Study of GS-4571 in Healthy Participants, Nondiabetic Obese Participants, and Nonobese Participants With Type 2 Diabetes Mellitus (T2DM)

NCT06562907 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GS-US-506-6610
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 3

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.

Conditions

Weight Management

Outcome Measures

Primary Outcomes (6)

• Single-Dose PK Parameter AUCinf of GS-4571

  AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time.

  Up to 96 hours postdose

• Single-Dose PK Parameter Cmax of GS-4571

  Cmax is defined as the maximum observed concentration of drug in plasma.

  Up to 96 hours postdose

• Multiple-Dose Plasma PK Parameter: AUCtau of GS-4571

  AUCtau is defined as area under the concentration versus time curve over the dosing interval.

  Up to 96 hours postdose

• Multiple-Dose Plasma PK Parameter: Cmax of GS-4571

  Cmax is defined as the maximum observed concentration of drug in plasma.

  Up to 96 hours postdose

• 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 Outcomes (1)

• Percentage Change From Baseline (CFB) in Body Weight in Nondiabetic Obese Participants

  Day 1 up to 95 days

Study Arms (4)

Part A Single-ascending Dose (SAD) in Healthy Participants

EXPERIMENTAL

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.

Drug: GS-4571; Drug: Placebo

Part B Food/PPI Effect in Healthy Participants

EXPERIMENTAL

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.

Drug: GS-4571; Drug: Omeprazole

Part C Multiple-ascending Dose (MAD) in Nondiabetic Obese Participants

EXPERIMENTAL

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.

Drug: GS-4571; Drug: Placebo

Part D Multiple Dose in Nonobese Participants With T2DM

EXPERIMENTAL

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.

Drug: GS-4571; Drug: Placebo

Interventions

GS-4571 DRUG

Administered orally

Part A Single-ascending Dose (SAD) in Healthy Participants; Part B Food/PPI Effect in Healthy Participants; Part C Multiple-ascending Dose (MAD) in Nondiabetic Obese Participants; Part D Multiple Dose in Nonobese Participants With T2DM

Placebo DRUG

Administered orally

Part A Single-ascending Dose (SAD) in Healthy Participants; Part C Multiple-ascending Dose (MAD) in Nondiabetic Obese Participants; Part D Multiple Dose in Nonobese Participants With T2DM

Omeprazole DRUG

Administered orally

Part B Food/PPI Effect in Healthy Participants

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (3)

Qps-Mra, Llc.

Miami, Florida, 33143, United States

RECRUITING

ICON Early Phase Services, LLC

San Antonio, Texas, 78209, United States

RECRUITING

ICON

Salt Lake City, Utah, 84124, United States

RECRUITING

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

Study Design

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

Study Record Dates

• First Submitted: August 16, 2024
• First Posted: August 20, 2024
• Study Start: August 28, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)