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

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02377362

Enrollment

Registered

2015-03-03

Start date

2015-03-31

Completion date

2016-11-09

Last updated

2019-03-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Brief summary

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).

Interventions

DRUGGLWL-01, Part A

Capsules administered orally, in 2 out of 3 periods

DRUGPlacebo, Part A

Capsules administered orally in 1 out of 3 periods

DRUGGLWL-01, Part B

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

DRUGPlacebo, Part B

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

DRUGGLWL-01, Part C

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

DRUGPlacebo, Part C

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Yes

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: 1. 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 2. 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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With One or More Treatment Emergent Adverse Events (Part A)	Baseline to 7 weeks	Treatment Emergent Adverse Event defined as an adverse event that started or worsened in severity at the time of, or after treatment
Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	Baseline to 6 weeks	Treatment Emergent Adverse Event defined as an adverse event that started or worsened in severity at the time of, or after treatment

Secondary

Measure	Time frame	Description
Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Part A)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24 hours post-dose	—
Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24 hours post dose starting on Day 28	—
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part A)	Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose	—
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting Day 1	—
Maximum Observed Drug Concentration (Cmax) (Part A)	Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose	—
Maximum Observed Drug Concentration (Cmax) (Part B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28	—
Time to Observed Cmax (Tmax) (Part A)	Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose	—
Time to Observed Cmax (Tmax) (Part B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28	—
Elimination Half-Life (T1/2) (Part A)	Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose	—
Elimination Half-Life (T1/2) (Part B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28	—
Apparent Clearance of Drug (CL/F) (Part A)	Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose	—
Apparent Clearance of Drug (CL/F) (Part B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28	—
Apparent Total Volume of Distribution (VZ/F) (Part A)	Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose	—
Apparent Total Volume of Distribution (VZ/F) (Part B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28	—
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part A)	Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose	—
Amount of Drug Excreted in Urine (Aet1-t12) (Part B)	Pre-Dose and 12 hours Post-Dose on Day 28	Data Not Collected for this Parameter
Amount of Drug Excreted in Urine (Aet0-24) (Part A)	Pre-Dose and 24-hours Post-Dose	—
Amount of Drug Excreted in Urine (Aet0-24) (Part B)	Pre-Dose and 24-hours Post-Dose on Day 28	—
Fraction of Drug Excreted in the Urine (Fe) (Part A)	Pre-Dose and 24-hours Post-Dose	—
Fraction of Drug Excreted in the Urine (Fe) (Part B)	Pre-Dose and 24-hours Post-Dose on Day 28	—
Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)	Baseline to Day 24-26	—
Change From Baseline in Postprandial Glucose (Part B)	Day 28	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.
Change From Baseline in C-Peptide Concentration (Part B)	Day 28	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.
Change From Baseline in Insulin Concentration (Part B)	Day 28	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.
Fasting Glucose Concentration (Part B)	Baseline to Day 28	Fasting glucose concentration after 28 day treatment
Change From Baseline in Weight (Part B)	Baseline to Day 28	—
Change From Baseline in Waist Circumference (Part B)	Baseline to Day 28	—
Change From Baseline in Hip Circumference (Part B)	Baseline to Day 28	—
Amount of Drug Excreted in Urine (Aet1-t12) (Part A)	Pre-Dose and 12 hours Post-Dose	Data Not Collected for this Parameter
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)	Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28	—

Countries

United States

Participant flow

Pre-assignment details

Part A was a 3-period crossover design. Part A participants were to receive 2 escalating single doses of study drug and one dose of placebo. Part B participants were randomized to multiple doses of study drug or placebo. The study was stopped after Part B.

Participants by arm

Arm	Count
GLWL-01, Part A (Placebo; 150 mg; 600 mg) Part A: Cohort 1(C1) Sequence 1 (Placebo, 150 mg, 600 mg) Placebo was taken orally first intervention, then 150 mg GLWL 01 was taken orally second intervention, then 600 mg GLWL 01 was taken orally third intervention	4
GLWL-01, Part A (10 mg; Placebo; 600 mg) Part A: Cohort 1(C1) Sequence 2 (10 mg, Placebo, 600 mg) 10 mg GLWL 01 was taken orally first intervention, then Placebo was taken orally second intervention, then 600 mg GLWL 01 was taken orally third intervention.	4
GLWL-01, Part A (10 mg; 150 mg; Placebo) Part A: Cohort 1(C1) Sequence 3 (10 mg, 150 mg, Placebo) 10 mg GLWL 01 was taken orally first intervention, then 150 mg GLWL 01 was taken orally second intervention, then Placebo was taken orally third intervention	4
GLWL-01, Part A (Placebo; 300 mg; 1200 mg) Part A: Cohort 2(C2) Sequence 1 (Placebo, 300 mg, 1200 mg) Placebo was taken orally first intervention, then 300 mg GLWL 01 was taken orally second intervention, then 1200 mg GLWL 01 was taken orally third intervention	4
GLWL-01 Part A (50 mg, Placebo; 1200 mg) Part A: Cohort 2(C2) Sequence 2 (50 mg, Placebo, 1200 mg) 50 mg GLWL 01 was taken orally first intervention, then Placebo was taken orally second intervention, then 1200 mg GLWL 01 was taken orally third intervention	4
GLWL-01, Part A ( 50 mg; 300 mg; Placebo) Part A: Cohort 2(C3) Sequence 3 (50 mg, 300 mg, Placebo) 50 mg GLWL 01 was taken orally first intervention, then 300 mg GLWL 01 was taken orally second intervention, then Placebo was taken orally third intervention	4
GLWL-01, Part B (50 mg Twice a Day) Multiple oral doses Part B: Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28	6
GLWL-01, Part B (150 mg Twice a Day) Multiple oral doses Part B: Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28	6
GLWL-01, Part B (300 mg Once a Day) Multiple oral doses Part B: Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28	6
GLWL-01, Part B (450 mg Once a Day) Multiple oral doses Part B: Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28	7
GLWL-01, Part B (450 mg Twice a Day) Multiple oral doses Part B: Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28	6
GLWL-01, Part B (600 mg Twice a Day) Multiple oral doses Part B: Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28	7
Placebo, Part B Multiple daily doses of placebo to match GLWL-01 Placebo, Part B: Capsules administered orally either once or twice daily for 27 days with a single dose on Day 28	12
Total	74

Withdrawals & dropouts

Period	Reason	FG003	FG004	FG005	FG006	FG007	FG009	FG011
Part A Second Treatment	Protocol Violation	0	1	0	0	0	0	0
Part A Third Treatment	Highest dose level 1200 not used	4	3	4	0	0	0	0
Part B Overall	Adverse Event	0	0	0	1	1	0	0
Part B Overall	Protocol Violation	0	0	0	0	0	1	0
Part B Overall	Withdrawal by Subject	0	0	0	1	0	0	1

Baseline characteristics

Characteristic	Total	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)	GLWL-01, Part B (50 mg Twice a Day)	GLWL-01, Part A (Placebo; 150 mg; 600 mg)	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
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	8 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	2 Participants	1 Participants	2 Participants
Age, Categorical Between 18 and 65 years	66 Participants	4 Participants	4 Participants	4 Participants	4 Participants	4 Participants	6 Participants	4 Participants	5 Participants	6 Participants	5 Participants	4 Participants	6 Participants	10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	56 Participants	1 Participants	1 Participants	3 Participants	2 Participants	4 Participants	4 Participants	2 Participants	4 Participants	5 Participants	5 Participants	6 Participants	7 Participants	12 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants	3 Participants	3 Participants	1 Participants	2 Participants	0 Participants	2 Participants	2 Participants	2 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	5 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	66 Participants	3 Participants	3 Participants	3 Participants	4 Participants	4 Participants	5 Participants	4 Participants	4 Participants	6 Participants	7 Participants	6 Participants	6 Participants	11 Participants
Region of Enrollment United States	74 Participants	4 Participants	4 Participants	4 Participants	4 Participants	4 Participants	6 Participants	4 Participants	6 Participants	6 Participants	7 Participants	6 Participants	7 Participants	12 Participants
Sex: Female, Male Female	27 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	2 Participants	2 Participants	2 Participants	3 Participants	4 Participants	4 Participants	8 Participants
Sex: Female, Male Male	47 Participants	4 Participants	4 Participants	3 Participants	4 Participants	4 Participants	5 Participants	2 Participants	4 Participants	4 Participants	4 Participants	2 Participants	3 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8	0 / 8	0 / 8	0 / 8	0 / 19	0 / 6	0 / 6	0 / 6	0 / 7	0 / 6	0 / 7	0 / 12
other Total, other adverse events	1 / 8	2 / 8	0 / 8	2 / 8	3 / 8	9 / 19	5 / 6	5 / 6	3 / 6	5 / 7	4 / 6	7 / 7	6 / 12
serious Total, serious adverse events	0 / 8	0 / 8	0 / 8	0 / 8	0 / 8	0 / 19	0 / 6	0 / 6	0 / 6	0 / 7	0 / 6	0 / 7	0 / 12

