Title

Dose Escalation Study of QR-010 in Homozygous ΔF508 Cystic Fibrosis Patients
Phase 1b, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of QR-010 in Subjects With Homozygous ΔF508 Cystic Fibrosis
  • Phase

    Phase 1/Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    qr-010 ...
  • Study Participants

    70
A randomized, double-blind, placebo-controlled study of single and multiple ascending doses of QR-010 in adults homozygous for ΔF508 Cystic Fibrosis.
The purpose of this study is to evaluate the safety, tolerability, and to determine the pharmacokinetics of QR-010 administered via inhalation in adult homozygous for ΔF508 Cystic Fibrosis.
Study Started
Jun 30
2015
Primary Completion
Sep 14
2017
Study Completion
Sep 14
2017
Results Posted
Feb 06
2019
Last Update
Feb 06
2019

Drug QR-010

Single-stranded RNA antisense oligonucleotide in aqueous solution for oral inhalaton

Drug Placebo

Normal Saline

QR-010 Experimental

QR-010 administered via inhalation either as a single dose or three times weekly for four weeks.

Placebo Placebo Comparator

Placebo (normal saline) administered via inhalation either as a single dose or three times weekly for four weeks.

Criteria

Inclusion Criteria:

Confirmed diagnosis of CF as defined by iontophoretic pilocarpine sweat chloride test (sweat chloride) of > 60 mmol/L
Confirmation of CFTR gene mutations homozygous for the ΔF508 mutation
Body mass index (BMI) ≥ 17 kg/m2
Non-smoking for a minimum of two years
FEV1 ≥70% of predicted normal for age, gender, and height, at Screening
Stable lung function
Adequate hepatic and renal function

Exclusion Criteria:

Breast-feeding or pregnant
Use of lumacaftor or ivacaftor
Use of any investigational drug or device
History of lung transplantation
Hemoptysis

Summary

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD

All Events

Event Type Organ System Event Term QR-010 SAD 6.25 mg QR-010 SAD 12.5 mg QR-010 SAD 25 mg QR-010 SAD 50 mg Placebo SAD QR-010 MAD 6.25 mg QR-010 MAD 12.5 mg QR-010 MAD 25 mg QR-010 MAD 50 mg Placebo MAD

Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study

Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD

Severity of Treatment Emergent Adverse Events From Baseline Through End of Study

Assessment of severity of treatment emergent adverse events (TEAEs). Severity is graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Modified for CF (CTCAE v4.03). For events not present in this listing the following grading was applied: Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Moderate: Minimal, local, or noninvasive intervention indicated; discomfort sufficient to reduce or interfere with daily activities; Severe: Medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization may be indicated; disabling; limits self-care with significant interference with daily activities; incapacitating with inability to perform self care activities of daily living; Life-threatening: Urgent intervention indicated; immediate risk of death.

QR-010 SAD 6.25 mg

Death

Life-Threatening

Mild

Moderate

Severe

QR-010 SAD 12.5 mg

Death

Life-Threatening

Mild

Moderate

Severe

QR-010 SAD 25 mg

Death

Life-Threatening

Mild

Moderate

Severe

QR-010 SAD 50 mg

Death

Life-Threatening

Mild

Moderate

Severe

Placebo SAD

Death

Life-Threatening

Mild

Moderate

Severe

QR-010 MAD 6.25 mg

Death

Life-Threatening

Mild

Moderate

Severe

QR-010 MAD 12.5 mg

Death

Life-Threatening

Mild

Moderate

Severe

QR-010 MAD 25 mg

Death

Life-Threatening

Mild

Moderate

Severe

QR-010 MAD 50 mg

Death

Life-Threatening

Mild

Moderate

Severe

Placebo MAD

Death

Life-Threatening

Mild

Moderate

Severe

Incidence of Subjects Experiencing Dose-Limiting Toxicities (DLT) in Each Dose Cohort From Baseline Through End of Study Visit.

DLT's were defined as an allergic reaction, acute bronchospasm or acute AEs of interest requiring (immediate) medical intervention.

