PD Effects of GS-0976 (NDI-010976) on Fractional DNL
Conditions
Keywords
fractional de novo lipogenesis, DNL, pharmacodynamic, pharmacokinetic
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.
Interventions
DRUGGS-0976
Capsule(s) administered orally
DRUGPlacebo
Capsule(s) administered orally
OTHER1-13C acetate
10 g ± 0.25 g in 1000 mL 0.45% saline solution administered intravenously for 19 hours
OTHERFructose solution
Fructose solution administered orally under fasted conditions immediately after study drug and every 30 minutes for a total of 20 doses
Sponsors
Nimbus Apollo
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change from baseline over time in lipid profile | 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Tmax is defined as the time (observed time point) of Cmax. |
| PK of GS-0976 and its metabolite: Cmax | 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 | 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. |
| Number and severity of treatment-emergent adverse events (TEAEs) following single oral doses of GS-0976 and placebo | Up to 42 days | — |
Countries
United States
Outcome results
None listed