Outcome results

Primary

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

Time frame: Baseline to 7 weeks

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GLWL-01 Part A (10mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Part A)	1 Participants
GLWL-01 Part A (50 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Part A)	2 Participants
GLWL-01 Part A (150 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Part A)	0 Participants
GLWL-01 Part A (300 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Part A)	2 Participants
GLWL-01 Part A (600 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Part A)	3 Participants
GLWL-01 Part A Placebo	Number of Participants With One or More Treatment Emergent Adverse Events (Part A)	9 Participants

Primary

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

Time frame: Baseline to 6 weeks

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
GLWL-01 Part A (10mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	5 Participants
GLWL-01 Part A (50 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	5 Participants
GLWL-01 Part A (150 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	3 Participants
GLWL-01 Part A (300 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	5 Participants
GLWL-01 Part A (600 mg)	Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	4 Participants
GLWL-01 Part A Placebo	Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	7 Participants
GLWL-01 Part B Placebo	Number of Participants With One or More Treatment Emergent Adverse Events (Parts B)	6 Participants

Secondary

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

Time frame: Pre-Dose and 24-hours Post-Dose

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part A)	1.87 mg	Standard Deviation 0.611
GLWL-01 Part A (50 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part A)	11.7 mg	Standard Deviation 2.56
GLWL-01 Part A (150 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part A)	36.9 mg	Standard Deviation 12.1
GLWL-01 Part A (300 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part A)	101 mg	Standard Deviation 15.2
GLWL-01 Part A (600 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part A)	191 mg	Standard Deviation 37.4

Secondary

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

Time frame: Pre-Dose and 24-hours Post-Dose on Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part B)	28.2 mg	Standard Deviation 12.87
GLWL-01 Part A (50 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part B)	94.8 mg	Standard Deviation 9.843
GLWL-01 Part A (150 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part B)	125 mg	Standard Deviation 33.45
GLWL-01 Part A (300 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part B)	175 mg	Standard Deviation 25.93
GLWL-01 Part A (600 mg)	Amount of Drug Excreted in Urine (Aet0-24) (Part B)	272 mg	Standard Deviation 67.08
GLWL-01 Part A Placebo	Amount of Drug Excreted in Urine (Aet0-24) (Part B)	293 mg	Standard Deviation 77.33

Secondary

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

Data Not Collected for this Parameter

Time frame: Pre-Dose and 12 hours Post-Dose

Population: Data were not collected

Secondary

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

Data Not Collected for this Parameter

Time frame: Pre-Dose and 12 hours Post-Dose on Day 28

Population: Data were not collected

Secondary

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

Time frame: Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Apparent Clearance of Drug (CL/F) (Part A)	18.27 L/hr	Standard Deviation 3.17
GLWL-01 Part A (50 mg)	Apparent Clearance of Drug (CL/F) (Part A)	15.78 L/hr	Standard Deviation 2.18
GLWL-01 Part A (150 mg)	Apparent Clearance of Drug (CL/F) (Part A)	12.16 L/hr	Standard Deviation 4.16
GLWL-01 Part A (300 mg)	Apparent Clearance of Drug (CL/F) (Part A)	8.59 L/hr	Standard Deviation 1.37
GLWL-01 Part A (600 mg)	Apparent Clearance of Drug (CL/F) (Part A)	5.27 L/hr	Standard Deviation 1.77

Secondary

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

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Apparent Clearance of Drug (CL/F) (Part B)	11.4 L/hr	Standard Deviation 3.57
GLWL-01 Part A (50 mg)	Apparent Clearance of Drug (CL/F) (Part B)	5.20 L/hr	Standard Deviation 1.14
GLWL-01 Part A (150 mg)	Apparent Clearance of Drug (CL/F) (Part B)	6.64 L/hr	Standard Deviation 1.1
GLWL-01 Part A (300 mg)	Apparent Clearance of Drug (CL/F) (Part B)	4.27 L/hr	Standard Deviation 1.35
GLWL-01 Part A (600 mg)	Apparent Clearance of Drug (CL/F) (Part B)	3.23 L/hr	Standard Deviation 0.76
GLWL-01 Part A Placebo	Apparent Clearance of Drug (CL/F) (Part B)	3.97 L/hr	Standard Deviation 1.36

Secondary

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

Time frame: Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Apparent Total Volume of Distribution (VZ/F) (Part A)	86.87 L	Standard Deviation 10.765
GLWL-01 Part A (50 mg)	Apparent Total Volume of Distribution (VZ/F) (Part A)	86.35 L	Standard Deviation 15.326
GLWL-01 Part A (150 mg)	Apparent Total Volume of Distribution (VZ/F) (Part A)	88.09 L	Standard Deviation 17.282
GLWL-01 Part A (300 mg)	Apparent Total Volume of Distribution (VZ/F) (Part A)	66.97 L	Standard Deviation 20.368
GLWL-01 Part A (600 mg)	Apparent Total Volume of Distribution (VZ/F) (Part A)	41.43 L	Standard Deviation 13.114

Secondary

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

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Apparent Total Volume of Distribution (VZ/F) (Part B)	89.6 L	Standard Deviation 39.15
GLWL-01 Part A (50 mg)	Apparent Total Volume of Distribution (VZ/F) (Part B)	46.3 L	Standard Deviation 10.18
GLWL-01 Part A (150 mg)	Apparent Total Volume of Distribution (VZ/F) (Part B)	51.2 L	Standard Deviation 14.76
GLWL-01 Part A (300 mg)	Apparent Total Volume of Distribution (VZ/F) (Part B)	36.8 L	Standard Deviation 12.39
GLWL-01 Part A (600 mg)	Apparent Total Volume of Distribution (VZ/F) (Part B)	24.2 L	Standard Deviation 7.055
GLWL-01 Part A Placebo	Apparent Total Volume of Distribution (VZ/F) (Part B)	35.8 L	Standard Deviation 12.01

Secondary

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

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Part A)	0.551 µg*hr/mL	Geometric Coefficient of Variation 16.5
GLWL-01 Part A (50 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Part A)	3.15 µg*hr/mL	Geometric Coefficient of Variation 11.6
GLWL-01 Part A (150 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Part A)	12.6 µg*hr/mL	Geometric Coefficient of Variation 38
GLWL-01 Part A (300 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Part A)	34.4 µg*hr/mL	Geometric Coefficient of Variation 16.9
GLWL-01 Part A (600 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Part A)	110 µg*hr/mL	Geometric Coefficient of Variation 29.4

Secondary

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

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24 hours post dose starting on Day 28

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)	5040 ng*hr/mL	Geometric Coefficient of Variation 30.6
GLWL-01 Part A (50 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)	34600 ng*hr/mL	Geometric Coefficient of Variation 21.7
GLWL-01 Part A (150 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)	45700 ng*hr/mL	Geometric Coefficient of Variation 16.9
GLWL-01 Part A (300 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)	111000 ng*hr/mL	Geometric Coefficient of Variation 39
GLWL-01 Part A (600 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)	184000 ng*hr/mL	Geometric Coefficient of Variation 25.2
GLWL-01 Part A Placebo	Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) (Parts B)	210000 ng*hr/mL	Geometric Coefficient of Variation 37.7

Secondary

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

Time frame: Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part A)	0.555 µg*hr/mL	Geometric Coefficient of Variation 16.7
GLWL-01 Part A (50 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part A)	3.19 µg*hr/mL	Geometric Coefficient of Variation 12.1
GLWL-01 Part A (150 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part A)	13.0 µg*hr/mL	Geometric Coefficient of Variation 41.2
GLWL-01 Part A (300 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part A)	35.4 µg*hr/mL	Geometric Coefficient of Variation 17.5
GLWL-01 Part A (600 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part A)	119 µg*hr/mL	Geometric Coefficient of Variation 32.7

Secondary

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

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting Day 1

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)	3150 ng*hr/mL	Geometric Coefficient of Variation 20.1
GLWL-01 Part A (50 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)	13500 ng*hr/mL	Geometric Coefficient of Variation 14.8
GLWL-01 Part A (150 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)	31800 ng*hr/mL	Geometric Coefficient of Variation 21.9
GLWL-01 Part A (300 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)	69300 ng*hr/mL	Geometric Coefficient of Variation 31.4
GLWL-01 Part A (600 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)	79000 ng*hr/mL	Geometric Coefficient of Variation 19.5
GLWL-01 Part A Placebo	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) (Part B)	127000 ng*hr/mL	Geometric Coefficient of Variation 16

