Clinical trial NCT06562907: Study of GS-4571 in Healthy Participants, Nondiabetic Obese Participants, and Nonobese Participants With Type 2 Diabetes Mellitus (T2DM)
Official title: A Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Single Ascending Oral Doses of GS-4571 in Healthy Participants, Multiple Ascending Oral Doses of GS-4571 in Nondiabetic Obese Participants and Nonobese Participants With Type 2 Diabetes Mellitus (T2DM), and to Evaluate the Effect of Food and an Acid-Reducing Agent on Pharmacokinetics of GS-4571
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Weight Management
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2024-08-20
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Primary outcomes:
measure: Single-Dose PK Parameter AUCinf of GS-4571
timeFrame: Up to 96 hours postdose
measure: Single-Dose PK Parameter Cmax of GS-4571
timeFrame: Up to 96 hours postdose
measure: Multiple-Dose Plasma PK Parameter: AUCtau of GS-4571
timeFrame: Up to 96 hours postdose
measure: Multiple-Dose Plasma PK Parameter: Cmax of GS-4571
timeFrame: Up to 96 hours postdose
measure: Percentage of Participants of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Deaths
timeFrame: Day 1 up to 95 days
measure: Percentage of Participants of Treatment-Emergent Laboratory Abnormalities
timeFrame: Day 1 up to 95 days
Secondary outcomes:
measure: Percentage Change From Baseline (CFB) in Body Weight in Nondiabetic Obese Participants
timeFrame: Day 1 up to 95 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: ICON Early Phase Services, LLC
state: Texas
city: Salt Lake City
country: United States
facility: ICON
state: Utah
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: