)
Standard Deviation: 7.0

Change from BL at FU

-0.5
msec (Mean)
Standard Deviation: 14.4

Change from BL at pre-dose Day 2

3.3
msec (Mean)
Standard Deviation: 13.6

Change from BL at pre-dose Day 3

10.5
msec (Mean)
Standard Deviation: 17.2

Change from BL at pre-dose Day 4

7.3
msec (Mean)
Standard Deviation: 10.2

Change from BL at pre-dose Day 5

10.8
msec (Mean)
Standard Deviation: 6.7

Change from BL at pre-dose Day 6

7.8
msec (Mean)
Standard Deviation: 8.0

Change from BL at pre-dose Day 7

13.5
msec (Mean)
Standard Deviation: 8.7

Change from BL Day 7 at 12h - Day 7

-10.0
msec (Mean)
Standard Deviation: 4.7

Change from BL Day 7 at 1h - Day 7

-6.5
msec (Mean)
Standard Deviation: 8.1

Change from BL Day 7 at 2h - Day 7

-0.8
msec (Mean)
Standard Deviation: 3.2

Change from BL Day 7 at 4h

-5.8
msec (Mean)
Standard Deviation: 7.7

Change from BL Day 7 at 8h - Day 7

-11.0
msec (Mean)
Standard Deviation: 5.3

Change from BL Day 7 BL at 6h - Day 7

-7.3
msec (Mean)
Standard Deviation: 1.9

Placebo

Baseline (Pre-dose Day 1)

393.0
msec (Mean)
Standard Deviation: 18.8

Change from BL at 24h - Day 1

-4.8
msec (Mean)
Standard Deviation: 3.7

Change from BL at 2h - Day 1

1.7
msec (Mean)
Standard Deviation: 5.3

Change from BL at FU

6.7
msec (Mean)
Standard Deviation: 14.1

Change from BL at pre-dose Day 2

-4.8
msec (Mean)
Standard Deviation: 3.7

Change from BL at pre-dose Day 3

-7.5
msec (Mean)
Standard Deviation: 6.8

Change from BL at pre-dose Day 4

-6.7
msec (Mean)
Standard Deviation: 8.4

Change from BL at pre-dose Day 5

-5.3
msec (Mean)
Standard Deviation: 7.3

Change from BL at pre-dose Day 6

-8.2
msec (Mean)
Standard Deviation: 11.8

Change from BL at pre-dose Day 7

-8.8
msec (Mean)
Standard Deviation: 9.2

Change from BL Day 7 at 12h - Day 7

1.7
msec (Mean)
Standard Deviation: 6.0

Change from BL Day 7 at 1h - Day 7

-2.2
msec (Mean)
Standard Deviation: 2.7

Change from BL Day 7 at 2h - Day 7

-0.3
msec (Mean)
Standard Deviation: 10.1

Change from BL Day 7 at 4h

3.0
msec (Mean)
Standard Deviation: 11.2

Change from BL Day 7 at 8h - Day 7

0.8
msec (Mean)
Standard Deviation: 3.9

Change from BL Day 7 BL at 6h - Day 7

-0.5
msec (Mean)
Standard Deviation: 21.0

Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

4.435
cells 10^3/µL (Mean)
Standard Deviation: 0.526

Change from BL at 24h

0.343
cells 10^3/µL (Mean)
Standard Deviation: 0.525

Change from BL at FU

0.258
cells 10^3/µL (Mean)
Standard Deviation: 0.309

Group II Placebo

Baseline (pre-dose Day 1)

4.773
cells 10^3/µL (Mean)
Standard Deviation: 0.548

Change from BL at 24h

-0.057
cells 10^3/µL (Mean)
Standard Deviation: 0.359

Change from BL at FU

-0.203
cells 10^3/µL (Mean)
Standard Deviation: 0.662

SAD Group I 10mg

Baseline (pre-dose Day 1)

4.313
cells 10^3/µL (Mean)
Standard Deviation: 0.418

Change from BL at 24h

-0.033
cells 10^3/µL (Mean)
Standard Deviation: 0.317

Change from BL at FU

0.288
cells 10^3/µL (Mean)
Standard Deviation: 0.211

SAD Group II 30mg

Baseline (pre-dose Day 1)

4.863
cells 10^3/µL (Mean)
Standard Deviation: 0.372

Change from BL at 24h

0.16
cells 10^3/µL (Mean)
Standard Deviation: 0.329

Change from BL at FU

-0.073
cells 10^3/µL (Mean)
Standard Deviation: 0.367

SAD Group I 100mg

Baseline (pre-dose Day 1)

4.395
cells 10^3/µL (Mean)
Standard Deviation: 0.694

Change from BL at 24h

0.257
cells 10^3/µL (Mean)
Standard Deviation: 0.529

Change from BL at FU

0.395
cells 10^3/µL (Mean)
Standard Deviation: 0.617

SAD Group II 300mg

Baseline (pre-dose Day 1)

4.475
cells 10^3/µL (Mean)
Standard Deviation: 0.733

Change from BL at 24h

0.16
cells 10^3/µL (Mean)
Standard Deviation: 0.753

Change from BL at FU

-0.287
cells 10^3/µL (Mean)
Standard Deviation: 0.618

SAD Group I 800mg

Baseline (pre-dose Day 1)

4.853
cells 10^3/µL (Mean)
Standard Deviation: 0.372

Change from BL at 24h

0.528
cells 10^3/µL (Mean)
Standard Deviation: 0.324

Change from BL at FU

0.215
cells 10^3/µL (Mean)
Standard Deviation: 0.266

SAD Group II 2000mg

Baseline (pre-dose Day 1)

5.118
cells 10^3/µL (Mean)
Standard Deviation: 0.647

Change from BL at 24h

0.655
cells 10^3/µL (Mean)
Standard Deviation: 0.666

Change from BL at FU

-0.32
cells 10^3/µL (Mean)
Standard Deviation: 0.592

Group I Placebo + Food

Baseline (pre-dose Day 1)

5.815
cells 10^3/µL (Mean)
Standard Deviation: 2.072

Change from BL at 24h

0.22
cells 10^3/µL (Mean)
Standard Deviation: 0.721

Change from BL at FU

-0.56
cells 10^3/µL (Mean)
Standard Deviation: 1.202

Group I 100mg + Food

Baseline (pre-dose Day 1)

5.535
cells 10^3/µL (Mean)
Standard Deviation: 1.467

Change from BL at 24h

-0.28
cells 10^3/µL (Mean)
Standard Deviation: 0.555

Change from BL at FU

-0.745
cells 10^3/µL (Mean)
Standard Deviation: 1.535

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

1570.0
cells/µL (Mean)
Standard Deviation: 227.0

Change from BL at 24h

-13.3
cells/µL (Mean)
Standard Deviation: 223.4

Change from BL at FU

86.7
cells/µL (Mean)
Standard Deviation: 265.3

Group II Placebo

Baseline (pre-dose Day 1)

1748.3
cells/µL (Mean)
Standard Deviation: 441.1

Change from BL at 24h

-16.7
cells/µL (Mean)
Standard Deviation: 347.3

Change from BL at FU

-45.0
cells/µL (Mean)
Standard Deviation: 253.3

SAD Group I 10mg

Baseline (pre-dose Day 1)

1655.0
cells/µL (Mean)
Standard Deviation: 200.4

Change from BL at 24h

-45.0
cells/µL (Mean)
Standard Deviation: 192.8

Change from BL at FU

180.0
cells/µL (Mean)
Standard Deviation: 186.5

SAD Group II 30mg

Baseline (pre-dose Day 1)

1862.5
cells/µL (Mean)
Standard Deviation: 548.2

Change from BL at 24h

-172.5
cells/µL (Mean)
Standard Deviation: 227.1

Change from BL at FU

-92.5
cells/µL (Mean)
Standard Deviation: 315.7

SAD Group I 100mg

Baseline (pre-dose Day 1)

1485.0
cells/µL (Mean)
Standard Deviation: 169.2

Change from BL at 24h

-27.5
cells/µL (Mean)
Standard Deviation: 58.0

Change from BL at FU

127.5
cells/µL (Mean)
Standard Deviation: 425.2

SAD Group II 300mg

Baseline (pre-dose Day 1)

1570.0
cells/µL (Mean)
Standard Deviation: 273.1

Change from BL at 24h

92.5
cells/µL (Mean)
Standard Deviation: 225.6

Change from BL at FU

-32.5
cells/µL (Mean)
Standard Deviation: 174.6

SAD Group I 800mg

Baseline (pre-dose Day 1)

1550.0
cells/µL (Mean)
Standard Deviation: 275.3

Change from BL at 24h

287.5
cells/µL (Mean)
Standard Deviation: 353.7

Change from BL at FU

135.0
cells/µL (Mean)
Standard Deviation: 294.2

SAD Group II 2000mg

Baseline (pre-dose Day 1)

1497.5
cells/µL (Mean)
Standard Deviation: 707.6

Change from BL at 24h

37.5
cells/µL (Mean)
Standard Deviation: 159.9

Change from BL at FU

-7.5
cells/µL (Mean)
Standard Deviation: 244.0

Group I Placebo + Food

Baseline (pre-dose Day 1)

2260.0
cells/µL (Mean)
Standard Deviation: 975.8

Change from BL at 24h

-135.0
cells/µL (Mean)
Standard Deviation: 261.6

Change from BL at FU

-190.0
cells/µL (Mean)
Standard Deviation: 410.1

Group I 100mg + Food

Baseline (pre-dose Day 1)

1640.0
cells/µL (Mean)
Standard Deviation: 243.2

Change from BL at 24h

-70.0
cells/µL (Mean)
Standard Deviation: 177.6

Change from BL at FU

-27.5
cells/µL (Mean)
Standard Deviation: 125.8

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo + Food

Baseline (pre-dose Day 1)

2280.0
cells/µL (Mean)
Standard Deviation: 169.7

Change from BL at 24h

445.0
cells/µL (Mean)
Standard Deviation: 459.6

Change from BL at FU

-205.0
cells/µL (Mean)
Standard Deviation: 445.5

Group I 100mg + Food

Baseline (pre-dose Day 1)

3192.5
cells/µL (Mean)
Standard Deviation: 1523.9

Change from BL at 24h

-122.5
cells/µL (Mean)
Standard Deviation: 584.3

Change from BL at FU

-557.5
cells/µL (Mean)
Standard Deviation: 1326.2

Group I Placebo

Baseline (pre-dose Day 1)

2276.7
cells/µL (Mean)
Standard Deviation: 551.2

Change from BL at 24h

356.7
cells/µL (Mean)
Standard Deviation: 336.9

Change from BL at FU

205.0
cells/µL (Mean)
Standard Deviation: 161.8

Group II Placebo

Baseline (pre-dose Day 1)

2296.7
cells/µL (Mean)
Standard Deviation: 658.7

Change from BL at 24h

98.3
cells/µL (Mean)
Standard Deviation: 171.2

Change from BL at FU

-16.7
cells/µL (Mean)
Standard Deviation: 335.4

SAD Group I 10mg

Baseline (pre-dose Day 1)

2117.5
cells/µL (Mean)
Standard Deviation: 369.2

Change from BL at 24h

7.5
cells/µL (Mean)
Standard Deviation: 196.7

Change from BL at FU

90.0
cells/µL (Mean)
Standard Deviation: 183.5

SAD Group II 30mg

Baseline (pre-dose Day 1)

2365.0
cells/µL (Mean)
Standard Deviation: 820.8

Change from BL at 24h

410.0
cells/µL (Mean)
Standard Deviation: 593.0

Change from BL at FU

107.5
cells/µL (Mean)
Standard Deviation: 252.1

SAD Group I 100mg

Baseline (pre-dose Day 1)

2380.0
cells/µL (Mean)
Standard Deviation: 679.0

Change from BL at 24h

272.5
cells/µL (Mean)
Standard Deviation: 419.1

Change from BL at FU

255.0
cells/µL (Mean)
Standard Deviation: 519.0

SAD Group II 300mg

Baseline (pre-dose Day 1)

2197.5
cells/µL (Mean)
Standard Deviation: 835.9

Change from BL at 24h

165.0
cells/µL (Mean)
Standard Deviation: 335.5

Change from BL at FU

-167.5
cells/µL (Mean)
Standard Deviation: 480.7

SAD Group I 800mg

Baseline (pre-dose Day 1)

2565.0
cells/µL (Mean)
Standard Deviation: 462.6

Change from BL at 24h

285.0
cells/µL (Mean)
Standard Deviation: 155.0

Change from BL at FU

-12.5
cells/µL (Mean)
Standard Deviation: 203.5

SAD Group II 2000mg

Baseline (pre-dose Day 1)

2360.0
cells/µL (Mean)
Standard Deviation: 438.1

Change from BL at 24h

440.0
cells/µL (Mean)
Standard Deviation: 601.5

Change from BL at FU

-382.5
cells/µL (Mean)
Standard Deviation: 232.9

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group

Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value

MAD Group III

Baseline

39.93
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.20

Change from BL at Day 3

2.67
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.94

Change from BL at Day 8

3.3
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.24

Change from BL at FU

0.92
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.06

MAD Group IV

Baseline

43.4
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 3.51

Change from BL at Day 3

1.17
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.69

Change from BL at Day 8

1.22
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 3.26

Change from BL at FU

-0.1
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 3.26

MAD Group V

Baseline

45.1
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.33

Change from BL at Day 3

0.13
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 0.45

Change from BL at Day 8

0.1
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.22

Change from BL at FU

-1.05
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 0.64

Placebo

Baseline

43.3
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.95

Change from BL at Day 3

1.7
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 1.91

Change from BL at Day 8

1.93
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 2.69

Change from BL at FU

-0.75
% of red cells to volume of whole blood. (Mean)
Standard Deviation: 2.32

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

115.0
cells/µL (Mean)
Standard Deviation: 50.1

Change from BL at 24h

-5.0
cells/µL (Mean)
Standard Deviation: 16.4

Change from BL at FU

-13.3
cells/µL (Mean)
Standard Deviation: 16.3

Group II Placebo

Baseline (pre-dose Day 1)

191.7
cells/µL (Mean)
Standard Deviation: 109.4

Change from BL at 24h

-50.0
cells/µL (Mean)
Standard Deviation: 40.5

Change from BL at FU

-58.3
cells/µL (Mean)
Standard Deviation: 93.5

SAD Group I 10mg

Baseline (pre-dose Day 1)

110.0
cells/µL (Mean)
Standard Deviation: 49.7

Change from BL at 24h

-17.5
cells/µL (Mean)
Standard Deviation: 9.6

Change from BL at FU

-17.5
cells/µL (Mean)
Standard Deviation: 25.0

SAD Group II 30mg

Baseline (pre-dose Day 1)

137.5
cells/µL (Mean)
Standard Deviation: 83.4

Change from BL at 24h

-22.5
cells/µL (Mean)
Standard Deviation: 42.7

Change from BL at FU

-12.5
cells/µL (Mean)
Standard Deviation: 43.5

SAD Group I 100mg

Baseline (pre-dose Day 1)

112.5
cells/µL (Mean)
Standard Deviation: 36.9

Change from BL at 24h

-15.0
cells/µL (Mean)
Standard Deviation: 12.9

Change from BL at FU

-2.5
cells/µL (Mean)
Standard Deviation: 18.9

SAD Group II 300mg

Baseline (pre-dose Day 1)

200.0
cells/µL (Mean)
Standard Deviation: 78.7

Change from BL at 24h

-37.5
cells/µL (Mean)
Standard Deviation: 47.9

Change from BL at FU

-42.5
cells/µL (Mean)
Standard Deviation: 61.3

SAD Group I 800mg

Baseline (pre-dose Day 1)

245.0
cells/µL (Mean)
Standard Deviation: 233.6

Change from BL at 24h

-25.0
cells/µL (Mean)
Standard Deviation: 33.2

Change from BL at FU

77.5
cells/µL (Mean)
Standard Deviation: 201.6

SAD Group II 2000mg

Baseline (pre-dose Day 1)

110.0
cells/µL (Mean)
Standard Deviation: 71.6

Change from BL at 24h

-25.0
cells/µL (Mean)
Standard Deviation: 26.5

Change from BL at FU

-20.0
cells/µL (Mean)
Standard Deviation: 18.3

Group I Placebo + Food

Baseline (pre-dose Day 1)

650.0
cells/µL (Mean)
Standard Deviation: 792.0

Change from BL at 24h

-25.0
cells/µL (Mean)
Standard Deviation: 7.1

Change from BL at FU

-125.0
cells/µL (Mean)
Standard Deviation: 205.1

Group I 100mg + Food

Baseline (pre-dose Day 1)

152.5
cells/µL (Mean)
Standard Deviation: 81.0

Change from BL at 24h

-30.0
cells/µL (Mean)
Standard Deviation: 47.6

Change from BL at FU

-42.5
cells/µL (Mean)
Standard Deviation: 42.7

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

209.5
cells 10^3/µL (Mean)
Standard Deviation: 45.9

Change from BL at 24h

Change from BL at FU

11.8
cells 10^3/µL (Mean)
Standard Deviation: 14.0

Group II Placebo

Baseline (pre-dose Day 1)

204.0
cells 10^3/µL (Mean)
Standard Deviation: 15.7

Change from BL at 24h

4.8
cells 10^3/µL (Mean)
Standard Deviation: 6.1

Change from BL at FU

22.5
cells 10^3/µL (Mean)
Standard Deviation: 15.7

SAD Group I 10mg

Baseline (pre-dose Day 1)

193.0
cells 10^3/µL (Mean)
Standard Deviation: 31.9

Change from BL at 24h

8.5
cells 10^3/µL (Mean)
Standard Deviation: 12.4

Change from BL at FU

23.8
cells 10^3/µL (Mean)
Standard Deviation: 7.4

SAD Group II 30mg

Baseline (pre-dose Day 1)

223.0
cells 10^3/µL (Mean)
Standard Deviation: 21.6

Change from BL at 24h

2.3
cells 10^3/µL (Mean)
Standard Deviation: 12.8

Change from BL at FU

8.5
cells 10^3/µL (Mean)
Standard Deviation: 24.3

SAD Group I 100mg

Baseline (pre-dose Day 1)

215.8
cells 10^3/µL (Mean)
Standard Deviation: 64.0

Change from BL at 24h

3.8
cells 10^3/µL (Mean)
Standard Deviation: 20.3

Change from BL at FU

16.3
cells 10^3/µL (Mean)
Standard Deviation: 14.5

SAD Group II 300mg

Baseline (pre-dose Day 1)

203.8
cells 10^3/µL (Mean)
Standard Deviation: 7.0

Change from BL at 24h

-14.5
cells 10^3/µL (Mean)
Standard Deviation: 29.7

Change from BL at FU

7.3
cells 10^3/µL (Mean)
Standard Deviation: 7.9

SAD Group I 800mg

Baseline (pre-dose Day 1)

202.3
cells 10^3/µL (Mean)
Standard Deviation: 54.5

Change from BL at 24h

22.3
cells 10^3/µL (Mean)
Standard Deviation: 13.5

Change from BL at FU

15.8
cells 10^3/µL (Mean)
Standard Deviation: 14.3

SAD Group II 2000mg

Baseline (pre-dose Day 1)

160.1
cells 10^3/µL (Mean)
Standard Deviation: 100.8

Change from BL at 24h

23.0
cells 10^3/µL (Mean)
Standard Deviation: 22.8

Change from BL at FU

21.5
cells 10^3/µL (Mean)
Standard Deviation: 22.4

Group I Placebo + Food

Baseline (pre-dose Day 1)

204.5
cells 10^3/µL (Mean)
Standard Deviation: 67.2

Change from BL at 24h

4.0
cells 10^3/µL (Mean)
Standard Deviation: 7.1

Change from BL at FU

1.0
cells 10^3/µL (Mean)
Standard Deviation: 15.6

Group I 100mg + Food

Baseline (pre-dose Day 1)

215.8
cells 10^3/µL (Mean)
Standard Deviation: 55.6

Change from BL at 24h

0.3
cells 10^3/µL (Mean)
Standard Deviation: 9.0

Change from BL at FU

16.3
cells 10^3/µL (Mean)
Standard Deviation: 12.5

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

23.3
cells/µL (Mean)
Standard Deviation: 5.2

Change from BL at 24h

-5.0
cells/µL (Mean)
Standard Deviation: 8.4

Change from BL at FU

Group II Placebo

Baseline (pre-dose Day 1)

25.0
cells/µL (Mean)
Standard Deviation: 10.5

Change from BL at 24h

Change from BL at FU

-1.7
cells/µL (Mean)
Standard Deviation: 7.5

SAD Group I 10mg

Baseline (pre-dose Day 1)

15.0
cells/µL (Mean)
Standard Deviation: 5.8

Change from BL at 24h

2.5
cells/µL (Mean)
Standard Deviation: 5.0

Change from BL at FU

5.0
cells/µL (Mean)
Standard Deviation: 5.8

SAD Group II 30mg

Baseline (pre-dose Day 1)

30.0
cells/µL (Mean)
Standard Deviation: 18.3

Change from BL at 24h

-7.5
cells/µL (Mean)
Standard Deviation: 9.6

Change from BL at FU

-5.0
cells/µL (Mean)
Standard Deviation: 10.0

SAD Group I 100mg

Baseline (pre-dose Day 1)

15.0
cells/µL (Mean)
Standard Deviation: 10.0

Change from BL at 24h

Change from BL at FU

7.5
cells/µL (Mean)
Standard Deviation: 9.6

SAD Group II 300mg

Baseline (pre-dose Day 1)

32.5
cells/µL (Mean)
Standard Deviation: 15.0

Change from BL at 24h

-5.0
cells/µL (Mean)
Standard Deviation: 10.0

Change from BL at FU

-5.0
cells/µL (Mean)
Standard Deviation: 12.9

SAD Group I 800mg

Baseline (pre-dose Day 1)

20.0
cells/µL (Mean)
Standard Deviation: 11.5

Change from BL at 24h

2.5
cells/µL (Mean)
Standard Deviation: 5.0

Change from BL at FU

20.0
cells/µL (Mean)
Standard Deviation: 21.6

SAD Group II 2000mg

Baseline (pre-dose Day 1)