Secondary

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

Time frame: Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part A)	0.5119 µg*hr/mL	Geometric Coefficient of Variation 15.7
GLWL-01 Part A (50 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part A)	3.138 µg*hr/mL	Geometric Coefficient of Variation 13.7
GLWL-01 Part A (150 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part A)	12.91 µg*hr/mL	Geometric Coefficient of Variation 38.2
GLWL-01 Part A (300 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part A)	35.16 µg*hr/mL	Geometric Coefficient of Variation 16.9
GLWL-01 Part A (600 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part A)	118.8 µg*hr/mL	Geometric Coefficient of Variation 32.9

Secondary

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

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)	5040 ng*hr/mL	Geometric Coefficient of Variation 30.6
GLWL-01 Part A (50 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)	37000 ng*hr/mL	Geometric Coefficient of Variation 22.5
GLWL-01 Part A (150 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)	47500 ng*hr/mL	Geometric Coefficient of Variation 17.1
GLWL-01 Part A (300 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)	124000 ng*hr/mL	Geometric Coefficient of Variation 41.9
GLWL-01 Part A (600 mg)	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)	202000 ng*hr/mL	Geometric Coefficient of Variation 26.6
GLWL-01 Part A Placebo	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) (Part B)	235000 ng*hr/mL	Geometric Coefficient of Variation 39.2

Secondary

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

Time frame: Baseline to Day 24-26

Population: The 450 mg twice a day arm had no usable continuous glucose data, due to technical difficulties

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)	22.53 mg/dL	Standard Deviation 23
GLWL-01 Part A (50 mg)	Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)	7.38 mg/dL	Standard Deviation 40.4
GLWL-01 Part A (150 mg)	Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)	7.92 mg/dL	Standard Deviation 30.3
GLWL-01 Part A (300 mg)	Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)	21.39 mg/dL	Standard Deviation 13.5
GLWL-01 Part A Placebo	Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)	5.43 mg/dL	Standard Deviation 38
GLWL-01 Part B Placebo	Change From Baseline in Average Plasma Glucose Concentration After Multiple Doses (Part B)	8.05 mg/dL	Standard Deviation 41.9

Secondary

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.

Time frame: Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Change From Baseline in C-Peptide Concentration (Part B)	0.373 ng/mL	Standard Deviation 0.257
GLWL-01 Part A (50 mg)	Change From Baseline in C-Peptide Concentration (Part B)	0.338 ng/mL	Standard Deviation 0.9523
GLWL-01 Part A (150 mg)	Change From Baseline in C-Peptide Concentration (Part B)	0.437 ng/mL	Standard Deviation 0.5171
GLWL-01 Part A (300 mg)	Change From Baseline in C-Peptide Concentration (Part B)	0.575 ng/mL	Standard Deviation 1.0658
GLWL-01 Part A (600 mg)	Change From Baseline in C-Peptide Concentration (Part B)	0.360 ng/mL	Standard Deviation 1.36
GLWL-01 Part A Placebo	Change From Baseline in C-Peptide Concentration (Part B)	0.457 ng/mL	Standard Deviation 0.8498
GLWL-01 Part B Placebo	Change From Baseline in C-Peptide Concentration (Part B)	0.043 ng/mL	Standard Deviation 0.6513

Secondary

Change From Baseline in Hip Circumference (Part B)

Time frame: Baseline to Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Change From Baseline in Hip Circumference (Part B)	-1.05 centimeters	Standard Deviation 2.94
GLWL-01 Part A (50 mg)	Change From Baseline in Hip Circumference (Part B)	0.960 centimeters	Standard Deviation 7.442
GLWL-01 Part A (150 mg)	Change From Baseline in Hip Circumference (Part B)	1.283 centimeters	Standard Deviation 2.337
GLWL-01 Part A (300 mg)	Change From Baseline in Hip Circumference (Part B)	-0.417 centimeters	Standard Deviation 2.094
GLWL-01 Part A (600 mg)	Change From Baseline in Hip Circumference (Part B)	0.167 centimeters	Standard Deviation 0.753
GLWL-01 Part A Placebo	Change From Baseline in Hip Circumference (Part B)	-0.333 centimeters	Standard Deviation 0.516
GLWL-01 Part B Placebo	Change From Baseline in Hip Circumference (Part B)	0.192 centimeters	Standard Deviation 6.86

Secondary

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.

