A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ACH-0137171 in Subjects With Chronic Hepatitis C Infection

This study has been terminated.
(Nephrotoxicity)
Sponsor:
Information provided by:
Achillion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00401947
First received: November 17, 2006
Last updated: May 10, 2007
Last verified: May 2007
  Purpose

The purpose of this study is to Investigate the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Multiple Doses of ACH-0137171 in Subjects with Chronic Hepatitis C Infection


Condition Intervention Phase
HCV Infection
Drug: ACH-0137171
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Achillion Pharmaceuticals:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • 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.

Estimated Enrollment: 30
Study Start Date: November 2006
Study Completion Date: March 2007
Detailed Description:

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:

Study Schema:

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).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic HCV infection must be documented by positive anti HCV antibody using a third generation enzyme immunoassay (EIA) and persistent detection of HCV RNA in the blood for at least 6 months. Subjects must be infected with HCV genotype 1 (line probe assay; INNO-LiPA HCV II, Innogenetics) and may be treatment-naïve or treatment-experienced (treatment experienced specifically means prior treatment with interferon, standard or pegylated, with or without ribavirin with therapy stopped > 6 months prior to screening). In addition, eligible subjects must have ALT and AST < 5 x upper limit of normal (ULN), plasma HCV RNA> 5 log10 IU/mL, and have no clinical or laboratory evidence of hepatic decompensation for inclusion (must have platelets >100,000/mm3, total bilirubin < 1.5 x ULN, prothrombin time < 1.5 x ULN, or albumin > 3.0 g/dL for inclusion). Women are eligible if not pregnant or breast-feeding. Women of childbearing potential (i.e., not surgically sterile or confirmed post menopausal) must have confirmed negative pregnancy tests. All subjects must practice a medically acceptable form of contraception described in Section 7.2.1.

Exclusion Criteria:

  • HIV or HBV co-infection, known cirrhosis, prior history of clinical hepatic decompensation (ascites, jaundice, encephalopathy or variceal hemorrhage), alcoholic or other forms of chronic liver disease, evidence of hepatocellular carcinoma (-fetoprotein > 50 ng/mL), creatinine clearance < 80 mL/min (using Cockcroft-Gault equation), hemoglobin < 10 g/dL, neutrophils < 1500/mm3, abnormal thyroid function tests (TSH > 2.5 µIU/mL, free T4 > ULN), or, a positive test result for illicit drugs, alcohol, or drug abuse within the past 12 months. Subjects who have significant gastrointestinal, thyroid, renal, cardiovascular, pulmonary, oncologic, or neurological disease, or who are currently receiving immunomodulators (corticosteroids, etc), investigational, nephrotoxic or hepatotoxic drugs (e.g phenytoin, carbamazepine, INH, azole anti-fungal agents such as ketoconazole, and aminoglycoside antibiotics, etc.), non-steroidal anti-inflammatory agents, ibuprofen or acetaminophen (on a daily basis) will also be excluded.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00401947

Locations
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
Germany
Paraxel International GmbH
Berlin, Germany, BE 14050
Netherlands
Universitair Medisch Centrum Utrecht (AZU)
Utrecht, Netherlands, 6584 CX
Sponsors and Collaborators
Achillion Pharmaceuticals
Investigators
Study Director: John Pottage, MD Achillion Pharmaceuticals
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00401947     History of Changes
Other Study ID Numbers: ACH171-002
Study First Received: November 17, 2006
Last Updated: May 10, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by Achillion Pharmaceuticals:
HCV
Chronic
Hepatitis

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014