A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Oral ACH-0143422 after Single and Multiple-ascending Doses in Health Volunteers and Subjects With Chronic Hepatitis C Virus Genotype 1 Infection.
Achillion Pharmaceuticals, Inc
157 participants
Apr 30, 2014
Interventional
Conditions
Summary
This study is divided into three phases. The first two phases are being conducted in healthy volunteers. The third phase will be conducted in patients who have been diagnosed with Hepatitis C genotype 1. The first phase of the study will evaluate the safety, tolerability and pharmacokinetics of four single doses of ACH 0143422 or placebo (50mg, 150mg, 300mg or 500mg). This first part will also examine the different absorption rates between fed and fasted groups and these results will inform how patients are dosed in the rest of the trial. The second phase will evaluate the safety ,tolerability and pharmacokinetics of four different dosing regiments of ACH0143422 or placebo (50mg, 150mg, 300mg or 500mg) taken once a day for 14 days. The third phase of the study will be conducted in HCV positive patients and will evaluate safety ,tolerability and pharmacokinetics of four different dosing regimens of ACH0143422 or placebo (50mg, 150mg, 300mg or 500mg) taken once a day for 7 days. It will also examine the effect the study drug/placebo has on the HCV viral load.
Eligibility
Inclusion Criteria9
- Between 18 and 55 years old
- No clinically relevant health abnormalities
- Agree to use effective contraception (defined in the protocol)4. HCV GT-1 (Groups 9, 10, 11, 12A and 12B), HCV GT-3 (Group 12C) and HCV GT-2 (Group 12D) including all subtypes, mixed subtypes or subtypes undetermined
- Body mass index of 18 to 30 kg/m2 with a minimum body weight of 50 kg
- Aged 18 to less than 70 years old
- Treatment naive subjects with chronic HCV infection
- BMI of 18 to 36 kg/m2 with a minimum body weight of 50 kg
- HCV genotype 1 (including 1a, 1b, or mixed subtypes of genotype 1)
- HCV RNA greater or equal to 10,000 IU/mL at screening
Exclusion Criteria12
- History of any clinically relevant illness or clinically significant laboratory abnormalities or ECG (defined in the protocol)
- Pregnant or nursing females
- Febrile illness within 7 days of first dose of study drug
- Current Smoker
- Positive urine drug screen at day 0-1
- Regular alcohol consumption
- Any condition possibly affecting drug absorption (e.g., gastrectomy)
- Use of prescription drugs, non-prescription drugs, dietary supplements, herbal supplements, and hormonal therapy/replacement, or ingestion of foods which are CYP3A4 substrates, inducers and inhibitors within 14 prior to the first dose of study medication unless approved by the Investigator and Sponsor
- As above and also including:
- History of participation in a clinical trial with a polymerase inhibitor or previous treatment with a polymerase inhibitor, where at least one dose of the polymerase inhibitor was consumed. Subjects who were dosed with placebo on a clinical trial may be enrolled in this study
- Co-infection with HIV-1, HIV-2 or HBV
- Subjects with a history of liver disease
Interventions
Active treatment is ACH-0143422 or placebo taken at the following dosages and frequencies: In healthy volunteers: Group 1A: single dose of 50mg FED Group 1B: single dose of 50mg FASTED Group 2A: single dose of 150mg FED Group 2B: single dose of 150mg FASTED Group 3: single dose of 300 mg FED Group 4A: single dose of 500 mg FED Group 4B: single dose of 700 mg FED Group 5: 50mg, once daily for 14 days Group 6: up to 150mg, once daily for 14 days Group 7: up to 300mg, once daily for 14 days Group 8A: 500 mg, once daily for 14 days FASTED Group 8B: 500 mg, once daily for 14 days FED Group 8C: 700 mg, once daily for 14 days FED In Hepatitis C patients: Group 9: 50mg, once daily for 7 days Group 10: up to 150mg, once daily for 7 days Group 11: up to 300mg, once daily for 7 days Group 12A: 500 mg, once daily for 14 days FED Group 12B: 700 mg, once daily for 14 days FED Group 12C: GT3 subjects, 700 mg, once daily for 14 days FED Group 12D: GT2 subjects, 700 mg, once daily for 14 days FED Groups 3-12D will be either fed or fasted, depending on the results from previous groups. ACH 0143422 or placebo will be administered orally for all participants in all parts of the trial. All treatments for healthy volunteers and treatments up to Day 8 for HCV patients will be administered in the clinic to ensure compliance.
Locations(1)
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ACTRN12614000304639