Time frame: Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Change From Baseline in Insulin Concentration (Part B)	-3.60 uU/mL	Standard Deviation 7.579
GLWL-01 Part A (50 mg)	Change From Baseline in Insulin Concentration (Part B)	-3.89 uU/mL	Standard Deviation 11.533
GLWL-01 Part A (150 mg)	Change From Baseline in Insulin Concentration (Part B)	-9.75 uU/mL	Standard Deviation 10.687
GLWL-01 Part A (300 mg)	Change From Baseline in Insulin Concentration (Part B)	2.12 uU/mL	Standard Deviation 5.878
GLWL-01 Part A (600 mg)	Change From Baseline in Insulin Concentration (Part B)	1.27 uU/mL	Standard Deviation 9.194
GLWL-01 Part A Placebo	Change From Baseline in Insulin Concentration (Part B)	0.23 uU/mL	Standard Deviation 7.653
GLWL-01 Part B Placebo	Change From Baseline in Insulin Concentration (Part B)	2.39 uU/mL	Standard Deviation 8.263

Secondary

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.

Time frame: Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Change From Baseline in Postprandial Glucose (Part B)	18.8 mg/dL	Standard Deviation 11.7
GLWL-01 Part A (50 mg)	Change From Baseline in Postprandial Glucose (Part B)	11.6 mg/dL	Standard Deviation 27.74
GLWL-01 Part A (150 mg)	Change From Baseline in Postprandial Glucose (Part B)	-13.7 mg/dL	Standard Deviation 33.16
GLWL-01 Part A (300 mg)	Change From Baseline in Postprandial Glucose (Part B)	10.7 mg/dL	Standard Deviation 27.4
GLWL-01 Part A (600 mg)	Change From Baseline in Postprandial Glucose (Part B)	29.3 mg/dL	Standard Deviation 49.43
GLWL-01 Part A Placebo	Change From Baseline in Postprandial Glucose (Part B)	29.7 mg/dL	Standard Deviation 25.77
GLWL-01 Part B Placebo	Change From Baseline in Postprandial Glucose (Part B)	13.2 mg/dL	Standard Deviation 41.41

Secondary

Change From Baseline in Waist Circumference (Part B)

Time frame: Baseline to Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Change From Baseline in Waist Circumference (Part B)	-1.275 centimeters	Standard Deviation 3.522
GLWL-01 Part A (50 mg)	Change From Baseline in Waist Circumference (Part B)	1.360 centimeters	Standard Deviation 5.755
GLWL-01 Part A (150 mg)	Change From Baseline in Waist Circumference (Part B)	-3.517 centimeters	Standard Deviation 4.001
GLWL-01 Part A (300 mg)	Change From Baseline in Waist Circumference (Part B)	-1.383 centimeters	Standard Deviation 5.123
GLWL-01 Part A (600 mg)	Change From Baseline in Waist Circumference (Part B)	-1.250 centimeters	Standard Deviation 1.091
GLWL-01 Part A Placebo	Change From Baseline in Waist Circumference (Part B)	-0.083 centimeters	Standard Deviation 0.492
GLWL-01 Part B Placebo	Change From Baseline in Waist Circumference (Part B)	-0.867 centimeters	Standard Deviation 4.026

Secondary

Change From Baseline in Weight (Part B)

Time frame: Baseline to Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Change From Baseline in Weight (Part B)	-0.375 kilograms (kg)	Standard Deviation 0.763
GLWL-01 Part A (50 mg)	Change From Baseline in Weight (Part B)	-0.340 kilograms (kg)	Standard Deviation 0.786
GLWL-01 Part A (150 mg)	Change From Baseline in Weight (Part B)	-0.150 kilograms (kg)	Standard Deviation 0.995
GLWL-01 Part A (300 mg)	Change From Baseline in Weight (Part B)	-0.417 kilograms (kg)	Standard Deviation 0.741
GLWL-01 Part A (600 mg)	Change From Baseline in Weight (Part B)	0.417 kilograms (kg)	Standard Deviation 1.229
GLWL-01 Part A Placebo	Change From Baseline in Weight (Part B)	0.350 kilograms (kg)	Standard Deviation 0.356
GLWL-01 Part B Placebo	Change From Baseline in Weight (Part B)	-0.025 kilograms (kg)	Standard Deviation 0.717

Secondary

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

Time frame: Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Elimination Half-Life (T1/2) (Part A)	3.32 hours	Geometric Coefficient of Variation 8.8
GLWL-01 Part A (50 mg)	Elimination Half-Life (T1/2) (Part A)	3.77 hours	Geometric Coefficient of Variation 23.9
GLWL-01 Part A (150 mg)	Elimination Half-Life (T1/2) (Part A)	5.22 hours	Geometric Coefficient of Variation 25.3
GLWL-01 Part A (300 mg)	Elimination Half-Life (T1/2) (Part A)	5.25 hours	Geometric Coefficient of Variation 25.8
GLWL-01 Part A (600 mg)	Elimination Half-Life (T1/2) (Part A)	5.47 hours	Geometric Coefficient of Variation 19

Secondary

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

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Elimination Half-Life (T1/2) (Part B)	5.33 hours	Geometric Coefficient of Variation 12.1
GLWL-01 Part A (50 mg)	Elimination Half-Life (T1/2) (Part B)	6.16 hours	Geometric Coefficient of Variation 15.16
GLWL-01 Part A (150 mg)	Elimination Half-Life (T1/2) (Part B)	5.24 hours	Geometric Coefficient of Variation 20.3
GLWL-01 Part A (300 mg)	Elimination Half-Life (T1/2) (Part B)	5.94 hours	Geometric Coefficient of Variation 14.9
GLWL-01 Part A (600 mg)	Elimination Half-Life (T1/2) (Part B)	5.12 hours	Geometric Coefficient of Variation 18.5
GLWL-01 Part A Placebo	Elimination Half-Life (T1/2) (Part B)	6.26 hours	Geometric Coefficient of Variation 16.7

Secondary

Fasting Glucose Concentration (Part B)

Fasting glucose concentration after 28 day treatment

Time frame: Baseline to Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Fasting Glucose Concentration (Part B)	1.15 mmol/L	Standard Deviation 1.139
GLWL-01 Part A (50 mg)	Fasting Glucose Concentration (Part B)	1.10 mmol/L	Standard Deviation 1.52
GLWL-01 Part A (150 mg)	Fasting Glucose Concentration (Part B)	-0.20 mmol/L	Standard Deviation 2.1
GLWL-01 Part A (300 mg)	Fasting Glucose Concentration (Part B)	0.63 mmol/L	Standard Deviation 0.299
GLWL-01 Part A (600 mg)	Fasting Glucose Concentration (Part B)	-1.13 mmol/L	Standard Deviation 1.381
GLWL-01 Part A Placebo	Fasting Glucose Concentration (Part B)	-0.10 mmol/L	Standard Deviation 2.104
GLWL-01 Part B Placebo	Fasting Glucose Concentration (Part B)	0.91 mmol/L	Standard Deviation 2.116

Secondary

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

Time frame: Pre-Dose and 24-hours Post-Dose

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Fraction of Drug Excreted in the Urine (Fe) (Part A)	18.7 percentage of the drug	Standard Deviation 6.11
GLWL-01 Part A (50 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part A)	23.3 percentage of the drug	Standard Deviation 5.13
GLWL-01 Part A (150 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part A)	24.6 percentage of the drug	Standard Deviation 8.08
GLWL-01 Part A (300 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part A)	33.6 percentage of the drug	Standard Deviation 5.07
GLWL-01 Part A (600 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part A)	31.8 percentage of the drug	Standard Deviation 6.23

Secondary

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

Time frame: Pre-Dose and 24-hours Post-Dose on Day 28

Arm	Measure	Value (MEAN)	Dispersion
GLWL-01 Part A (10mg)	Fraction of Drug Excreted in the Urine (Fe) (Part B)	56.3 percentage of the drug	Standard Deviation 25.74
GLWL-01 Part A (50 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part B)	63.2 percentage of the drug	Standard Deviation 6.562
GLWL-01 Part A (150 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part B)	41.5 percentage of the drug	Standard Deviation 11.15
GLWL-01 Part A (300 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part B)	38.9 percentage of the drug	Standard Deviation 5.761
GLWL-01 Part A (600 mg)	Fraction of Drug Excreted in the Urine (Fe) (Part B)	60.5 percentage of the drug	Standard Deviation 14.91
GLWL-01 Part A Placebo	Fraction of Drug Excreted in the Urine (Fe) (Part B)	48.9 percentage of the drug	Standard Deviation 12.89

Secondary

Maximum Observed Drug Concentration (Cmax) (Part A)

Time frame: Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Maximum Observed Drug Concentration (Cmax) (Part A)	0.121 µg/mL	Geometric Coefficient of Variation 8.4
GLWL-01 Part A (50 mg)	Maximum Observed Drug Concentration (Cmax) (Part A)	0.600 µg/mL	Geometric Coefficient of Variation 35.4
GLWL-01 Part A (150 mg)	Maximum Observed Drug Concentration (Cmax) (Part A)	2.47 µg/mL	Geometric Coefficient of Variation 39.9
GLWL-01 Part A (300 mg)	Maximum Observed Drug Concentration (Cmax) (Part A)	5.08 µg/mL	Geometric Coefficient of Variation 17.6
GLWL-01 Part A (600 mg)	Maximum Observed Drug Concentration (Cmax) (Part A)	11.5 µg/mL	Geometric Coefficient of Variation 23.9

Secondary

Maximum Observed Drug Concentration (Cmax) (Part B)

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GLWL-01 Part A (10mg)	Maximum Observed Drug Concentration (Cmax) (Part B)	785 ng/mL	Geometric Coefficient of Variation 45.8
GLWL-01 Part A (50 mg)	Maximum Observed Drug Concentration (Cmax) (Part B)	37.90 ng/mL	Geometric Coefficient of Variation 28.1
GLWL-01 Part A (150 mg)	Maximum Observed Drug Concentration (Cmax) (Part B)	62.80 ng/mL	Geometric Coefficient of Variation 10.6
GLWL-01 Part A (300 mg)	Maximum Observed Drug Concentration (Cmax) (Part B)	10800 ng/mL	Geometric Coefficient of Variation 31.5
GLWL-01 Part A (600 mg)	Maximum Observed Drug Concentration (Cmax) (Part B)	16300 ng/mL	Geometric Coefficient of Variation 25.9
GLWL-01 Part A Placebo	Maximum Observed Drug Concentration (Cmax) (Part B)	18200 ng/mL	Geometric Coefficient of Variation 33.7

Secondary

Time to Observed Cmax (Tmax) (Part A)

Time frame: Pre-dose, 0.5, 1, 2, 4.5, 6, 8.5, 12.5, 24, 28.5, 48, 96 and 144 hours post-dose

Arm	Measure	Value (MEDIAN)
GLWL-01 Part A (10mg)	Time to Observed Cmax (Tmax) (Part A)	1.00 hours
GLWL-01 Part A (50 mg)	Time to Observed Cmax (Tmax) (Part A)	1.51 hours
GLWL-01 Part A (150 mg)	Time to Observed Cmax (Tmax) (Part A)	1.02 hours
GLWL-01 Part A (300 mg)	Time to Observed Cmax (Tmax) (Part A)	1.50 hours
GLWL-01 Part A (600 mg)	Time to Observed Cmax (Tmax) (Part A)	1.00 hours

Secondary

Time to Observed Cmax (Tmax) (Part B)

Time frame: Predose, 0.5, 1, 2, 4.5, 6, 8.5, 12, 13, 14, 16, 24, 48, 168, and 336 hours post dose starting on Day 28

Arm	Measure	Value (MEDIAN)
GLWL-01 Part A (10mg)	Time to Observed Cmax (Tmax) (Part B)	2.00 hours
GLWL-01 Part A (50 mg)	Time to Observed Cmax (Tmax) (Part B)	2.00 hours
GLWL-01 Part A (150 mg)	Time to Observed Cmax (Tmax) (Part B)	1.00 hours
GLWL-01 Part A (300 mg)	Time to Observed Cmax (Tmax) (Part B)	3.25 hours
GLWL-01 Part A (600 mg)	Time to Observed Cmax (Tmax) (Part B)	2.00 hours
GLWL-01 Part A Placebo	Time to Observed Cmax (Tmax) (Part B)	4.5 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GLWL-01

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Change From Baseline in Hip Circumference (Part B)

Change From Baseline in Insulin Concentration (Part B)

Change From Baseline in Postprandial Glucose (Part B)

Change From Baseline in Waist Circumference (Part B)

Change From Baseline in Weight (Part B)

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

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

Fasting Glucose Concentration (Part B)

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

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

Maximum Observed Drug Concentration (Cmax) (Part A)

Maximum Observed Drug Concentration (Cmax) (Part B)

Time to Observed Cmax (Tmax) (Part A)

Time to Observed Cmax (Tmax) (Part B)