22.5
cells/µL (Mean)
Standard Deviation: 5.0

Change from BL at 24h

5.0
cells/µL (Mean)
Standard Deviation: 5.8

Change from BL at FU

Group I Placebo + Food

Baseline (pre-dose Day 1)

65.0
cells/µL (Mean)
Standard Deviation: 63.6

Change from BL at 24h

-20.0
cells/µL (Mean)
Standard Deviation: 14.1

Change from BL at FU

-15.0
cells/µL (Mean)
Standard Deviation: 21.2

Group I 100mg + Food

Baseline (pre-dose Day 1)

25.0
cells/µL (Mean)
Standard Deviation: 17.3

Change from BL at 24h

-2.5
cells/µL (Mean)
Standard Deviation: 9.6

Change from BL at FU

-2.5
cells/µL (Mean)
Standard Deviation: 5.0

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

Group I Placebo

Baseline (pre-dose Day 1)

445.0
cells/µL (Mean)
Standard Deviation: 78.2

Change from BL at 24h

1.7
cells/µL (Mean)
Standard Deviation: 46.7

Change from BL at FU

-21.7
cells/µL (Mean)
Standard Deviation: 91.5

Group II Placebo

Baseline (pre-dose Day 1)

496.7
cells/µL (Mean)
Standard Deviation: 71.7

Change from BL at 24h

-81.7
cells/µL (Mean)
Standard Deviation: 54.9

Change from BL at FU

-78.3
cells/µL (Mean)
Standard Deviation: 74.9

SAD Group I 10mg

Baseline (pre-dose Day 1)

407.5
cells/µL (Mean)
Standard Deviation: 79.3

Change from BL at 24h

20.0
cells/µL (Mean)
Standard Deviation: 78.3

Change from BL at FU

30.0
cells/µL (Mean)
Standard Deviation: 136.4

SAD Group II 30mg

Baseline (pre-dose Day 1)

455.0
cells/µL (Mean)
Standard Deviation: 81.9

Change from BL at 24h

-45.0
cells/µL (Mean)
Standard Deviation: 19.3

Change from BL at FU

-70.0
cells/µL (Mean)
Standard Deviation: 94.9

SAD Group I 100mg

Baseline (pre-dose Day 1)

397.5
cells/µL (Mean)
Standard Deviation: 133.0

Change from BL at 24h

20.0
cells/µL (Mean)
Standard Deviation: 122.7

Change from BL at FU

5.0
cells/µL (Mean)
Standard Deviation: 128.2

SAD Group II 300mg

Baseline (pre-dose Day 1)

467.5
cells/µL (Mean)
Standard Deviation: 98.8

Change from BL at 24h

-62.5
cells/µL (Mean)
Standard Deviation: 185.5

Change from BL at FU

-42.5
cells/µL (Mean)
Standard Deviation: 86.6

SAD Group I 800mg

Baseline (pre-dose Day 1)

462.5
cells/µL (Mean)
Standard Deviation: 147.1

Change from BL at 24h

-25.0
cells/µL (Mean)
Standard Deviation: 112.4

Change from BL at FU

SAD Group II 2000mg

Baseline (pre-dose Day 1)

470.0
cells/µL (Mean)
Standard Deviation: 87.6

Change from BL at 24h

2.5
cells/µL (Mean)
Standard Deviation: 56.8

Change from BL at FU

-47.5
cells/µL (Mean)
Standard Deviation: 63.4

Group I Placebo + Food

Baseline (pre-dose Day 1)

550.0
cells/µL (Mean)
Standard Deviation: 70.7

Change from BL at 24h

-45.0
cells/µL (Mean)
Standard Deviation: 21.2

Change from BL at FU

-20.0
cells/µL (Mean)
Standard Deviation: 127.3

Group I 100mg + Food

Baseline (pre-dose Day 1)

512.5
cells/µL (Mean)
Standard Deviation: 133.5

Change from BL at 24h

-55.0
cells/µL (Mean)
Standard Deviation: 70.5

Change from BL at FU

-110.0
cells/µL (Mean)
Standard Deviation: 128.3

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD Group III

Baseline (pre-dose Day 1)

87.0
fL (Mean)
Standard Deviation: 0.62

Change from BL at Day 3

-0.05
fL (Mean)
Standard Deviation: 0.40

Change from BL at Day 8

-0.1
fL (Mean)
Standard Deviation: 1.30

Change from BL at FU

0.6
fL (Mean)
Standard Deviation: 0.74

MAD Group IV

Baseline (pre-dose Day 1)

