A Randomized, Double-Blind, Placebo-Controlled Study To Evaluate the Pharmacodynamic Effects of A Single Oral Dose of NDI-010976 in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- GS-0976
- Conditions
- PD Effects of GS-0976 (NDI-010976) on Fractional DNL
- Sponsor
- Gilead Sciences
- Enrollment
- 30
- Primary Endpoint
- Change in fractional DNL (% new palmitate)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
50 mg GS-0976 (Cohort 1)
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
Intervention: GS-0976
50 mg GS-0976 (Cohort 1)
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
Intervention: Placebo
50 mg GS-0976 (Cohort 1)
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
Intervention: 1-13C acetate
50 mg GS-0976 (Cohort 1)
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
Intervention: Fructose solution
200 mg GS-0976 (Cohort 2)
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
Intervention: GS-0976
200 mg GS-0976 (Cohort 2)
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
Intervention: Placebo
200 mg GS-0976 (Cohort 2)
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
Intervention: 1-13C acetate
200 mg GS-0976 (Cohort 2)
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
Intervention: Fructose solution
20 mg GS-0976 (Cohort 3)
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
Intervention: GS-0976
20 mg GS-0976 (Cohort 3)
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
Intervention: Placebo
20 mg GS-0976 (Cohort 3)
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
Intervention: 1-13C acetate
20 mg GS-0976 (Cohort 3)
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
Intervention: Fructose solution
Outcomes
Primary Outcomes
Change in fractional DNL (% new palmitate)
Time Frame: Predose and up to 10 hours postdose
Change in DNL over time following administration of GS-0976 and placebo
Time Frame: Predose and up to 10 hours postdose
Change from baseline over time in adiponectin
Time Frame: Baseline and up to 10 hours postdose
Percent change from baseline over time in adiponectin
Time Frame: Baseline and up to 10 hours postdose
Change from baseline over time in leptin
Time Frame: Baseline and up to 10 hours postdose
Percent change from baseline over time in lipid profile
Time Frame: Baseline and up to 10 hours postdose
Percent change from baseline over time in leptin
Time Frame: Baseline and up to 10 hours postdose
Change from baseline over time in blood ketones
Time Frame: Baseline and up to 10 hours postdose
Percent change from baseline over time in blood ketones
Time Frame: Baseline and up to 10 hours postdose
Change from baseline over time in lipid profile
Time Frame: Baseline and up to 10 hours postdose
Secondary Outcomes
- 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)
- PK of GS-0976 and its metabolite: Cmax(Baseline and up to 10 hours postdose)
- PK of GS-0976 and its metabolite: AUC_0-t(Baseline and up to 10 hours postdose)