NCT02876796

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2015

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2015

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

August 19, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

August 24, 2016

Completed
Last Updated

August 24, 2016

Status Verified

August 1, 2016

Enrollment Period

1 month

First QC Date

August 19, 2016

Last Update Submit

August 19, 2016

Conditions

Keywords

fractional de novo lipogenesisDNLpharmacodynamicpharmacokinetic

Outcome Measures

Primary Outcomes (10)

  • 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 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

  • Percent change from baseline over time in lipid profile

    Baseline and up to 10 hours postdose

Secondary Outcomes (5)

  • 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

Study Arms (3)

50 mg GS-0976 (Cohort 1)

EXPERIMENTAL

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-0976Drug: PlaceboOther: 1-13C acetateOther: Fructose solution

200 mg GS-0976 (Cohort 2)

EXPERIMENTAL

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-0976Drug: PlaceboOther: 1-13C acetateOther: Fructose solution

20 mg GS-0976 (Cohort 3)

EXPERIMENTAL

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-0976Drug: PlaceboOther: 1-13C acetateOther: Fructose solution

Interventions

Capsule(s) administered orally

Also known as: NDI-010976
20 mg GS-0976 (Cohort 3)200 mg GS-0976 (Cohort 2)50 mg GS-0976 (Cohort 1)

Capsule(s) administered orally

20 mg GS-0976 (Cohort 3)200 mg GS-0976 (Cohort 2)50 mg GS-0976 (Cohort 1)

10 g ± 0.25 g in 1000 mL 0.45% saline solution administered intravenously for 19 hours

20 mg GS-0976 (Cohort 3)200 mg GS-0976 (Cohort 2)50 mg GS-0976 (Cohort 1)

Fructose solution administered orally under fasted conditions immediately after study drug and every 30 minutes for a total of 20 doses

20 mg GS-0976 (Cohort 3)200 mg GS-0976 (Cohort 2)50 mg GS-0976 (Cohort 1)

Eligibility Criteria

Age18 Years - 50 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Overweight and/or obese, but otherwise healthy males
  • Weight ≥ 50.0 kg
  • Body Mass Index (BMI): 25.0 - 32.0 kg/m\^2, inclusive

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Unknown Facility

Phoenix, Arizona, United States

Location

MeSH Terms

Interventions

firsocostat

Study Officials

  • Rob Myers, MD

    Gilead Sciences

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 19, 2016

First Posted

August 24, 2016

Study Start

August 1, 2015

Primary Completion

September 1, 2015

Study Completion

October 1, 2015

Last Updated

August 24, 2016

Record last verified: 2016-08

Locations