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD

Terminal Half-life (T1/2)

The terminal elimination half-life will be estimated by non-linear regression analysis of the terminal elimination slope

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD

Area Under the Curve to Final Sample [AUC(0-last)]

Area under the curve to the final sample with a concentration greater than lower limit of quantification (LLQ) will be calculated using the linear trapezoidal method

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Dose 1

17.2
ng.hr/mL (Mean)
Standard Deviation: 8.2

Week 4, Dose 12

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Dose 1

19.0
ng.hr/mL (Mean)
Standard Deviation: 15.6

Week 4, Dose 12

17.0
ng.hr/mL (Mean)
Standard Deviation: 11.4

Placebo MAD

Area Under the Curve to Infinity [AUC(0-∞)]

AUC0-∞: Area under the curve to infinity will be calculated based on the last observed concentration Clast(obs) using formula: AUC0-∞=AUClast+Clast(obs)/λz

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD

Serum Clearance (CL)

CL: Serum clearance will be estimated using the formula: CL = Dose/AUC0-∞.

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD

Time to Maximum Serum Concentration

Tmax: Time to Cmax of QR-010 serum concentrations.

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Dose 1

0.6
hour (Median)
Full Range: 0.5 to 2.1

Week 4, Dose 12

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Dose 1

0.5
hour (Median)
Full Range: 0.5 to 3.0

Week 4, Dose 12

1.0
hour (Median)
Full Range: 1.0 to 2.0

Placebo MAD

Number of Subjects With Abnormalities Reported Regarding Laboratory Parameters, Vital Signs, ECG, Spirometry, and Physical Findings.

Number of subjects experiencing at least one abnormality for the categories laboratory parameters, vital signs, ECG, spirometry and physical findings that were reported as treatment emergent adverse event with a relationship to study drug as either possibly, probably or definitely.

