Title

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GLWL-01
A 3-Part, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose, and Proof of Concept Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GLWL-01
  • Phase

    Phase 1
  • Study Type

    Interventional
  • Intervention/Treatment

    glwl-01 ...
  • Study Participants

    74
This 3-part study will explore the safety and tolerability of GLWL-01 in overweight/obese healthy participants after single doses (in Part A), and in participants with type 2 diabetes mellitus after multiple doses during a 28-day period (Parts B and C).
Study Started
Mar 31
2015
Primary Completion
Nov 09
2016
Study Completion
Nov 09
2016
Results Posted
Mar 21
2019
Last Update
Mar 21
2019

Drug GLWL-01, Part A

Capsules administered orally, in 2 out of 3 periods

Drug Placebo, Part A

Capsules administered orally in 1 out of 3 periods

Drug GLWL-01, Part B

Capsules administered orally either once or twice daily for 27 days, with a single dose on Day 28

Drug Placebo, Part B

Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28

Drug GLWL-01, Part C

Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28

Drug Placebo, Part C

Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28

GLWL-01, Part A Experimental

Escalating dose in at least 2 of 3 periods, starting at 10 milligrams (mg)

Placebo, Part A Placebo Comparator

Escalating dose of placebo to match GLWL-01, in 1 period

GLWL-01, Part B Experimental

Multiple ascending daily doses of GLWL-01 at up to six dose levels, based on Part A

Placebo, Part B Placebo Comparator

Multiple daily doses of placebo to match GLWL-01

GLWL-01, Part C Experimental

Multiple daily doses of GLWL-01 at level based upon Part B

Placebo, Part C Placebo Comparator

Multiple daily doses of placebo to match GLWL-01

Criteria

Inclusion Criteria:

PARTS A-C:

Non-vasectomized males (or those vasectomized less than 4 months prior to study start) must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug
Males agree to not donate sperm from dosing until 90 days after dosing
Laboratory test results within normal range or acceptable deviation, and Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) / Gamma Glutamyl Transferase (GGT) / Alkaline Phosphatase (ALP) to be less than or equal to (≤)1.5 x upper limit of normal (ULN), and total bilirubin has to be within normal limit
Estimated glomerular filtration rate (eGFR) greater than or equal to (≥) 60 milliliter (mL)/minute/1.73m2
No evidence of weight excursion beyond 5% of baseline weight within 3 months of screening

PART A Only:

Overtly healthy males or females, as determined by medical history and physical examination
Males must be 18 to 65 years old; females must be 40 to 65 years old

Female participants must be:

Women with prior history of hysterectomy who are at least 45 years of age and with follicle-stimulating hormone (FSH) greater than (>) 40 milli-international units per milliliter (mIU/mL), or
Menopausal women with either: spontaneous amenorrhea for at least 12 months (not induced by a medical condition or medications); or spontaneous amenorrhea for 6 to 12 months and a FSH > 40 mIU/mL
Body mass index (BMI) of 28 to 35 kilograms divided by height in meters squared (kg/m2)
Normotensive (supine systolic blood pressure (BP) less than (<) 140 millimeter of mercury (mmHg) and diastolic BP <90 mmHg
No evidence of weight excursion beyond 5% of baseline weight within 3 months of screening

PARTS B and C:

Must have Type 2 Diabetes Mellitus
Be 18 to 70 years old
Have BMI of 28 to 42 kg/m2
Female participants must be of non-childbearing potential, and must have undergone one of the following sterilization procedures at least 6 months prior to first dose: hysteroscopic sterilization, bilateral tubal ligation or bilateral salpingectomy, hysterectomy, or bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to the first dose and with FSH serum levels consistent with postmenopausal status
Normotensive (supine systolic BP) < 150 mmHg and diastolic BP <95 mmHg or well-controlled hypertension while on a stable hypertensive

Exclusion Criteria:

PARTS A-C:

Currently enrolled in a clinical trial or any other medical research judged to be not compatible with the study, or have participated in the last 30 days prior to dosing in a clinical trial involving an investigational product or non-approved use of a drug with short half-life, or within 5 half-lives of an investigational product with a half-life longer than 6 days
Abnormality in the 12-lead electrocardiogram (ECG) including corrected QT (QTc) interval with Bazett's correction >450 milliseconds (msec) for men and >470 msec for women, or an abnormality that, in the opinion of the Investigator, increases the risks associated with participating in the study
Significant cardiovascular disease or other disorders
Evidence of human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C, or other chronic liver or biliary disease
Average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or is unwilling to stop use of Cytochrome P450 (CYP3A) inhibitors/inducers (St. John's Wort) or alcohol consumption for the study, or regular use of known drugs of abuse or positive finding on urinary drug screen, use of cigarettes or nicotine products within last 3 months, or blood donation or loss within 56 days prior to the study
Neuropsychiatric disease or pharmacological therapy for such conditions within 1 year of dosing, or antidepressants or antipsychotics within 3 months of dosing, or surgery within last 60 days
Eating disorder or weight loss medications within 4 months of dosing, or bariatric surgery
Unsuitable for inclusion in the study in the opinion of the investigator or sponsor

PART A Only:

History of hypertension (or on treatment with any antihypertensives)
Endocrine illness such as diabetes, growth hormone insufficiency / acromegaly, adrenal gland or thyroid illness

PARTS B and C:

Currently taking simvastatin > 10 mg per day, or atorvastatin > 20 mg per day, or lovastatin >20 mg per day, or history of statin-induced myopathy / rhabdomyolysis. Participants taking any dose of simvastatin will be excluded from some cohorts
Allergic to the components of the Mixed Meal Tolerance Test

Summary

GLWL-01, Part A (10mg)

GLWL-01 Part A (50 mg)

GLWL-01 Part A (150 mg)

GLWL-01 Part A (300 mg)

GLWL-01 Part A (600 mg)

GLWL-01 Part A Placebo

GLWL-01 Part B (50 mg, Twice a Day)

GLWL-01 Part B (150 mg, Twice a Day)

GLWL-01 Part B (300 mg, Once a Day)

GLWL-01 Part B (450 mg, Once a Day)

GLWL-01 Part B (450 mg, Twice a Day)

GLWL-01 Part B (600 mg, Twice a Day)

GLWL-01 Part B Placebo

All Events

Event Type Organ System Event Term GLWL-01, Part A (10mg) GLWL-01 Part A (50 mg) GLWL-01 Part A (150 mg) GLWL-01 Part A (300 mg) GLWL-01 Part A (600 mg) GLWL-01 Part A Placebo GLWL-01 Part B (50 mg, Twice a Day) GLWL-01 Part B (150 mg, Twice a Day) GLWL-01 Part B (300 mg, Once a Day) GLWL-01 Part B (450 mg, Once a Day) GLWL-01 Part B (450 mg, Twice a Day) GLWL-01 Part B (600 mg, Twice a Day) GLWL-01 Part B Placebo

Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)

Treatment Emergent Adverse Event defined as an adverse event that started or worsened in severity at the time of, or after treatment

GLWL-01 Part B (50 mg, Twice a Day)

GLWL-01 Part B (150 mg, Twice a Day)

GLWL-01 Part B (300 mg, Once a Day)

GLWL-01 Part B (450 mg, Once a Day)

GLWL-01 Part B (450 mg, Twice a Day)

GLWL-01 Part B (600 mg, Twice a Day)

GLWL-01 Part B Placebo

Number of Participants With One or More Treatment Emergent Adverse Events (Part A)

Treatment Emergent Adverse Event defined as an adverse event that started or worsened in severity at the time of, or after treatment

GLWL-01 Part A (10mg)

GLWL-01 Part A (50 mg)

GLWL-01 Part A (150 mg)

GLWL-01 Part A (300 mg)

GLWL-01 Part A (600 mg)

GLWL-01 Part A Placebo

Fraction of Drug Excreted in the Urine (Fe) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

56.3
percentage of the drug (Mean)
Standard Deviation: 25.74

GLWL-01 Part B (150 mg, Twice a Day)

63.2
percentage of the drug (Mean)
Standard Deviation: 6.562

GLWL-01 Part B (300 mg, Once a Day)

41.5
percentage of the drug (Mean)
Standard Deviation: 11.15

GLWL-01 Part B (450 mg, Once a Day)

38.9
percentage of the drug (Mean)
Standard Deviation: 5.761

GLWL-01 Part B (450 mg, Twice a Day)

60.5
percentage of the drug (Mean)
Standard Deviation: 14.91

GLWL-01 Part B (600 mg, Twice a Day)

48.9
percentage of the drug (Mean)
Standard Deviation: 12.89

Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)

GLWL-01 Part B (50mg, Twice a Day)

22.53
mg/dL (Mean)
Standard Deviation: 23.0

GLWL-01 Part B (150 mg, Twice a Day)

7.38
mg/dL (Mean)
Standard Deviation: 40.4

GLWL-01 Part B (300 mg, Once a Day)

7.92
mg/dL (Mean)
Standard Deviation: 30.3

GLWL-01 Part B (450 mg, Once a Day)

21.39
mg/dL (Mean)
Standard Deviation: 13.5

GLWL-01, Part B (450 mg Twice a Day)

GLWL-01 Part B (600 mg, Twice a Day)

5.43
mg/dL (Mean)
Standard Deviation: 38.0

Placebo Part B

8.05
mg/dL (Mean)
Standard Deviation: 41.9

Time to Observed Cmax (Tmax) (Part A)

GLWL-01 Part A (10mg)

1.0
hours (Median)
Full Range: 0.999 to 1.02

GLWL-01 Part A (50 mg)

1.51
hours (Median)
Full Range: 0.476 to 4.5

GLWL-01 Part A (150 mg)

1.02
hours (Median)
Full Range: 0.466 to 4.55

GLWL-01 Part A (300 mg)

1.5
hours (Median)
Full Range: 1.0 to 4.5

GLWL-01 Part A (600 mg)

1.0
hours (Median)
Full Range: 0.998 to 6.0

Time to Observed Cmax (Tmax) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

2.0
hours (Median)
Full Range: 1.0 to 4.5

GLWL-01 Part B (150 mg, Twice a Day)

2.0
hours (Median)
Full Range: 2.0 to 4.5

GLWL-01 Part B (300 mg, Once a Day)

1.0
hours (Median)
Full Range: 0.99 to 2.0

GLWL-01 Part B (450 mg, Once a Day)

3.25
hours (Median)
Full Range: 0.999 to 6.0

GLWL-01 Part B (450 mg, Twice a Day)

2.0
hours (Median)
Full Range: 1.0 to 4.5

GLWL-01 Part B (600 mg, Twice a Day)

4.5
hours (Median)
Full Range: 2.0 to 4.5

Elimination Half-Life (T1/2) (Part A)

GLWL-01 Part A (10mg)

3.32
hours (Geometric Mean)
Geometric Coefficient of Variation: 8.8

GLWL-01 Part A (50 mg)

3.77
hours (Geometric Mean)
Geometric Coefficient of Variation: 23.9

GLWL-01 Part A (150 mg)

5.22
hours (Geometric Mean)
Geometric Coefficient of Variation: 25.3

GLWL-01 Part A (300 mg)

5.25
hours (Geometric Mean)
Geometric Coefficient of Variation: 25.8

GLWL-01 Part A (600 mg)

5.47
hours (Geometric Mean)
Geometric Coefficient of Variation: 19.0

Elimination Half-Life (T1/2) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

5.33
hours (Geometric Mean)
Geometric Coefficient of Variation: 12.1

GLWL-01 Part B (150 mg, Twice a Day)

6.16
hours (Geometric Mean)
Geometric Coefficient of Variation: 15.16

GLWL-01 Part B (300 mg, Once a Day)