89.32
fL (Mean)
Standard Deviation: 2.73

Change from BL at Day 3

0.52
fL (Mean)
Standard Deviation: 1.15

Change from BL at Day 8

-0.43
fL (Mean)
Standard Deviation: 0.28

Change from BL at FU

-0.55
fL (Mean)
Standard Deviation: 0.73

MAD Group V

Baseline (pre-dose Day 1)

86.43
fL (Mean)
Standard Deviation: 1.29

Change from BL at Day 3

0.55
fL (Mean)
Standard Deviation: 0.71

Change from BL at Day 8

0.32
fL (Mean)
Standard Deviation: 0.90

Change from BL at FU

1.22
fL (Mean)
Standard Deviation: 1.31

Placebo

Baseline (pre-dose Day 1)

89.02
fL (Mean)
Standard Deviation: 2.93

Change from BL at Day 3

0.4
fL (Mean)
Standard Deviation: 1.08

Change from BL at Day 8

0.28
fL (Mean)
Standard Deviation: 0.95

Change from BL at FU

0.65
fL (Mean)
Standard Deviation: 0.77

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD Group III

Baseline (pre-dose Day 1)

13.68
g/dL (Mean)
Standard Deviation: 0.59

Change from BL at Day 3

1.05
g/dL (Mean)
Standard Deviation: 0.66

Change from BL at Day 8

1.35
g/dL (Mean)
Standard Deviation: 0.37

Change from BL at FU

0.3
g/dL (Mean)
Standard Deviation: 0.49

MAD Group IV

Baseline (pre-dose Day 1)

15.23
g/dL (Mean)
Standard Deviation: 1.38

Change from BL at Day 3

0.42
g/dL (Mean)
Standard Deviation: 0.74

Change from BL at Day 8

0.55
g/dL (Mean)
Standard Deviation: 1.22

Change from BL at FU

-0.05
g/dL (Mean)
Standard Deviation: 1.11

MAD Group V

Baseline (pre-dose Day 1)

15.68
g/dL (Mean)
Standard Deviation: 0.64

Change from BL at Day 3

0.17
g/dL (Mean)
Standard Deviation: 0.22

Change from BL at Day 8

0.27
g/dL (Mean)
Standard Deviation: 0.60

Change from BL at FU

-0.38
g/dL (Mean)
Standard Deviation: 0.47

Placebo

Baseline (pre-dose Day 1)

14.82
g/dL (Mean)
Standard Deviation: 0.67

Change from BL at Day 3

0.62
g/dL (Mean)
Standard Deviation: 0.50

Change from BL at Day 8

0.75
g/dL (Mean)
Standard Deviation: 0.83

Change from BL at FU

-0.35
g/dL (Mean)
Standard Deviation: 0.63

Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD

Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD Group III

Baseline (pre-dose Day 1)

5.463
cells 10^3/µL (Mean)
Standard Deviation: 0.579

Change from BL at Day 3

-0.435
cells 10^3/µL (Mean)
Standard Deviation: 0.631

Change from BL at Day 8

0.223
cells 10^3/µL (Mean)
Standard Deviation: 2.237

Change from BL at FU

0.06
cells 10^3/µL (Mean)
Standard Deviation: 2.519

MAD Group IV

Baseline (pre-dose Day 1)

4.753
cells 10^3/µL (Mean)
Standard Deviation: 0.410

Change from BL at Day 3

0.48
cells 10^3/µL (Mean)
Standard Deviation: 0.787

Change from BL at Day 8

0.48
cells 10^3/µL (Mean)
Standard Deviation: 0.252

Change from BL at FU

0.23
cells 10^3/µL (Mean)
Standard Deviation: 0.870

MAD Group V

Baseline (pre-dose Day 1)

5.378
cells 10^3/µL (Mean)
Standard Deviation: 1.221

Change from BL at Day 3

0.895
cells 10^3/µL (Mean)
Standard Deviation: 0.940

Change from BL at Day 8

0.795
cells 10^3/µL (Mean)
Standard Deviation: 0.178

Change from BL at FU

1.34
cells 10^3/µL (Mean)
Standard Deviation: 0.546

Placebo

Baseline (pre-dose Day 1)

4.583
cells 10^3/µL (Mean)
Standard Deviation: 0.487

Change from BL at Day 3

0.277
cells 10^3/µL (Mean)
Standard Deviation: 0.932

Change from BL at Day 8

0.563
cells 10^3/µL (Mean)
Standard Deviation: 0.983

Change from BL at FU

-0.14
cells 10^3/µL (Mean)
Standard Deviation: 0.930

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD Group III

Baseline (pre-dose Day 1)

