Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as NDI-010976, Firsocostat, FIR
GS-0976 · 4 trials · 3 indications
Treatment-emergent adverse events (TEAEs) were defined as, any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. Participants were assessed for AEs according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Treatment-emergent laboratory abnormalities, defined as values that increase at least one toxicity grade from baseline at any time post-baseline up to and including the date of last dose of study drug plus 30 days, were summarized by treatment group. Graded laboratory abnormalities were defined using the grading scheme in the CTCAE 5.0.
AUClast is defined as the concentration of drug from time zero to the last observable concentration. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
AUCinf is defined as the concentration of drug extrapolated to infinite time. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Cmax is defined as the maximum observed concentration of drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Tmax is defined as the time (observed time point) of Cmax. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Clast is defined as the last observed quantifiable concentration of drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Tlast is defined as the time (observed time point) of Clast. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
CL/F is defined as the apparent oral clearance following administration of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
Vz/F is defined as the apparent volume of distribution of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
t1/2 is defined as the estimate of the terminal elimination half-life of the drug. The PK of fenofibric acid was evaluated in participants with mild hepatic impairment and matched participants with normal hepatic function (Cohort 4).
| Arm | Type | Description |
|---|---|---|
| Semaglutide | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks |
| Semaglutide + Firsocostat 20 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks |
| Semaglutide + Cilofexor 30 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks |
| Semaglutide + Cilofexor 100 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks |
| Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks |
| Firsocostat 5 mg | EXPERIMENTAL | Participants will receive firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg for 12 weeks. |
| Firsocostat 20 mg | EXPERIMENTAL | Participants will receive firsocostat 2 X 10 mg + 2 x placebo matched to firsocostat 5 mg for 12 weeks. |
| Placebo | EXPERIMENTAL | Participants will receive 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg for 12 weeks. |
| Cohort 1 (Mild Hepatic Impairment): Firsocostat 20 mg | EXPERIMENTAL | Participants with mild hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). |
| Cohort 1 (Normal Hepatic Function): Firsocostat 20 mg | EXPERIMENTAL | Matched normal hepatic function participants to mild hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). |
| Cohort 2 (Moderate Hepatic Impairment): Firsocostat 20 mg | EXPERIMENTAL | Participants with moderate hepatic impairment will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). |
| Cohort 2 (Normal Hepatic Function): Firsocostat 20 mg | EXPERIMENTAL | Matched normal hepatic function participants to moderate hepatic impairment participants will receive a single dose of firsocostat 20 mg (2 × 10 mg capsules). |
| Cohort 3 (Severe Hepatic Impairment): Firsocostat 5 mg | EXPERIMENTAL | Participants with severe hepatic impairment will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule). |
| Cohort 3 (Normal Hepatic Function) Firsocostat 5 mg | EXPERIMENTAL | Matched normal hepatic function participants to severe hepatic impairment participants will receive a single dose of firsocostat 5 mg (1 × 5 mg capsule). |
| Cohort 4 (Mild Hepatic Impairment): Fenofibrate 48 mg | EXPERIMENTAL | Participants with mild hepatic impairment will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet). |
| Cohort 4 (Normal Hepatic Function) Fenofibrate 48 mg | EXPERIMENTAL | Matched normal hepatic function participants to mild hepatic impairment participants, will receive a single dose of fenofibrate 48 mg (1 × 48 mg tablet). |
| 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 |
| 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 |
| 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 |
| Name | Type | Description |
|---|---|---|
| Semaglutide | DRUG | Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly |
| Firsocostat | DRUG | Tablets administered orally once daily |
| Cilofexor | DRUG | Tablets administered orally once daily |
| Placebo | DRUG | Placebo matched to firsocostat orally once daily. |
| Fenofibrate | DRUG | Tablet administered orally on Day 1 |
| GS-0976 | DRUG | Capsule(s) administered orally |
| 1-13C acetate | OTHER | 10 g ± 0.25 g in 1000 mL 0.45% saline solution administered intravenously for 19 hours |
| Fructose solution | OTHER | Fructose solution administered orally under fasted conditions immediately after study drug and every 30 minutes for a total of 20 doses |
Key Inclusion Criteria: * Historical liver biopsy consistent with NASH with stage 2-3 fibrosis according to NASH Clinical Research Network (CRN) classification OR clinical diagnosis of nonalcoholic fatty liver disease and screening FibroTest, magnetic resonance imaging - proton density fat fraction...
GS-0976 is an investigational small molecule developed by Gilead Sciences, Inc. (ticker GILD). It has been studied in a Phase 1 clinical trial evaluating its pharmacodynamic effects in healthy adult subjects. The compound is also known as NDI-010976.
GS-0976 is being developed by Gilead Sciences, Inc., which trades under the ticker GILD. The company sponsored the Phase 1 study of the compound. The drug candidate is also referred to as NDI-010976.
GS-0976 is in Phase 1 clinical development. One Phase 1 trial has been completed, and no active trials are currently listed. The compound has not been approved by the FDA and remains investigational.
GS-0976 has been studied in one completed Phase 1 trial, NCT02876796, titled a study to evaluate the pharmacodynamic effects of a single oral dose of GS-0976 (NDI-010976) in healthy adult subjects. The trial enrolled 30 male participants in the United States.
Yes, GS-0976 is also known as NDI-010976. Both names refer to the same investigational small molecule developed by Gilead Sciences, Inc. The Phase 1 trial NCT02876796 lists the compound under both designations.
The Phase 1 trial NCT02876796 evaluated the pharmacodynamic effects of a single oral dose of GS-0976 (NDI-010976) on fractional de novo lipogenesis in healthy adult subjects. It was a randomized, double-blind, controlled study that enrolled 30 male participants in the United States.