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

NCT02377362 | Terminated Phase 1 Results

• 1 other identifier: GLWL-SMP
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 4

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

Outcome Measures

Primary Outcomes (2)

• 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

  Baseline to 7 weeks

• 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

  Baseline to 6 weeks

Secondary Outcomes (30)

• 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

• 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

• 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

Study Arms (6)

GLWL-01, Part A

EXPERIMENTAL

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

Drug: GLWL-01, Part A

Placebo, Part A

PLACEBO COMPARATOR

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

Drug: Placebo, Part A

GLWL-01, Part B

EXPERIMENTAL

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

Drug: GLWL-01, Part B

Placebo, Part B

PLACEBO COMPARATOR

Multiple daily doses of placebo to match GLWL-01

Drug: Placebo, Part B

GLWL-01, Part C

EXPERIMENTAL

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

Drug: GLWL-01, Part C

Placebo, Part C

PLACEBO COMPARATOR

Multiple daily doses of placebo to match GLWL-01

Drug: Placebo, Part C

Interventions

GLWL-01, Part A DRUG

Capsules administered orally, in 2 out of 3 periods

GLWL-01, Part A

Placebo, Part A DRUG

Capsules administered orally in 1 out of 3 periods

Placebo, Part A

GLWL-01, Part B DRUG

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

GLWL-01, Part B

Placebo, Part B DRUG

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

Placebo, Part B

GLWL-01, Part C DRUG

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

GLWL-01, Part C

Placebo, Part C DRUG

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

Placebo, Part C

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• GLWL Research Inc.: lead

Study Sites (4)

Celerion

Tempe, Arizona, 85283, United States

Location

Profil Institute for Clinical Research, Inc.

Chula Vista, California, 91911, United States

Location

Clinical Pharmacology of Miami, Inc.

Miami, Florida, 33014, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: GLWL Research Inc

choruspharma@lists.lilly.com

Study Officials

• Email choruspharma@lists.lilly.com

  GLWL Research Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2015
• First Posted: March 3, 2015
• Study Start: March 1, 2015
• Primary Completion: November 9, 2016
• Study Completion: November 9, 2016
• Last Updated: March 21, 2019
• Results First Posted: March 21, 2019

Record last verified: 2019-03

Locations

US (4)