3077.5
cells/µL (Mean)
Standard Deviation: 569.5

Change from BL at Day 3

-567.5
cells/µL (Mean)
Standard Deviation: 667.9

Change from BL at Day 8

105.0
cells/µL (Mean)
Standard Deviation: 2079.7

Change from BL at FU

185.0
cells/µL (Mean)
Standard Deviation: 2317.4

MAD Group IV

Baseline (pre-dose Day 1)

2602.5
cells/µL (Mean)
Standard Deviation: 582.4

Change from BL at Day 3

350.0
cells/µL (Mean)
Standard Deviation: 602.4

Change from BL at Day 8

312.5
cells/µL (Mean)
Standard Deviation: 355.1

Change from BL at FU

177.5
cells/µL (Mean)
Standard Deviation: 827.7

MAD Group V

Baseline (pre-dose Day 1)

2935.0
cells/µL (Mean)
Standard Deviation: 966.6

Change from BL at Day 3

437.5
cells/µL (Mean)
Standard Deviation: 505.3

Change from BL at Day 8

537.5
cells/µL (Mean)
Standard Deviation: 174.6

Change from BL at FU

1010.0
cells/µL (Mean)
Standard Deviation: 622.7

Placebo

Baseline (pre-dose Day 1)

2483.3
cells/µL (Mean)
Standard Deviation: 583.6

Change from BL at Day 3

81.7
cells/µL (Mean)
Standard Deviation: 540.7

Change from BL at Day 8

261.0
cells/µL (Mean)
Standard Deviation: 634.9

Change from BL at FU

-75.0
cells/µL (Mean)
Standard Deviation: 532.1

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD Group III

Baseline (pre-dose Day 1)

34.28
g/dL RBC (Mean)
Standard Deviation: 1.08

Change from BL at Day 3

0.3
g/dL RBC (Mean)
Standard Deviation: 0.22

Change from BL at Day 8

0.47
g/dL RBC (Mean)
Standard Deviation: 0.43

Change from BL at FU

-0.08
g/dL RBC (Mean)
Standard Deviation: 0.33

MAD Group IV

Baseline (pre-dose Day 1)

35.05
g/dL RBC (Mean)
Standard Deviation: 0.37

Change from BL at Day 3

0.05
g/dL RBC (Mean)
Standard Deviation: 0.62

Change from BL at Day 8

0.25
g/dL RBC (Mean)
Standard Deviation: 0.26

Change from BL at FU

MAD Group V

Baseline (pre-dose Day 1)

34.75
g/dL RBC (Mean)
Standard Deviation: 0.62

Change from BL at Day 3

0.3
g/dL RBC (Mean)
Standard Deviation: 0.39

Change from BL at Day 8

0.5
g/dL RBC (Mean)
Standard Deviation: 0.44

Change from BL at FU

Placebo

Baseline (pre-dose Day 1)

34.23
g/dL RBC (Mean)
Standard Deviation: 0.37

Change from BL at Day 3

0.08
g/dL RBC (Mean)
Standard Deviation: 0.48

Change from BL at Day 8

0.17
g/dL RBC (Mean)
Standard Deviation: 0.38

Change from BL at FU

-0.22
g/dL RBC (Mean)
Standard Deviation: 0.44

Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group

Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.

MAD Group III

Baseline (pre-dose Day 1)

1627.5
cells/µL (Mean)
Standard Deviation: 656.0

Change from BL at Day 3

87.5
cells/µL (Mean)
Standard Deviation: 177.8

Change from BL at Day 8

12.5
cells/µL (Mean)
Standard Deviation: 378.5

Change from BL at FU

-55.0
cells/µL (Mean)
Standard Deviation: 257.5

MAD Group IV

Baseline (pre-dose Day 1)

1498.5
cells/µL (Mean)
Standard Deviation: 125.1

Change from BL at Day 3

159.0
cells/µL (Mean)
Standard Deviation: 188.6

Change from BL at Day 8

124.0
cells/µL (Mean)
Standard Deviation: 148.8

Change from BL at FU

39.0
cells/µL (Mean)
Standard Deviation: 382.3

MAD Group V

Baseline (pre-dose Day 1)

1750.0
cells/µL (Mean)
Standard Deviation: 187.4

Change from BL at Day 3

390.0
cells/µL (Mean)
Standard Deviation: 297.4

Change from BL at Day 8

237.5
cells/µL (Mean)
Standard Deviation: 208.1

Change from BL at FU

262.5
cells/µL (Mean)
Standard Deviation: 220.2