Study of CTS-1027 in Hepatitis C Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine if CTS-1027 can lower elevated liver enzymes in patients with chronic HCV infection.

Detailed Description
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Randomized, placebo-controlled, double-blind, parallel group, multicenter, dose response trial utilizing four doses of CTS-1027, administered orally once daily, in outpatients with chronic hepatitis C virus (HCV) infection.

Official Title
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A Dose Response Study of CTS-1027 in Hepatitis C Patients

Conditions
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Chronic Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: CTS-1027
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients of minimum adult legal age (according to local laws for signing the informed consent document), able to provide written informed consent, and understand and comply with the requirements of the trial A history of chronic HCV infection Unsuccessful HCV treatment defined as one or more of the following criteria: Failure to achieve a virologic response during previous therapy, or Failure to tolerate therapy, or Failure to maintain a sustained virologic response, or In the opinion of the Principal Investigator, the patient is not a suitable candidate for interferon based therapy Liver impairment, as defined by either aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels 1.5 - 7 x ULN on at least two occasions, seven or more days apart, during the baseline period Alpha-fetoprotein (AFP) <= 50 ng/mL Hemoglobin >= 10 g/dL, platelet count >= 75 x 109/L, and white blood cell count >= 1.5 x 109/L Willingness to utilize adequate contraception (if female, evidenced by being postmenopausal for at least 6 months or using contraceptive pill; for both females and males, being surgically sterile, or using two forms of barrier contraception) from screening to at least one month after the completion of the trial. Exclusion Criteria: Decompensated or severe liver disease defined by one or more of the following criteria: Prior liver biopsy showing cirrhosis Prior liver biopsy showing bridging fibrosis (Metavir >2 or Ishak >3) more than 2 years ago in the absence of newer liver biopsy results Prothrombin time: 3 seconds > control Total bilirubin >= 1.5 x Upper limit of the normal range (ULN), or > 3 x ULN for unconjugated bilirubin Serum albumin below normal limits AST or ALT > 7 x ULN during baseline period Evidence of portal hypertension including: Splenomegaly or evidence of portal hypertension (i.e., enlarged portal vein and varices) on ultrasound, Varices in esophagogastroduodenoscopy (EGD); or Ascites Hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound (or other imaging techniques) Known history or presence of human immunodeficiency virus (HIV) infection Co-infection with hepatitis B virus (HBV) If female: pregnant, lactating, or positive serum or urine pregnancy test Last baseline AST and ALT level prior to Day 1 of < 1.5 x ULN Renal impairment (creatinine > 1.5 x ULN) or hepatorenal syndrome Pancreatitis Hospitalization for liver disease within 60 days of screening Use of concomitant or prior drug therapy for HCV at screening, including the use of: drugs with presumed anti-HCV activity in the prior three months corticosteroids in the past 30 days potentially hepatotoxic drugs in the past 30 days (including alpha methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin) Use of illicit or drugs of abuse in the prior three months (allowed if medically prescribed or indicated) History of alcohol abuse within the past year History or presence of clinically concerning cardiac arrhythmias or prolongation of pre-dose QT or QTc interval of > 450 milliseconds Other concomitant disease or condition likely to significantly decrease life expectancy (e.g., moderate to severe congestive heart failure) or any malignancy other than curatively treated skin cancer (basal cell or squamous cell carcinomas), unless adequately treated or in complete remission for ten or more years Any patient who has received any investigational drug or device within 30 days of dosing, or who is scheduled to receive another investigational drug or device during the course of this trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2.5 milligram (mg) CTS-1027<br>2.5 mg CTS-1027 | Drug: CTS-1027<br>* Eligible patients were randomized to one of four doses of CTS-1027 (2.5 mg, 5 mg, 10 mg, or 30 mg) or placebo qd (quaque die, once daily).<br>|
| Experimental: 5 mg CTS-1027<br>5 mg CTS-1027 | Drug: CTS-1027<br>* Eligible patients were randomized to one of four doses of CTS-1027 (2.5 mg, 5 mg, 10 mg, or 30 mg) or placebo qd (quaque die, once daily).<br>|
| Experimental: 10 mg CTS-1027<br>10 mg CTS-1027 | Drug: CTS-1027<br>* Eligible patients were randomized to one of four doses of CTS-1027 (2.5 mg, 5 mg, 10 mg, or 30 mg) or placebo qd (quaque die, once daily).<br>|
| Experimental: 30 mg CTS-1027<br>30 mg CTS-1027 | Drug: CTS-1027<br>* Eligible patients were randomized to one of four doses of CTS-1027 (2.5 mg, 5 mg, 10 mg, or 30 mg) or placebo qd (quaque die, once daily).<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Eligible patients were randomized to one of four doses of CTS-1027 (2.5 mg, 5 mg, 10 mg, or 30 mg) or placebo qd.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events at each dose level |  | 4 to 24 weeks | 
| Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels at each dose |  | 4-24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak and trough levels of CTS-1027 in plasma |  | 4 to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, HCV treatment failure, Elevated aminotransferases