5.24
hours (Geometric Mean)
Geometric Coefficient of Variation: 20.3

GLWL-01 Part B (450 mg, Once a Day)

5.94
hours (Geometric Mean)
Geometric Coefficient of Variation: 14.9

GLWL-01 Part B (450 mg, Twice a Day)

5.12
hours (Geometric Mean)
Geometric Coefficient of Variation: 18.5

GLWL-01 Part B (600 mg, Twice a Day)

6.26
hours (Geometric Mean)
Geometric Coefficient of Variation: 16.7

Apparent Clearance of Drug (CL/F) (Part A)

GLWL-01 Part A (10mg)

18.27
L/hr (Mean)
Standard Deviation: 3.17

GLWL-01 Part A (50 mg)

15.78
L/hr (Mean)
Standard Deviation: 2.18

GLWL-01 Part A (150 mg)

12.16
L/hr (Mean)
Standard Deviation: 4.16

GLWL-01 Part A (300 mg)

8.59
L/hr (Mean)
Standard Deviation: 1.37

GLWL-01 Part A (600 mg)

5.27
L/hr (Mean)
Standard Deviation: 1.77

Apparent Clearance of Drug (CL/F) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

11.4
L/hr (Mean)
Standard Deviation: 3.57

GLWL-01 Part B (150 mg, Twice a Day)

5.2
L/hr (Mean)
Standard Deviation: 1.14

GLWL-01 Part B (300 mg, Once a Day)

6.64
L/hr (Mean)
Standard Deviation: 1.10

GLWL-01 Part B (450 mg, Once a Day)

4.27
L/hr (Mean)
Standard Deviation: 1.35

GLWL-01 Part B (450 mg, Twice a Day)

3.23
L/hr (Mean)
Standard Deviation: 0.76

GLWL-01 Part B (600 mg, Twice a Day)

3.97
L/hr (Mean)
Standard Deviation: 1.36

Apparent Total Volume of Distribution (VZ/F) (Part A)

GLWL-01 Part A (10mg)

86.87
L (Mean)
Standard Deviation: 10.765

GLWL-01 Part A (50 mg)

86.35
L (Mean)
Standard Deviation: 15.326

GLWL-01 Part A (150 mg)

88.09
L (Mean)
Standard Deviation: 17.282

GLWL-01 Part A (300 mg)

66.97
L (Mean)
Standard Deviation: 20.368

GLWL-01 Part A (600 mg)

41.43
L (Mean)
Standard Deviation: 13.114

Apparent Total Volume of Distribution (VZ/F) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

89.6
L (Mean)
Standard Deviation: 39.15

GLWL-01 Part B (150 mg, Twice a Day)

46.3
L (Mean)
Standard Deviation: 10.18

GLWL-01 Part B (300 mg, Once a Day)

51.2
L (Mean)
Standard Deviation: 14.76

GLWL-01 Part B (450 mg, Once a Day)

36.8
L (Mean)
Standard Deviation: 12.39

GLWL-01 Part B (450 mg, Twice a Day)

24.2
L (Mean)
Standard Deviation: 7.055

GLWL-01 Part B (600 mg, Twice a Day)

35.8
L (Mean)
Standard Deviation: 12.01

Amount of Drug Excreted in Urine (Aet1-t12) (Part A)

Data Not Collected for this Parameter

GLWL-01 Part A (10mg)

GLWL-01 Part A (50 mg)

GLWL-01 Part A (150 mg)

GLWL-01 Part A (300 mg)

GLWL-01 Part A (600 mg)

GLWL-01 Part A Placebo

Amount of Drug Excreted in Urine (Aet1-t12) (Part B)

Data Not Collected for this Parameter

GLWL-01 Part B (50 mg, Twice a Day)

GLWL-01 Part B (150 mg, Twice a Day)

GLWL-01 Part B (300 mg, Once a Day)

GLWL-01 Part B (450 mg, Once a Day)

GLWL-01 Part B (450 mg, Twice a Day)

GLWL-01 Part B (600 mg, Twice a Day)

GLWL-01 Part B Placebo

Amount of Drug Excreted in Urine (Aet0-24) (Part A)

GLWL-01 Part A (10mg)

1.87
mg (Mean)
Standard Deviation: 0.611

GLWL-01 Part A (50 mg)

11.7
mg (Mean)
Standard Deviation: 2.56

GLWL-01 Part A (150 mg)

36.9
mg (Mean)
Standard Deviation: 12.1

GLWL-01 Part A (300 mg)

101.0
mg (Mean)
Standard Deviation: 15.2

GLWL-01 Part A (600 mg)

191.0
mg (Mean)
Standard Deviation: 37.4

Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part A)

GLWL-01 Part A (10mg)

0.5119
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 15.7

GLWL-01 Part A (50 mg)

3.138
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 13.7

GLWL-01 Part A (150 mg)

12.91
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 38.2

GLWL-01 Part A (300 mg)

35.16
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.9

GLWL-01 Part A (600 mg)

118.8
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 32.9

Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

5040.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 30.6

GLWL-01 Part B (150 mg, Twice a Day)

37000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 22.5

GLWL-01 Part B (300 mg, Once a Day)

47500.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 17.1

GLWL-01 Part B (450 mg, Once a Day)

124000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 41.9

GLWL-01 Part B (450 mg, Twice a Day)

202000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 26.6

GLWL-01 Part B (600 mg, Twice a Day)

235000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 39.2

Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Part A)

GLWL-01 Part A (10mg)

0.551
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.5

GLWL-01 Part A (50 mg)

3.15
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 11.6

GLWL-01 Part A (150 mg)

12.6
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 38.0

GLWL-01 Part A (300 mg)

34.4
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.9

GLWL-01 Part A (600 mg)

110.0
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 29.4

Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)

GLWL-01 Part B (50mg, Twice a Day)

5040.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 30.6

GLWL-01 Part B (150 mg, Twice a Day)

34600.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 21.7

GLWL-01 Part B (300 mg, Once a Day)

45700.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.9

GLWL-01 Part B (450 mg, Once a Day)

111000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 39.0

GLWL-01 Part B (450 mg, Twice a Day)

184000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 25.2

GLWL-01 Part B (600 mg, Twice a Day)

210000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 37.7

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part A)

GLWL-01 Part A (10mg)

0.555
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.7

GLWL-01 Part A (50 mg)

3.19
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 12.1

GLWL-01 Part A (150 mg)

13.0
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 41.2

GLWL-01 Part A (300 mg)

35.4
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 17.5

GLWL-01 Part A (600 mg)

119.0
µg*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 32.7

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

3150.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 20.1

GLWL-01 Part B (150 mg, Twice a Day)

13500.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 14.8

GLWL-01 Part B (300 mg, Once a Day)

31800.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 21.9

GLWL-01 Part B (450 mg, Once a Day)

69300.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 31.4

GLWL-01 Part B (450 mg, Twice a Day)

79000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 19.5

GLWL-01 Part B (600 mg, Twice a Day)

127000.0
ng*hr/mL (Geometric Mean)
Geometric Coefficient of Variation: 16.0

Maximum Observed Drug Concentration (Cmax) (Part A)

GLWL-01 Part A (10mg)

0.121
µg/mL (Geometric Mean)
Geometric Coefficient of Variation: 8.4

GLWL-01 Part A (50 mg)

0.6
µg/mL (Geometric Mean)
Geometric Coefficient of Variation: 35.4

GLWL-01 Part A (150 mg)

2.47
µg/mL (Geometric Mean)
Geometric Coefficient of Variation: 39.9

GLWL-01 Part A (300 mg)

5.08
µg/mL (Geometric Mean)
Geometric Coefficient of Variation: 17.6

GLWL-01 Part A (600 mg)

11.5
µg/mL (Geometric Mean)
Geometric Coefficient of Variation: 23.9

Maximum Observed Drug Concentration (Cmax) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

785.0
ng/mL (Geometric Mean)
Geometric Coefficient of Variation: 45.8

GLWL-01 Part B (150 mg, Twice a Day)

37.9
ng/mL (Geometric Mean)
Geometric Coefficient of Variation: 28.1

GLWL-01 Part B (300 mg, Once a Day)

62.8
ng/mL (Geometric Mean)
Geometric Coefficient of Variation: 10.6

GLWL-01 Part B (450 mg, Once a Day)

10800.0
ng/mL (Geometric Mean)
Geometric Coefficient of Variation: 31.5

GLWL-01 Part B (450 mg, Twice a Day)

16300.0
ng/mL (Geometric Mean)
Geometric Coefficient of Variation: 25.9

GLWL-01 Part B (600 mg, Twice a Day)

18200.0
ng/mL (Geometric Mean)
Geometric Coefficient of Variation: 33.7

Change From Baseline in Postprandial Glucose (Part B)

Mixed Meal Tolerance Test (4.5 hours after a meal on Day 28); Baseline Adjusted. The day 28 values were used for analysis; change from baseline was calculated on Day 28.

GLWL-01 Part B (50mg, Twice a Day)

18.8
mg/dL (Mean)
Standard Deviation: 11.70

GLWL-01 Part B (150 mg, Twice a Day)

11.6
mg/dL (Mean)
Standard Deviation: 27.74

GLWL-01 Part B (300 mg, Once a Day)

-13.7
mg/dL (Mean)
Standard Deviation: 33.16

GLWL-01 Part B (450 mg, Once a Day)

10.7
mg/dL (Mean)
Standard Deviation: 27.40

GLWL-01, Part B (450 mg, Twice a Day)

29.3
mg/dL (Mean)
Standard Deviation: 49.43

GLWL-01 Part B (600 mg, Twice a Day)

29.7
mg/dL (Mean)
Standard Deviation: 25.77

Placebo Part B

13.2
mg/dL (Mean)
Standard Deviation: 41.41

Change From Baseline in C-Peptide Concentration (Part B)

Mixed Meal Tolerance Test (4.5 hours after a meal on Day 28); Baseline-Adjusted. The day 28 values were used for analysis; change from baseline was calculated on Day 28.

GLWL-01 Part B (50mg, Twice a Day)

0.373
ng/mL (Mean)
Standard Deviation: 0.257

GLWL-01 Part B (150 mg, Twice a Day)

0.338
ng/mL (Mean)
Standard Deviation: 0.9523

GLWL-01 Part B (300 mg, Once a Day)

0.437
ng/mL (Mean)
Standard Deviation: 0.5171

GLWL-01 Part B (450 mg, Once a Day)

0.575
ng/mL (Mean)
Standard Deviation: 1.0658

GLWL-01, Part B (450 mg, Twice a Day)

0.36
ng/mL (Mean)
Standard Deviation: 1.3600

GLWL-01 Part B (600 mg, Twice a Day)

0.457
ng/mL (Mean)
Standard Deviation: 0.8498

Placebo Part B

0.043
ng/mL (Mean)
Standard Deviation: 0.6513

Change From Baseline in Insulin Concentration (Part B)

4.5 hours following Mixed Meal Tolerance Test (MMTT) on Day 28; Baseline Adjusted. The day 28 values were used for analysis; change from baseline was calculated on Day 28.

