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Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-9674, and the Effect of Food on GS-9674 Pharmacokinetics and Pharmacodynamics

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ClinicalTrials.gov Identifier: NCT02654002
Recruitment Status : Completed
First Posted : January 13, 2016
Last Update Posted : July 27, 2016
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

This study will evaluate the safety and tolerability of escalating single- and multiple-oral doses of GS-9674, and characterize the single- and multiple-dose pharmacokinetics (PK) of GS-9674. The study will be conducted in 3 parts (Part A, Part B, and Part C). Participants will receive either GS-9674 or GS-9674 placebo.

Part A will proceed in 4 prespecified staggered cohorts. Within each cohort, the cumulative, blinded safety data will be evaluated for dose escalation from single-dose (Period 1) to multiple-dose (Period 2). Based on the available safety, pharmacokinetics, and/or pharmacodynamics (PD) data from cohorts in Part A and Part C (if applicable), total daily doses and frequency of dosing will be chosen for the cohorts in Part B. Parts B and C will consist of adaptive cohorts and may be initiated in parallel. Part B cohorts may be initiated in parallel with cohorts in Part A if the total dose under evaluation is at or below a dose already evaluated.

This study is partially blinded (no one is blinded on Day -1).


Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis (NASH) Drug: GS-9674 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GS-9674, and the Effect of Food on GS-9674 Pharmacokinetics and Pharmacodynamics
Study Start Date : January 2016
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016


Arm Intervention/treatment
Experimental: GS-9674

Part A: Participants will receive a single dose of GS-9674 during Period 1 and multiple doses of GS-9674 during Period 2.

Part B: Based on the safety and available PK and PD data from cohorts in Part A and Part C (if applicable), participants will receive up to 600 mg of GS-9674 once daily or twice a day.

Part C: Based on the safety and available PK and PD data from cohorts in Part A and Part B (if applicable), participants will receive up to 300 mg of GS-9674 once daily.

Drug: GS-9674
GS-9674 tablets administered orally

Experimental: Placebo

Part A: Participants will receive a single dose of GS-9674 placebo during Period 1 and multiple doses of GS-9674 placebo during Period 2.

Part B: Based on the safety and available PK and PD data from cohorts in Part A and Part C (if applicable), participants will receive GS-9674 placebo once daily or twice a day.

Part C: Based on the safety and available PK and PD data from cohorts in Part A and Part B (if applicable), participants will GS-9674 placebo once daily.

Drug: Placebo
GS-9674 placebo tablets administered orally




Primary Outcome Measures :
  1. Single-dose PK Parameter: AUClast of GS-9674 [ Time Frame: Up to 96 hours postdose ]
    AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.

  2. Single-dose PK Parameter: AUCinf of GS-9674 [ Time Frame: Up to 96 hours postdose ]
    AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).

  3. Single-dose PK Parameter: Cmax of GS-9674 [ Time Frame: Up to 96 hours postdose ]
    Cmax is defined as the maximum observed concentration of drug in plasma.

  4. Multiple-dose plasma PK parameter: AUCtau of GS-9674 [ Time Frame: Up to 96 hours postdose ]
    AUCtau is the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).

  5. Multiple-dose plasma PK parameter: Cmax of GS-9674 [ Time Frame: Up to 96 hours postdose ]
  6. Multiple-dose plasma PK parameter: Ctau of GS-9674 [ Time Frame: Up to 96 hours postdose ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  7. Incidence of Adverse Events [ Time Frame: Up to 15 days plus 30 days ]
  8. Proportion of Participants with 12-lead ECG Abnormalities [ Time Frame: Up to 15 days plus 30 days ]
  9. Proportion of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to 15 days plus 30 days ]

Secondary Outcome Measures :
  1. Measurement of PD Biomarker Level of Fibroblast Growth Factor 19 (FGF19) [ Time Frame: Up to 96 hours postdose ]
  2. Measurement of PD Biomarker Level of Bile Acids [ Time Frame: Up to 96 hours postdose ]
  3. Measurement of PD Biomarker Level of C4 [ Time Frame: Up to 96 hours postdose ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and non-pregnant, non-lactating female volunteers
  • Body mass index (BMI) 19 ≤ BMI ≤ 30 kg/m^2
  • Normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
  • Normal renal function (estimated glomerular filtration rate calculated using the Cockcroft-Gault equation ≥ 80 mL/min)
  • No significant medical history, and in good general health as determined by the investigator at screening evaluation performed no more than 28 days prior to the scheduled first dose

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02654002


Locations
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United States, Florida
SeaView Research, Inc
Miami, Florida, United States
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Rob Myers, MD Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02654002     History of Changes
Other Study ID Numbers: GS-US-402-1851
First Posted: January 13, 2016    Key Record Dates
Last Update Posted: July 27, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases