Study to Evaluate the Pharmacodynamic Effects of a Single Oral Dose of GS-0976 (NDI-010976) in Healthy Adult Subjects

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: PD Effects of GS-0976 (NDI-010976) on Fractional DNL

Treatments: Drug: GS-0976; Drug: Placebo; Other: 1-13C acetate; Other: Fructose solution

Study type: Interventional

Funder types: Industry

Identifiers

NCT02876796

0976-103

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

30 participants in 3 patient groups

50 mg GS-0976 (Cohort 1)

Experimental group

Description:

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

Treatment:

Drug: Placebo

Other: Fructose solution

Drug: GS-0976

Other: 1-13C acetate

200 mg GS-0976 (Cohort 2)

Experimental group

Description:

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

Treatment:

Drug: Placebo

Other: Fructose solution

Drug: GS-0976

Other: 1-13C acetate

20 mg GS-0976 (Cohort 3)

Experimental group

Description:

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

Treatment:

Drug: Placebo

Other: Fructose solution

Drug: GS-0976

Other: 1-13C acetate