Study of GS-4571 in Healthy Participants, Nondiabetic Obese Participants, and Nonobese Participants With Type 2 Diabetes Mellitus (T2DM)
- Registration Number
- NCT06562907
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The goal of this clinical study is to learn more about the study drug, GS-4571, and how safe it is in 3 groups, i) Healthy participants, ii) Healthy non-diabetic obese participants, and iii) Non-obese participants with Type 2 Diabetes Mellitus (T2DM).
The primary objectives of this study are:
* To characterize the pharmacokinetics (PK) of GS-4571 following single and multiple ascending oral doses of GS-4571.
* To evaluate the effect of concomitant food intake and (if conducted) a representative acid-reducing agent (proton pump inhibitor (PPI), omeprazole) on the PK of GS-4571.
* To evaluate the safety and tolerability of single and multiple ascending oral doses of GS-4571.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 134
Inclusion Criteria
- Individuals must be glucagon-like peptide-1 receptor agonist (GLP-1RA) naïve OR last dose was at least 6 months prior to screening.
- Part A (SAD) and Part B (Food/PPI Effect): eligible individuals in Cohorts 1-4, (optional cohort 5) and 6 will include healthy individuals with BMI of ≥ 19 and < 30 kg/m^2, and no significant medical history.
Individuals will also be in good general health as determined by the investigator at the screening evaluation performed no more than 28 days prior to the scheduled first dose.
- Part C (MAD in nondiabetic obese individuals): Eligible individuals in Cohorts 7-9 and (optional cohort 10) will be individuals with obesity with BMI ≥ 30 kg/m^2 and < 45 kg/m^2 with a total body weight > 50 kg, and nondiabetic (HbA1c < 6.5%). Eligible individuals will also be individuals with stable body weight (< 5% change) for 90 days prior to screening visit based on individual report.
- Part D (multiple doses in non-obese T2DM): eligible individuals in Cohort 11 will be individuals with T2DM HbA1c ≥ 7.0% and ≤ 10.5% with BMI of ≥ 19 and < 30 kg/m^2 and treated with diet and/or exercise, and/or metformin monotherapy.
Key
Exclusion Criteria
- Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with individual treatment, assessment, or compliance with the protocol. This would include acute pancreatitis, or history of pancreatitis, acute gallbladder disease, and renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes [with the exception of T2DM for individuals included in Part D only]), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment.
- Current symptoms of diabetic retinopathy or examination indicating diabetic retinopathy within one year of screening.
- Any electrolyte disturbances identified at screening considered to be clinically significant in the opinion of the investigator (eg, hypokalemia, hypocalcemia, or hypomagnesemia).
- Any condition that could lead to electrolyte disturbances (eg, eating disorder) in the opinion of the investigator.
- History of syncope, palpitations, or unexplained dizziness.
- Active, or history of, significant cardiac disease or conduction abnormality
- History of implanted defibrillator or pacemaker.
- Have been treated with the following within 6 months prior to screening or is expected to receive these agents during the study: GLP-1RAs, systemic steroids, immunosuppressant therapies, or chemotherapeutic agents (eg, corticosteroids, immunoglobulins, other immune or cytokine-based therapies).
