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

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ClinicalTrials.gov Identifier: NCT00401947
Recruitment Status : Terminated (Nephrotoxicity)
First Posted : November 22, 2006
Last Update Posted : December 30, 2015
Information provided by:
Achillion Pharmaceuticals

Brief Summary:
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 or disease Intervention/treatment Phase
HCV Infection Drug: ACH-0137171 Phase 2

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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double
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
Study Start Date : November 2006
Study Completion Date : March 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. The primary objectives of this study are as follows:
  2. To assess the short-term safety and tolerability of multiple, escalating, oral doses of ACH-0137171 in subjects with chronic hepatitis C infection.
  3. To characterize the plasma pharmacokinetics of ACH-0137171 following administration of multiple, escalating, oral doses in subjects with chronic hepatitis C infection.
  4. 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.
  5. To assess the correlation between antiviral activity and pharmacokinetic parameters.

Secondary Outcome Measures :
  1. The secondary objective of this study is as follows:
  2. To perform viral dynamic and pharmacodynamic modeling of ACH 0137171 virologic response.
  3. To assess the biochemical response of ACH-0137171 as measured by the change from baseline of serum ALT and AST levels.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 (α-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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Sponsors and Collaborators
Achillion Pharmaceuticals
Study Director: John Pottage, MD Achillion Pharmaceuticals

ClinicalTrials.gov Identifier: NCT00401947     History of Changes
Other Study ID Numbers: ACH171-002
First Posted: November 22, 2006    Key Record Dates
Last Update Posted: December 30, 2015
Last Verified: December 2015

Keywords provided by Achillion Pharmaceuticals:

Additional relevant MeSH terms:
Communicable Diseases
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Antiviral Agents
Anti-Infective Agents