QR-010 SAD 6.25 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

QR-010 SAD 12.5 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

QR-010 SAD 25 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

QR-010 SAD 50 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

Placebo SAD

ECG

laboratory parameters

physical findings

Spirometry

vital signs

QR-010 MAD 6.25 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

QR-010 MAD 12.5 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

QR-010 MAD 25 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

QR-010 MAD 50 mg

ECG

laboratory parameters

physical findings

Spirometry

vital signs

Placebo MAD

ECG

laboratory parameters

physical findings

Spirometry

vital signs

Maximum Serum Concentration

Cmax: QR-010 maximum serum concentrations

QR-010 SAD 6.25 mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Dose 1

2.9
ng/mL (Mean)
Standard Deviation: 1.2

Week 4, Dose 12

Placebo SAD

QR-010 MAD 6.25 mg

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Dose 1

4.53
ng/mL (Mean)
Standard Deviation: 3.38

Week 4, Dose 12

3.63
ng/mL (Mean)
Standard Deviation: 2.73

Placebo MAD

Adjusted Mean Change From Baseline in CFQ-R RSS

Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 15

-4.13
score on a scale (Mean)
Standard Error: 4.10

Day 33

6.43
score on a scale (Mean)
Standard Error: 4.92

Day 54

-10.24
score on a scale (Mean)
Standard Error: 6.56

QR-010 MAD 12.5 mg

Day 15

8.95
score on a scale (Mean)
Standard Error: 4.12

Day 33

12.65
score on a scale (Mean)
Standard Error: 4.93

Day 54

0.61
score on a scale (Mean)
Standard Error: 6.57

QR-010 MAD 25 mg

Day 15

7.76
score on a scale (Mean)
Standard Error: 4.15

Day 33

7.76
score on a scale (Mean)
Standard Error: 4.96

Day 54

5.91
score on a scale (Mean)
Standard Error: 6.59

QR-010 MAD 50 mg

Day 15

-0.8
score on a scale (Mean)
Standard Error: 4.51

Day 33

-3.02
score on a scale (Mean)
Standard Error: 5.40

Day 54

-4.13
score on a scale (Mean)
Standard Error: 7.20

Placebo MAD

Day 15

-5.09
score on a scale (Mean)
Standard Error: 3.59

Day 33

-6.48
score on a scale (Mean)
Standard Error: 4.29

Day 54

-10.31
score on a scale (Mean)
Standard Error: 5.87

Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo

Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 15

0.96
score on a scale (Mean)
Standard Error: 5.46

Day 33

12.91
score on a scale (Mean)
Standard Error: 6.53

Day 54

0.07
score on a scale (Mean)
Standard Error: 8.81

QR-010 MAD 12.5 mg

Day 15

14.03
score on a scale (Mean)
Standard Error: 5.49

Day 33

19.13
score on a scale (Mean)
Standard Error: 6.56

Day 54

10.92
score on a scale (Mean)
Standard Error: 8.83

QR-010 MAD 25 mg

Day 15

12.85
score on a scale (Mean)
Standard Error: 5.55

Day 33

14.24
score on a scale (Mean)
Standard Error: 6.60

Day 54

16.22
score on a scale (Mean)
Standard Error: 8.87

QR-010 MAD 50 mg

Day 15

4.29
score on a scale (Mean)
Standard Error: 5.73

Day 33

3.46
score on a scale (Mean)
Standard Error: 6.87

Day 54

6.18
score on a scale (Mean)
Standard Error: 9.26

Adjusted Mean Change From Baseline in CFQ-R RSS (Subgroup ppFEV1 <90% at Baseline)

Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 15

-3.37
score on a scale (Mean)
Standard Error: 5.51

Day 33

11.45
score on a scale (Mean)
Standard Error: 7.36

Day 54

-3.37
score on a scale (Mean)
Standard Error: 6.36

QR-010 MAD 12.5 mg

Day 15

8.64
score on a scale (Mean)
Standard Error: 4.87

Day 33

15.58
score on a scale (Mean)
Standard Error: 6.44

Day 54

5.86
score on a scale (Mean)
Standard Error: 5.59

QR-010 MAD 25 mg

Day 15

9.56
score on a scale (Mean)
Standard Error: 4.28

Day 33

8.44
score on a scale (Mean)
Standard Error: 5.71

Day 54

7.33
score on a scale (Mean)
Standard Error: 4.94

QR-010 MAD 50 mg

Day 15

-0.87
score on a scale (Mean)
Standard Error: 4.79

Day 33

-0.87
score on a scale (Mean)
Standard Error: 6.38

Day 54

-3.65
score on a scale (Mean)
Standard Error: 5.52

Placebo MAD

Day 15

-4.77
score on a scale (Mean)
Standard Error: 4.82

Day 33

-11.72
score on a scale (Mean)
Standard Error: 6.41

Day 54

-6.49
score on a scale (Mean)
Standard Error: 6.33

Adjusted Mean Change From Baseline in CFQ-R RSS as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline)

Patient Reported Outcome measure Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS). A higher score represents a better outcome. A minimal clinically important difference (MCID) in the respiratory domain (CFQ-R RSS) has been established in stable populations as 4.0 points, and a maximum score is 100 points. Mean values reported refer to ''difference vs placebo in adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 15

1.41
score on a scale (Mean)
Standard Error: 7.29

Day 33

23.17
score on a scale (Mean)
Standard Error: 9.73

Day 54

3.12
score on a scale (Mean)
Standard Error: 8.93

QR-010 MAD 12.5 mg

Day 15

13.41
score on a scale (Mean)
Standard Error: 6.95

Day 33

27.3
score on a scale (Mean)
Standard Error: 9.17

Day 54

12.35
score on a scale (Mean)
Standard Error: 8.58

QR-010 MAD 25 mg

Day 15

14.33
score on a scale (Mean)
Standard Error: 6.49

Day 33

20.16
score on a scale (Mean)
Standard Error: 8.62

Day 54

13.82
score on a scale (Mean)
Standard Error: 8.08

QR-010 MAD 50 mg

Day 15

3.9
score on a scale (Mean)
Standard Error: 6.74

Day 33

10.84
score on a scale (Mean)
Standard Error: 9.01

Day 54

2.84
score on a scale (Mean)
Standard Error: 8.33

Adjusted Mean Change From Baseline in ppFEV1

Exploratory efficacy parameter, as measured by spirometry, and expressed in percent predicted FEV1 (ppFEV1). Mean values reported refer to ''adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 33

