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

Tracking Information

• First Submitted Date: August 19, 2016
• First Posted Date: August 24, 2016
• Last Update Posted Date: August 24, 2016
• Study Start Date: August 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 19, 2016)

• 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 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 ]
• Percent change from baseline over time in lipid profile [ Time Frame: Baseline and up to 10 hours postdose ]

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 19, 2016)

• Number and severity of treatment-emergent adverse events (TEAEs) following single oral doses of GS-0976 and placebo [ Time Frame: Up to 42 days ]
• Percentage of participants experiencing abnormal clinical laboratory tests [ Time Frame: Up to 42 days ]
• 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.
• 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.
• 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".

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Pharmacodynamic Effects of a Single Oral Dose of GS-0976 (NDI-010976) in Healthy Adult Subjects
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator)
• Condition: PD Effects of GS-0976 (NDI-010976) on Fractional DNL

Intervention

• 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

Study Arms

• 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

  Interventions:

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

  Interventions:

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

  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 19, 2016): 30
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02876796
• Other Study ID Numbers: 0976-103
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Nimbus Apollo

Investigators

• Study Director: Rob Myers, MD; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: August 2016