E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To investigate the safety and tolerability of multiple oral doses of GS-9450 in subjects with chronic hepatitis C (HCV).
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E.2.2 | Secondary objectives of the trial |
• To investigate the pharmacokinetics of multiple oral doses of GS 9450 and its metabolites in subjects with chronic HCV
• To investigate the activity of multiple oral doses of GS 9450 in subjects with chronic HCV, as evidenced by: (1) change from baseline in alanine aminotransferase (ALT) levels (primary activity measure), (2) change in aspartate aminotransferase (AST) levels, and (3) change in noninvasive markers indicative of hepatic apoptosis, including cytokeratin 18 caspase-cleavage fragment [CK-18])
• To investigate the effects of GS 9450 on hepatitis C viral load
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Adult subjects, ages 18-65 infected with chronic HCV of any genotype who have previously failed treatment with PEG in combination with RIBA. • Potential subjects must not have hepatic cirrhosis; the absence of cirrhosis must be confirmed by either a liver biopsy performed within one year prior to the screening visit or concordant results from a FibroTest® and a Fibroscan® both performed within one year prior to the screening visit. • ALT ≥ 1.5 x ULN but < 10 x ULN • BMI between 19 and 32 kg/m2 (inclusive) • Creatinine clearance ≥ 70 mL/min • absolute neutrophil count ≥ 1000/mm3 • hemoglobin ≥ 10 g/dL • have no clinical or laboratory evidence of hepatic decompensation (i.e., subjects must have platelets ≥ 75,000/mm3, total bilirubin ≤ 1.5 x ULN, prothrombin time ≤ 1.5 x ULN and albumin ≥ 3.0 g/dL). |
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E.4 | Principal exclusion criteria |
• decompensated liver disease • evidence of hepatocellular carcinoma (i.e., alpha-fetoprotein 50 ng/mL) • prior diagnosis of cirrhosis • positive urine drug screen for opiates, cocaine or amphetamines • co-infection with hepatitis B virus (HBV) • human immunodeficiency virus (HIV); pancreatitis • recent significant infection or symptoms of infection (including mononucleosis or active herpes simplex virus) • autoimmune disorders • transplantation • history of malignancy • ongoing alcohol abuse (defined as intake of more than 28 units of alcohol per week |
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E.5 End points |
E.5.1 | Primary end point(s) |
• The primary safety endpoint will evaluate the tolerability of multiple oral doses of GS-9450. This endpoint will be assessed as treatment limiting adverse events or laboratory abnormalities that require premature discontinuation from the study.
• The primary activity endpoint will be change from baseline in ALT levels at Day 14.
• The primary pharmacokinetic endpoints of this study are to characterize the plasma PK parameters of GS-9450 and metabolites following multiple doses of GS-9450 using standard non compartmental methods. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LPLV will be defined as date of last Week 26 follow-up visit for last patient of the final cohort.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |