A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ACH-0137171 in Subjects With Chronic Hepatitis C Infection
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Multiple Doses of ACH-0137171 in Subjects With Chronic Hepatitis C Infection|
- The primary objectives of this study are as follows:
- To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection.
- To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection.
- To assess the antiviral activity of ACH-0137171 as measured by plasma HCV RNA levels in subjects with chronic hepatitis C infection following administration of multiple, escalating, oral doses.
- To assess the correlation between antiviral activity and pharmacokinetic parameters.
- The secondary objective of this study is as follows:
- To perform viral dynamic and pharmacodynamic modeling of ACH 0137171 virologic response.
- To assess the biochemical response of ACH-0137171 as measured by the change from baseline of serum ALT and AST levels.
|Study Start Date:||November 2006|
|Study Completion Date:||March 2007|
This is a randomized, double-blind, placebo-controlled, dose escalation study of ACH-0137171 in subjects with chronic HCV infection.
Sequential cohorts of 10 subjects will be randomized (8:2) to receive multiple doses of ACH-0137171 or placebo for 4 days (Days 1 through 4) with a single dose on Day 5 followed by a complete pharmacokinetic profile. Dosing will be 300 – 600 mg administered either every 12 hours or every 6 hours (maximum daily dose of 2400 mg). All doses will be administered with food.
The dose cohorts are as follows:
Cohort 1: 300 mg ACH-0137171/placebo every 12 hours (600 mg/day)* Cohort 2: 300 mg ACH-0137171/placebo every 6 hours (1200 mg/day)* Cohort 3: 600 mg ACH-0137171/placebo every 6 hours (2400 mg/day)*
A full review of all safety data will occur following each cohort. Depending on the data, the Sponsor, in consultation with the Principal Investigator(s), may consider modifying the planned dose escalation. The Sponsor may choose to interject an intermediate dose cohort between 2 planned dose escalations or repeat a given dose level, or extend the dosing period, or add an additional cohort. If a similar Grade 3 or 4 adverse event occurs in three or more subjects, and is considered to be at least possibly related to study drug, escalation to a higher dose will not occur.
Serial HCV RNA measurements, pharmacokinetic measurements of plasma concentrations of ACH-0137171, and periodic safety monitoring will occur on Days 1 through 5. Additional HCV RNA and PK measurements will be taken on Days 6 through 9. Follow up safety evaluations will be completed out to 14 days after last study drug administration (i.e., on Days 12 and 19).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00401947
|United States, Arizona|
|Mayo Clinic Hospital|
|Phoenix, Arizona, United States, 85054|
|United States, California|
|University of California, San Diego|
|LaJolla, California, United States, 92093|
|University of California, San Francisco|
|San Francisco, California, United States, 94143|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Mt. Sinai Medical Center|
|New York, New York, United States, 10029|
|United States, Texas|
|The Liver Institute at Methodist-Dallas|
|Dallas, Texas, United States, 75208|
|Alamo Medical Research|
|San Antonio, Texas, United States, 78215|
|Paraxel International GmbH|
|Berlin, Germany, BE 14050|
|Universitair Medisch Centrum Utrecht (AZU)|
|Utrecht, Netherlands, 6584 CX|
|Study Director:||John Pottage, MD||Achillion Pharmaceuticals|