GLWL-01 Part B (50mg, Twice a Day)

-3.6
uU/mL (Mean)
Standard Deviation: 7.579

GLWL-01 Part B (150 mg, Twice a Day)

-3.89
uU/mL (Mean)
Standard Deviation: 11.533

GLWL-01 Part B (300 mg, Once a Day)

-9.75
uU/mL (Mean)
Standard Deviation: 10.687

GLWL-01 Part B (450 mg, Once a Day)

2.12
uU/mL (Mean)
Standard Deviation: 5.878

GLWL-01 Part B (450 mg, Twice a Day)

1.27
uU/mL (Mean)
Standard Deviation: 9.194

GLWL-01 Part B (600 mg, Twice a Day)

0.23
uU/mL (Mean)
Standard Deviation: 7.653

Placebo Part B

2.39
uU/mL (Mean)
Standard Deviation: 8.263

Fasting Glucose Concentration (Part B)

Fasting glucose concentration after 28 day treatment

GLWL-01 Part B (50mg, Twice a Day)

1.15
mmol/L (Mean)
Standard Deviation: 1.139

GLWL-01 Part B (150 mg, Twice a Day)

1.1
mmol/L (Mean)
Standard Deviation: 1.520

GLWL-01 Part B (300 mg, Once a Day)

-0.2
mmol/L (Mean)
Standard Deviation: 2.100

GLWL-01 Part B (450 mg, Once a Day)

0.63
mmol/L (Mean)
Standard Deviation: 0.299

GLWL-01 Part B (450 mg, Twice a Day)

-1.13
mmol/L (Mean)
Standard Deviation: 1.381

GLWL-01 Part B (600 mg, Twice a Day)

-0.1
mmol/L (Mean)
Standard Deviation: 2.104

Placebo Part B

0.91
mmol/L (Mean)
Standard Deviation: 2.116

Change From Baseline in Weight (Part B)

GLWL-01 Part B (50mg, Twice a Day)

-0.375
kilograms (kg) (Mean)
Standard Deviation: 0.763

GLWL-01 Part B (150 mg, Twice a Day)

-0.34
kilograms (kg) (Mean)
Standard Deviation: 0.786

GLWL-01 Part B (300 mg, Once a Day)

-0.15
kilograms (kg) (Mean)
Standard Deviation: 0.995

GLWL-01 Part B (450 mg, Once a Day)

-0.417
kilograms (kg) (Mean)
Standard Deviation: 0.741

GLWL-01 Part B (450 mg, Twice a Day)

0.417
kilograms (kg) (Mean)
Standard Deviation: 1.229

GLWL-01 Part B (600 mg, Twice a Day)

0.35
kilograms (kg) (Mean)
Standard Deviation: 0.356

Placebo Part B

-0.025
kilograms (kg) (Mean)
Standard Deviation: 0.717

Change From Baseline in Waist Circumference (Part B)

GLWL-01 Part B (50mg, Twice a Day)

-1.275
centimeters (Mean)
Standard Deviation: 3.522

GLWL-01 Part B (150 mg, Twice a Day)

1.36
centimeters (Mean)
Standard Deviation: 5.755

GLWL-01 Part B (300 mg, Once a Day)

-3.517
centimeters (Mean)
Standard Deviation: 4.001

GLWL-01 Part B (450 mg, Once a Day)

-1.383
centimeters (Mean)
Standard Deviation: 5.123

GLWL-01 Part B (450 mg, Twice a Day)

-1.25
centimeters (Mean)
Standard Deviation: 1.091

GLWL-01 Part B (600 mg, Twice a Day)

-0.083
centimeters (Mean)
Standard Deviation: 0.492

Placebo Part B

-0.867
centimeters (Mean)
Standard Deviation: 4.026

Amount of Drug Excreted in Urine (Aet0-24) (Part B)

GLWL-01 Part B (50mg, Twice a Day)

28.2
mg (Mean)
Standard Deviation: 12.87

GLWL-01 Part B (150 mg, Twice a Day)

94.8
mg (Mean)
Standard Deviation: 9.843

GLWL-01 Part B (300 mg, Once a Day)

125.0
mg (Mean)
Standard Deviation: 33.45

GLWL-01 Part B (450 mg, Once a Day)

175.0
mg (Mean)
Standard Deviation: 25.93

GLWL-01 Part B (450 mg, Twice a Day)

272.0
mg (Mean)
Standard Deviation: 67.08

GLWL-01 Part B (600 mg, Twice a Day)

293.0
mg (Mean)
Standard Deviation: 77.33

Change From Baseline in Hip Circumference (Part B)

GLWL-01 Part B (50mg, Twice a Day)

-1.05
centimeters (Mean)
Standard Deviation: 2.940

GLWL-01 Part B (150 mg, Twice a Day)

0.96
centimeters (Mean)
Standard Deviation: 7.442

GLWL-01 Part B (300 mg, Once a Day)

1.283
centimeters (Mean)
Standard Deviation: 2.337

GLWL-01 Part B (450 mg, Once a Day)

-0.417
centimeters (Mean)
Standard Deviation: 2.094

GLWL-01 Part B (450 mg, Twice a Day)

0.167
centimeters (Mean)
Standard Deviation: 0.753

GLWL-01 Part B (600 mg, Twice a Day)

-0.333
centimeters (Mean)
Standard Deviation: 0.516

Placebo Part B

0.192
centimeters (Mean)
Standard Deviation: 6.860

Fraction of Drug Excreted in the Urine (Fe) (Part A)

GLWL-01 Part A (50 mg)

23.3
percentage of the drug (Mean)
Standard Deviation: 5.13

GLWL-01 Part A (150 mg)

24.6
percentage of the drug (Mean)
Standard Deviation: 8.08

GLWL-01 Part A (300 mg)

33.6
percentage of the drug (Mean)
Standard Deviation: 5.07

GLWL-01 Part A (600 mg)

31.8
percentage of the drug (Mean)
Standard Deviation: 6.23

GLWL-01 Part A (10mg)

18.7
percentage of the drug (Mean)
Standard Deviation: 6.11

Total

74
Participants

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Sex: Female, Male

Part A First Treatment

GLWL-01, Part A (Placebo; 150 mg; 600 mg)

GLWL-01, Part A (10 mg; Placebo; 600 mg)

GLWL-01, Part A (10 mg; 150 mg; Placebo)

GLWL-01, Part A (Placebo; 300 mg; 1200 mg)

GLWL-01, Part A (50 mg, Placebo; 1200 mg)

GLWL-01, Part A ( 50 mg; 300 mg; Placebo)

Part A Second Treatment

GLWL-01, Part A (Placebo; 150 mg; 600 mg)

GLWL-01, Part A (10 mg; Placebo; 600 mg)

GLWL-01, Part A (10 mg; 150 mg; Placebo)

GLWL-01, Part A (Placebo; 300 mg; 1200 mg)

GLWL-01, Part A (50 mg, Placebo; 1200 mg)

GLWL-01, Part A ( 50 mg; 300 mg; Placebo)

Part A Third Treatment

GLWL-01, Part A (Placebo; 150 mg; 600 mg)

GLWL-01, Part A (10 mg; Placebo; 600 mg)

GLWL-01, Part A (10 mg; 150 mg; Placebo)

GLWL-01, Part A (Placebo; 300 mg; 1200 mg)

GLWL-01, Part A (50 mg, Placebo; 1200 mg)

GLWL-01, Part A ( 50 mg; 300 mg; Placebo)

Part B Overall

GLWL-01, Part B (50 mg, Twice a Day)

GLWL-01, Part B (150 mg Twice a Day)

GLWL-01, Part B (300 mg Once a Day)

GLWL-01, Part B (450 mg Once a Day)

GLWL-01, Part B, (450 mg Twice a Day)

GLWL-01, Part B (600 mg Twice a Day)

Placebo, Part B

Drop/Withdrawal Reasons

GLWL-01, Part A (Placebo; 300 mg; 1200 mg)

GLWL-01, Part A (50 mg, Placebo; 1200 mg)

GLWL-01, Part A ( 50 mg; 300 mg; Placebo)

GLWL-01, Part B (50 mg, Twice a Day)

GLWL-01, Part B (150 mg Twice a Day)

GLWL-01, Part B (450 mg Once a Day)

GLWL-01, Part B (600 mg Twice a Day)