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

NCT ID: NCT02377362

Last Updated: 2019-03-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-11-09

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).

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GLWL-01, Part A

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

Group Type: EXPERIMENTAL

GLWL-01, Part A

Intervention Type: DRUG

Capsules administered orally, in 2 out of 3 periods

Placebo, Part A

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

Group Type: PLACEBO_COMPARATOR

Placebo, Part A

Intervention Type: DRUG

Capsules administered orally in 1 out of 3 periods

GLWL-01, Part B

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

Group Type: EXPERIMENTAL

GLWL-01, Part B

Intervention Type: DRUG

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

Placebo, Part B

Multiple daily doses of placebo to match GLWL-01

Group Type: PLACEBO_COMPARATOR

Placebo, Part B

Intervention Type: DRUG

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

GLWL-01, Part C

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

Group Type: EXPERIMENTAL

GLWL-01, Part C

Intervention Type: DRUG

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

Placebo, Part C

Multiple daily doses of placebo to match GLWL-01

Group Type: PLACEBO_COMPARATOR

Placebo, Part C

Intervention Type: DRUG

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

Interventions

GLWL-01, Part A

Capsules administered orally, in 2 out of 3 periods

Intervention Type: DRUG

Placebo, Part A

Capsules administered orally in 1 out of 3 periods

Intervention Type: DRUG

GLWL-01, Part B

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

Intervention Type: DRUG

Placebo, Part B

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

Intervention Type: DRUG

GLWL-01, Part C

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

Intervention Type: DRUG

Placebo, Part C

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

Intervention Type: DRUG

Eligibility 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:

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GLWL Research Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Email choruspharma@lists.lilly.com

Role: STUDY_DIRECTOR

GLWL Research Inc.

Locations

Celerion

Tempe, Arizona, United States

Profil Institute for Clinical Research, Inc.

Chula Vista, California, United States

Clinical Pharmacology of Miami, Inc.

Miami, Florida, United States

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States

Countries

United States

Other Identifiers

GLWL-SMP

Identifier Type: -

Identifier Source: org_study_id