Study to Evaluate the Pharmacodynamic Effects of a Single Oral Dose of GS-0976 (NDI-010976) in Healthy Adult Subjects
Phase 1
Completed
- Conditions
- PD Effects of GS-0976 (NDI-010976) on Fractional DNL
- Interventions
- Registration Number
- NCT02876796
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to assess the pharmacodynamic (PD) effects of GS-0976 (NDI-010976) on fractional de novo lipogenesis (DNL) following a single oral dose administration in overweight and/or obese, but otherwise healthy, male adults.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 30
Inclusion Criteria
- Overweight and/or obese, but otherwise healthy males
- Weight ≥ 50.0 kg
- Body Mass Index (BMI): 25.0 - 32.0 kg/m^2, inclusive
Exclusion Criteria
- Intolerance to or malabsorption of fructose
- A history of clinically significant gastrointestinal disease and/or surgery, which would result in the subject's inability to absorb or metabolize the study drug (e.g., gastrectomy, gastric bypass, cholecystectomy).
- In the opinion of the Investigator, a history of clinically significant hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, metabolic , endocrine disorder (e.g., diabetes, thyroid disease), or cardiovascular disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 50 mg GS-0976 (Cohort 1) GS-0976 Sequence 1: Period 1 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 2: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution 200 mg GS-0976 (Cohort 2) GS-0976 Sequence 3: Period 1 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 4: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution 50 mg GS-0976 (Cohort 1) Fructose solution Sequence 1: Period 1 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 2: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution 50 mg GS-0976 (Cohort 1) 1-13C acetate Sequence 1: Period 1 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 2: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution 200 mg GS-0976 (Cohort 2) Placebo Sequence 3: Period 1 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 4: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution 20 mg GS-0976 (Cohort 3) GS-0976 Sequence 5: Period 1 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 6: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution 20 mg GS-0976 (Cohort 3) Fructose solution Sequence 5: Period 1 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 6: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution 50 mg GS-0976 (Cohort 1) Placebo Sequence 1: Period 1 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 2: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 50 mg (1 x 50 mg capsule) + IV infusion 1-13C acetate and fructose solution 200 mg GS-0976 (Cohort 2) 1-13C acetate Sequence 3: Period 1 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 4: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution 200 mg GS-0976 (Cohort 2) Fructose solution Sequence 3: Period 1 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 4: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 200 mg (1 x 200 mg capsule) + IV infusion 1-13C acetate and fructose solution 20 mg GS-0976 (Cohort 3) 1-13C acetate Sequence 5: Period 1 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 6: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution 20 mg GS-0976 (Cohort 3) Placebo Sequence 5: Period 1 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): placebo + IV infusion 1-13C acetate and fructose solution Sequence 6: Period 1 (2 days): placebo + IV infusion 1-13C acetate and fructose solution; Washout Period (minimum of 5 days); Period 2 (2 days): 20 mg (2 X 10 mg capsule) + IV infusion 1-13C acetate and fructose solution
- Primary Outcome Measures
Name Time Method Change in fractional DNL (% new palmitate) Predose and up to 10 hours postdose Change in DNL over time following administration of GS-0976 and placebo Predose and up to 10 hours postdose Change from baseline over time in adiponectin Baseline and up to 10 hours postdose Percent change from baseline over time in adiponectin Baseline and up to 10 hours postdose Change from baseline over time in leptin Baseline and up to 10 hours postdose Percent change from baseline over time in lipid profile Baseline and up to 10 hours postdose Percent change from baseline over time in leptin Baseline and up to 10 hours postdose Change from baseline over time in blood ketones Baseline and up to 10 hours postdose Percent change from baseline over time in blood ketones Baseline and up to 10 hours postdose Change from baseline over time in lipid profile Baseline and up to 10 hours postdose
- Secondary Outcome Measures
Name Time Method Number and severity of treatment-emergent adverse events (TEAEs) following single oral doses of GS-0976 and placebo Up to 42 days Percentage of participants experiencing abnormal clinical laboratory tests Up to 42 days Pharmacokinetics (PK) of GS-0976 and its metabolite: tmax Baseline and up to 10 hours postdose Tmax is defined as the time (observed time point) of Cmax.
PK of GS-0976 and its metabolite: Cmax Baseline and up to 10 hours postdose Cmax is defined as the maximum concentration of drug.
PK of GS-0976 and its metabolite: AUC_0-t Baseline and up to 10 hours postdose AUC_0-t is defined as the concentration of drug over time from time zero to time "t".