The purpose of this study is to examine the safety, tolerability, pharmacokinetics (studies how the body processes a drug), and initial activity of GS-9450 in preventing liver damage due to scarring, or fibrosis, caused by Hepatitis C Virus (HCV) infection.
Approximately 32 subjects will receive GS 9450 or placebo for 14 consecutive days. Eight subjects will receive treatment within each of four dosing cohorts; 6 randomized to receive GS 9450 and two randomized to placebo: Cohort 1: GS 9450 10 mg or placebo given daily x 14 days Cohort 2: GS 9450 40 mg or placebo given daily x 14 days Cohort 3: GS 9450 80 mg or placebo given daily x 14 days If further characterization of the activity profile is deemed necessary, an additional cohort at a lower dose (5 mg) may be enrolled: Cohort 4: GS 9450 5 mg or placebo given daily x 14 days Each cohort will be conducted sequentially. Advancement to higher dose cohorts is dependent upon satisfactory safety and tolerability profiles of the preceding cohort as determined by Sponsor review (conducted in consultation with the Lead Investigator\[s\]). Progression to Cohort 4 (5 mg dose strength) will not require a safety review of Cohort 3 (80 mg dose strength); screening and randomization for Cohort 4 may begin immediately after fully enrolling Cohort 3. Alternatively, if a dose-response relationship is apparent in review of the blinded activity data from the first three cohorts, the final 5 mg cohort may be omitted.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
33
GS-9450 capsules administered orally once daily
Placebo to match GS-9450 administered orally once daily
Unnamed facility
Anaheim, California, United States
Unnamed facility
Washington D.C., District of Columbia, United States
Unnamed facility
Orlando, Florida, United States
Unnamed facility
Dallas, Texas, United States
Safety and Tolerability
Time frame: Throughout 7 weeks (2 weeks on treatment and 5 weeks post-treatment)
Plasma pharmacokinetic parameters of GS-9450 and metabolites
Time frame: 17 days (through 72 hours after last dose)
Change from baseline in alanine aminotransferase (ALT) levels at Day 14
Time frame: Day 14
Change from baseline in noninvasive markers (including cytokeratin 18 fragments) indicative of hepatic apoptosis
Time frame: Through Week 5 (2 weeks on treatment and 3 weeks post-treatment)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Unnamed facility
San Antonio, Texas, United States
Unnamed facility
Frankfurt, Germany
Unnamed facility
Hamburg, Germany
Unnamed facility
Hanover, Germany
Unnamed facility
Mainz, Germany
Unnamed facility
Würzburg, Germany
...and 1 more locations