1.54
percentage of predicted (Mean)
Standard Error: 2.40

Day 54

1.68
percentage of predicted (Mean)
Standard Error: 2.88

(pre-dose) Day 15

0.06
percentage of predicted (Mean)
Standard Error: 1.96

(pre-dose) Day 26

0.46
percentage of predicted (Mean)
Standard Error: 2.64

QR-010 MAD 12.5 mg

Day 33

0.05
percentage of predicted (Mean)
Standard Error: 2.40

Day 54

-1.63
percentage of predicted (Mean)
Standard Error: 2.88

(pre-dose) Day 15

2.5
percentage of predicted (Mean)
Standard Error: 1.96

(pre-dose) Day 26

3.22
percentage of predicted (Mean)
Standard Error: 2.64

QR-010 MAD 25 mg

Day 33

-2.17
percentage of predicted (Mean)
Standard Error: 2.40

Day 54

0.61
percentage of predicted (Mean)
Standard Error: 2.88

(pre-dose) Day 15

-4.03
percentage of predicted (Mean)
Standard Error: 1.96

(pre-dose) Day 26

-0.98
percentage of predicted (Mean)
Standard Error: 2.64

QR-010 MAD 50 mg

Day 33

-3.21
percentage of predicted (Mean)
Standard Error: 2.63

Day 54

-2.43
percentage of predicted (Mean)
Standard Error: 3.15

(pre-dose) Day 15

-1.85
percentage of predicted (Mean)
Standard Error: 2.14

(pre-dose) Day 26

-1.39
percentage of predicted (Mean)
Standard Error: 2.89

Placebo MAD

Day 33

-2.7
percentage of predicted (Mean)
Standard Error: 2.08

Day 54

-2.58
percentage of predicted (Mean)
Standard Error: 2.49

(pre-dose) Day 15

-0.83
percentage of predicted (Mean)
Standard Error: 1.70

(pre-dose) Day 26

-0.8
percentage of predicted (Mean)
Standard Error: 2.28

Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo

Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1 (ppFEV1). Mean values reported refer to''difference vs placebo in adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 15

0.89
percentage of predicted (Mean)
Standard Error: 2.59

Day 26

1.26
percentage of predicted (Mean)
Standard Error: 3.49

Day 33

4.24
percentage of predicted (Mean)
Standard Error: 3.18

Day 54

4.26
percentage of predicted (Mean)
Standard Error: 3.81

QR-010 MAD 12.5 mg

Day 15

3.32
percentage of predicted (Mean)
Standard Error: 2.59

Day 26

4.02
percentage of predicted (Mean)
Standard Error: 3.49

Day 33

2.75
percentage of predicted (Mean)
Standard Error: 3.18

Day 54

0.96
percentage of predicted (Mean)
Standard Error: 3.80

QR-010 MAD 25 mg

Day 15

-3.2
percentage of predicted (Mean)
Standard Error: 2.59

Day 26

-0.17
percentage of predicted (Mean)
Standard Error: 3.49

Day 33

0.53
percentage of predicted (Mean)
Standard Error: 3.18

Day 54

3.2
percentage of predicted (Mean)
Standard Error: 3.81

QR-010 MAD 50 mg

Day 15

-1.02
percentage of predicted (Mean)
Standard Error: 2.73

Day 26

-0.59
percentage of predicted (Mean)
Standard Error: 3.68

Day 33

-0.51
percentage of predicted (Mean)
Standard Error: 3.35

Day 54

0.15
percentage of predicted (Mean)
Standard Error: 4.01

Adjusted Mean Change From Baseline in ppFEV1 (Subgroup ppFEV1 <90% at Baseline)

Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1. Mean values reported refer to ''adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 15

-0.29
percentage of predicted (Mean)
Standard Error: 2.22

Day 26

4.21
percentage of predicted (Mean)
Standard Error: 4.05

Day 33

6.01
percentage of predicted (Mean)
Standard Error: 3.16

QR-010 MAD 12.5 mg

Day 15

4.54
percentage of predicted (Mean)
Standard Error: 1.92

Day 26

7.15
percentage of predicted (Mean)
Standard Error: 3.51

Day 33

3.81
percentage of predicted (Mean)
Standard Error: 2.74

QR-010 MAD 25 mg

Day 15

-3.45
percentage of predicted (Mean)
Standard Error: 1.71

Day 26

0.89
percentage of predicted (Mean)
Standard Error: 3.13

Day 33

-0.68
percentage of predicted (Mean)
Standard Error: 2.44

QR-010 MAD 50 mg

Day 15

-1.01
percentage of predicted (Mean)
Standard Error: 1.91

Day 26

-0.1
percentage of predicted (Mean)
Standard Error: 3.50

Day 33

-0.97
percentage of predicted (Mean)
Standard Error: 2.73

Placebo MAD

Day 15

-3.4
percentage of predicted (Mean)
Standard Error: 1.95

Day 26

-3.76
percentage of predicted (Mean)
Standard Error: 3.52

Day 33

-4.18
percentage of predicted (Mean)
Standard Error: 2.76

Adjusted Mean Change From Baseline in ppFEV1 as Compared to Placebo (Subgroup ppFEV1 <90% at Baseline)

Exploratory efficacy parameter, as measured by spirometry, and expresssed in percent predicted FEV1. Mean values reported refer to ''difference vs placebo in adjusted mean change from baseline'' values.

QR-010 MAD 6.25 mg

Day 15

3.11
percentage of predicted (Mean)
Standard Error: 2.99

Day 26

7.97
percentage of predicted (Mean)
Standard Error: 5.39

Day 33

10.19
percentage of predicted (Mean)
Standard Error: 4.22

QR-010 MAD 12.5 mg

Day 15

7.93
percentage of predicted (Mean)
Standard Error: 2.76

Day 26

10.9
percentage of predicted (Mean)
Standard Error: 4.98

Day 33

7.99
percentage of predicted (Mean)
Standard Error: 3.91

QR-010 MAD 25 mg

Day 15

-0.05
percentage of predicted (Mean)
Standard Error: 2.59

Day 26

4.65
percentage of predicted (Mean)
Standard Error: 4.71

Day 33

3.5
percentage of predicted (Mean)
Standard Error: 3.69

QR-010 MAD 50 mg

Day 15

2.38
percentage of predicted (Mean)
Standard Error: 2.74

Day 26

3.65
percentage of predicted (Mean)
Standard Error: 4.97

Day 33

3.21
percentage of predicted (Mean)
Standard Error: 3.89

Total

70
Participants

Age, Continuous

25.6
years (Mean)
Standard Deviation: 7.35

BMI

22.3
kg/m2 (Mean)
Standard Deviation: 2.42

FEV1

3.32
L (Mean)
Standard Deviation: 0.792

ppFEV1

88.8
percent (Mean)
Standard Deviation: 14.54

Weight (kg)

63.0
kg (Mean)
Standard Deviation: 9.11

Age, Categorical

Race (NIH/OMB)

Region of Enrollment

Sex: Female, Male

Single Ascending Dose (SAD) Cohorts

QR-010 SAD 6.25mg

QR-010 SAD 12.5 mg

QR-010 SAD 25 mg

QR-010 SAD 50 mg

Placebo SAD

Multiple Ascending Dose (MAD) Cohorst

QR-010 MAD 6.25

QR-010 MAD 12.5 mg

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD

Drop/Withdrawal Reasons

QR-010 MAD 25 mg

QR-010 MAD 50 mg

Placebo MAD