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

• ClinicalTrials.gov Identifier: NCT02876796
• Recruitment Status: Completed
• First Posted: August 24, 2016
• Last Update Posted: August 24, 2016
• Sponsor: Gilead Sciences
• Collaborator: Nimbus Apollo
• Information provided by (Responsible Party): Gilead Sciences

Study Description

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.

Condition or disease	Intervention/treatment	Phase
PD Effects of GS-0976 (NDI-010976) on Fractional DNL	Drug: GS-0976; Drug: Placebo; Other: 1-13C acetate; Other: Fructose solution	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study To Evaluate the Pharmacodynamic Effects of A Single Oral Dose of NDI-010976 in Healthy Adult Subjects
• Study Start Date: August 2015
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: GS-0976; Capsule(s) administered orally; Other Name: NDI-010976; Drug: Placebo; Capsule(s) administered orally; Other: 1-13C acetate; 10 g ± 0.25 g in 1000 mL 0.45% saline solution administered intravenously for 19 hours; Other: Fructose solution; Fructose solution administered orally under fasted conditions immediately after study drug and every 30 minutes for a total of 20 doses
Experimental: 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	Drug: GS-0976; Capsule(s) administered orally; Other Name: NDI-010976; Drug: Placebo; Capsule(s) administered orally; Other: 1-13C acetate; 10 g ± 0.25 g in 1000 mL 0.45% saline solution administered intravenously for 19 hours; Other: Fructose solution; Fructose solution administered orally under fasted conditions immediately after study drug and every 30 minutes for a total of 20 doses
Experimental: 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	Drug: GS-0976; Capsule(s) administered orally; Other Name: NDI-010976; Drug: Placebo; Capsule(s) administered orally; Other: 1-13C acetate; 10 g ± 0.25 g in 1000 mL 0.45% saline solution administered intravenously for 19 hours; Other: Fructose solution; Fructose solution administered orally under fasted conditions immediately after study drug and every 30 minutes for a total of 20 doses

Outcome Measures

Primary Outcome Measures :

1. Change in fractional DNL (% new palmitate) [ Time Frame: Predose and up to 10 hours postdose ]
2. Change in DNL over time following administration of GS-0976 and placebo [ Time Frame: Predose and up to 10 hours postdose ]
3. Change from baseline over time in adiponectin [ Time Frame: Baseline and up to 10 hours postdose ]
4. Percent change from baseline over time in adiponectin [ Time Frame: Baseline and up to 10 hours postdose ]
5. Change from baseline over time in leptin [ Time Frame: Baseline and up to 10 hours postdose ]
6. Percent change from baseline over time in leptin [ Time Frame: Baseline and up to 10 hours postdose ]
7. Change from baseline over time in blood ketones [ Time Frame: Baseline and up to 10 hours postdose ]
8. Percent change from baseline over time in blood ketones [ Time Frame: Baseline and up to 10 hours postdose ]
9. Change from baseline over time in lipid profile [ Time Frame: Baseline and up to 10 hours postdose ]
10. Percent change from baseline over time in lipid profile [ Time Frame: Baseline and up to 10 hours postdose ]

Secondary Outcome Measures :

1. Number and severity of treatment-emergent adverse events (TEAEs) following single oral doses of GS-0976 and placebo [ Time Frame: Up to 42 days ]
2. Percentage of participants experiencing abnormal clinical laboratory tests [ Time Frame: Up to 42 days ]
3. Pharmacokinetics (PK) of GS-0976 and its metabolite: tmax [ Time Frame: Baseline and up to 10 hours postdose ]
   Tmax is defined as the time (observed time point) of Cmax.
4. PK of GS-0976 and its metabolite: Cmax [ Time Frame: Baseline and up to 10 hours postdose ]
   Cmax is defined as the maximum concentration of drug.
5. PK of GS-0976 and its metabolite: AUC_0-t [ Time Frame: 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".

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Arizona

Phoenix, Arizona, United States

Sponsors and Collaborators

Gilead Sciences

Nimbus Apollo

Investigators

• Study Director: Rob Myers, MD; Gilead Sciences

More Information

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02876796
• Other Study ID Numbers: 0976-103
• First Posted: August 24, 2016
• Last Update Posted: August 24, 2016
• Last Verified: August 2016

Keywords provided by Gilead Sciences:

fractional de novo lipogenesis; DNL; pharmacodynamic; pharmacokinetic

Additional relevant MeSH terms:

Firsocostat; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action