- Previously stopped use of GLP-1RAs secondary to severe side effects including nausea, constipation, diarrhea, or emesis.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A Single-ascending Dose (SAD) in Healthy Participants GS-4571 Participants will be randomized into 4 + (optional) 1 dose escalating cohorts and will receive GS-4571 or placebo to match (PTM) GS-4571 on Day 1, to determine the maximum tolerated dose: * Cohort 1: Dose 1 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 2: Dose 2 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 3: Dose 3 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 4: Dose 4 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 5 (optional): Dose 5 GS-4571, administered orally as a single dose, in a fasting state. Part A Single-ascending Dose (SAD) in Healthy Participants Placebo Participants will be randomized into 4 + (optional) 1 dose escalating cohorts and will receive GS-4571 or placebo to match (PTM) GS-4571 on Day 1, to determine the maximum tolerated dose: * Cohort 1: Dose 1 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 2: Dose 2 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 3: Dose 3 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 4: Dose 4 GS-4571, administered orally as a single dose, in a fasting state. * Cohort 5 (optional): Dose 5 GS-4571, administered orally as a single dose, in a fasting state. Part B Food/PPI Effect in Healthy Participants GS-4571 Participants will be randomized into 2 sequence groups in Cohort 6 and will receive the highest dose found to be safe and well tolerated in Part A of GS-4571 and omeprazole. The two sequential groups will receive the following treatments: * Treatment A: Up to the highest single dose of GS-4571 evaluated in Part A, fasting. * Treatment B: Up to the highest single dose of GS-4571 evaluated in Part A, nonfasting (high-fat/high-calorie meal). * Treatment C (optional): Omeprazole, once-daily (QD) for 5 days, fasting. * Treatment D (optional): Omeprazole followed by up to the highest single dose of GS-4571 evaluated in Part A, 2 hours later, fasting. Part B Food/PPI Effect in Healthy Participants Omeprazole Participants will be randomized into 2 sequence groups in Cohort 6 and will receive the highest dose found to be safe and well tolerated in Part A of GS-4571 and omeprazole. The two sequential groups will receive the following treatments: * Treatment A: Up to the highest single dose of GS-4571 evaluated in Part A, fasting. * Treatment B: Up to the highest single dose of GS-4571 evaluated in Part A, nonfasting (high-fat/high-calorie meal). * Treatment C (optional): Omeprazole, once-daily (QD) for 5 days, fasting. * Treatment D (optional): Omeprazole followed by up to the highest single dose of GS-4571 evaluated in Part A, 2 hours later, fasting. Part C Multiple-ascending Dose (MAD) in Nondiabetic Obese Participants GS-4571 Participants randomized in Cohorts 7-9 will be randomized to receive up to 4 escalating doses of GS-4571 or PTM QD for 12 weeks, as follows: * Cohort 7: Up to dose determined from Part A of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 8: Up to 3-fold the Cohort 7 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 9: Up to 2-fold the Cohort 8 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 10 is optional and will receive GS-4571 or PTM QD for 12 weeks in case it is opened for enrollment as follows: * Up to 2-fold the Cohort 9 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state. Part C Multiple-ascending Dose (MAD) in Nondiabetic Obese Participants Placebo Participants randomized in Cohorts 7-9 will be randomized to receive up to 4 escalating doses of GS-4571 or PTM QD for 12 weeks, as follows: * Cohort 7: Up to dose determined from Part A of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 8: Up to 3-fold the Cohort 7 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 9: Up to 2-fold the Cohort 8 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state * Cohort 10 is optional and will receive GS-4571 or PTM QD for 12 weeks in case it is opened for enrollment as follows: * Up to 2-fold the Cohort 9 dose of GS-4571 or PTM in obese participants, QD, in a non-fasting state. Part D Multiple Dose in Nonobese Participants With T2DM GS-4571 Participants randomized in Cohort 11 will receive up to the highest dose of GS-4571 or PTM in T2DM, QD, in a non-fasting state for 12 weeks. Part D Multiple Dose in Nonobese Participants With T2DM Placebo Participants randomized in Cohort 11 will receive up to the highest dose of GS-4571 or PTM in T2DM, QD, in a non-fasting state for 12 weeks.
- Primary Outcome Measures
Name Time Method Single-Dose PK Parameter AUCinf of GS-4571 Up to 96 hours postdose AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time.
Single-Dose PK Parameter Cmax of GS-4571 Up to 96 hours postdose Cmax is defined as the maximum observed concentration of drug in plasma.
Multiple-Dose Plasma PK Parameter: AUCtau of GS-4571 Up to 96 hours postdose AUCtau is defined as area under the concentration versus time curve over the dosing interval.
Multiple-Dose Plasma PK Parameter: Cmax of GS-4571 Up to 96 hours postdose Cmax is defined as the maximum observed concentration of drug in plasma.
Percentage of Participants of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Deaths Day 1 up to 95 days Percentage of Participants of Treatment-Emergent Laboratory Abnormalities Day 1 up to 95 days
- Secondary Outcome Measures
Name Time Method Percentage Change From Baseline (CFB) in Body Weight in Nondiabetic Obese Participants Day 1 up to 95 days
Trial Locations
- Locations (2)
ICON
🇺🇸Salt Lake City, Utah, United States
ICON Early Phase Services, LLC
🇺🇸San Antonio, Texas, United States