Safety and clinical effects of IDX320 in Hepatitis C infectio
- Conditions
- Genotype 1 Chronic Hepatitis CInfections and InfestationsChronic viral hepatitis
- Registration Number
- ISRCTN44746369
- Lead Sponsor
- Idenix Pharmaceuticals (USA)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 88
1. 18-65 years of age, inclusive (or the legal age of consent per local regulations)
2. Body Mass Index (BMI) 18-35 kg/m2
3. Male subjects must have agreed to use a consistent form of an acceptable double-barrier method of birth control
4. Pulse = 40 beats per minute (BPM), systolic blood pressure = 95 mmHg and QTcF interval = 450 ms at screening and Day -1
5. Subject has provided written informed consent to participate in the study
Part A Specific (must also meet the following)
6. Subject must be male.
Part C and D Specific (must also meet the following)
7. HCV treatment-naïve ? subject must have not received prior antiviral treatment for hepatitis C infection
Parts B, C and D Specific (must also meet the following)
8. Male or female subjects may be included. If female, subject must be of non-childbearing potential.
9. Documented clinical history compatible with chronic hepatitis C, including any one of the following:
9.1. anti-HCV antibody positive at least six months prior to screening or dosing OR
9.2. HCV ribonucleic acid (RNA) present in plasma by a sensitive and specific assay at least six months prior to screening or dosing OR
9.3. Histologic evidence of chronic hepatitis C infection (Note: Subjects with cirrhosis are excluded)
10. Plasma HCV RNA = 5 log10 IU/mL at screening
11. HCV genotype 1 by HCV genotyping performed at screening
Initial information at time of registration:
1. Co-infected with hepatitis B virus (HBV, HBsAg positive) and/or human immunodeficiency virus (HIV)
2. Donated blood or had significant blood loss 60 days prior to dosing
3. Use of alcohol and/or drugs that could interfere with adherence to study requirements as judged by the investigator
4. Positive screen result for drugs of abuse (except THC) or alcohol on Day ?1
5. Concomitant use of any known major inhibitor or inducer of cytochrome P450 3A4 (CYP 3A4)
6. Use of other investigational drugs within 60 days of dosing, or plans to enrol in another clinical trial of an investigational agent while participating in the present study
7. Subject with intestinal malabsorption (e.g., structural defects, digestive failure or enzyme deficiencies with the exception of lactose intolerance)
8. Subject with known allergy to the study medication or any of its components
9. Clinically significant abnormal electrocardiogram (ECG) at screening or Day -1
10. Serum creatinine > Upper Limit of Normal (ULN)
11. Estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 as estimated by the Modification of Diet in Renal Disease (MDRD) formula
PART A Specific (following also excluded)
12. History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the Clinical Unit OR history of smoking within 24 hours prior to admission to the Clinical Unit
13. Any clinically significant medical condition that, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results
14. Concomitant use of prescription medications or systemic over-the-counter (OTC) medications. A washout period of at least 5 half-lives must be observed prior to study drug dosing, if the investigator feels that the medication can be safely discontinued for the duration of the study.
15. Abnormal laboratory values at screening or Day -1 that are considered to be clinically significant by the Principal Investigator(s)
16. Positive screen for anti-HCV antibody
PART B Specific (following also excluded)
17. Subject received pegylated interferon and ribavirin within 6 months of screening
PART B, C and D Specific (following also excluded)
18. Subject is pregnant or breastfeeding. Women must have a negative serum beta-human chorionic gonadotropin (ß-HCG) at screening and Day -1.
19. History or signs of decompensated liver disease: Child-Pugh class B or C, ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency
20. Prior clinical or histological evidence of cirrhosis (e.g. Metavir 4 or Ishak 6)
21. History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC
22. Active clinically significant diseases including:
22.1. Primary or secondary causes of liver disease (other than hepatitis C)
22.2. Malignant disease or suspicion or history of malignant disease within previous 5 years (except for adequately treated basal cell carcinoma)
22.3. Diabetes mellitus requiring treatment with medication
22.4. Any other condition that, in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results
23. Previously received any other experimental direct-acting antiviral agents targeting the hepatitis C virus (e.g. HCV polymerase or protease inhibitors).
24.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Safety and tolerability: <br>1.1. Adverse events, recorded at all study visits ie. Days 1-6 or 10<br>1.2. Physical examination performed at screening and Day 6 or 10 (depending on the Part of the study)<br>1.3. Vital signs, recorded at all study visits ie. Days 1-6 or 10<br>1.4. 12-lead ECG, performed at screening, Days -1, 1, 2, 4 and 6 for the single dose cohorts and at screening, Days -1, 1, 2, 3, 4, 7 and 10 for the multiple dose cohorts<br>1.5. Standard safety laboratory tests, performed at screening, Days -1, 1, 2, 4 and 6 for the single dose cohorts and at screening, Days -1, 1, 2, 3, 4, 7 and 10 for the multiple dose cohorts<br>2. Antiviral activity, measured at all study visits ie. Days 1-6 or 10 except Day 9: <br>2.1. Change in plasma HCV RNA <br>2.2. Emergence of resistance mutations
- Secondary Outcome Measures
Name Time Method 1. Pharmacokinetics: <br>1.1. Plasma and urine PK of IDX320<br>2. Food effect