Evaluation of IDX375 in healthy and hepatitis C-infected subjects

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN80501908
• Date of registration: 26/08/2010
• Prospective Registration: No
• Primary sponsor: Idenix Pharmaceuticals, Inc. (USA)
• Public title: Evaluation of IDX375 in healthy and hepatitis C-infected subjects
• Scientific title: A phase I/IIa study assessing single and multiple doses of hepatitis C virus (HCV) non-nucleoside polymerase inhibitor IDX375 in healthy and genotype 1 HCV-infected subjects
• Date of first enrolment: 09/06/2010
• Target sample size: 78
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN80501908
• Study type: Interventional
• Study design: Two part randomised double-blind placebo controlled dose escalation and proof-of-concept trial (Treatment)

Countries of recruitment

Belgium, Moldova

Contacts

• Name: John Sullivan-Bólyai

Key inclusion & exclusion criteria

Inclusion criteria: All participants:
1. Aged 18 - 65 years
2. Body mass index (BMI) 18 - 35 kg/m^2
3. Must agree to use an acceptable double-barrier method of birth control
4. Male subject must agree not to donate sperm for 90 days after the last dose of study drug
5. Subject has provided written informed consent to participate in the study

Specific to healthy subjects:
6. Subject must be male
7. Subject must be a non-smoker

Specific to HCV-infected subjects:
8. Female subjects must be of non-childbearing potential
9. Documented clinical history compatible with chronic hepatitis C
10. Plasma HCV ribonucleic acid (RNA) greater than or equal to 5 log10 IU/mL at screening
11. HCV genotype 1
12. HCV treatment-naive
Exclusion criteria: All participants:
1. Co-infected with hepatitis B virus 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. 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
5. Subject with known allergy to the study medication or any of its components
6. Clinically significant laboratory or electrocardiogram (ECG) abnormalities
7. Any clinically significant medical condition that, in the opinion of the Investigator, would jeopardise the safety of the subject or impact the validity of the study results

Specific to healthy subjects:
8. 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.
9. Positive screen for anti-HCV antibody

Specific to HCV-infected subjects:
10. Subject is pregnant or breastfeeding
11. 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
12. History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Genotype 1 chronic hepatitis C virus
Infections and Infestations
Chronic viral hepatitis

Intervention(s)

1. Dose escalation in healthy subjects - 8 subjects per dosing cohort, randomised 6:2 (active:placebo):
1.1. 200 mg IDX375 (or placebo) x 1 day
1.2. 400 mg IDX375 (or placebo) on days 1 and 8
1.3. 300 mg IDX375 (or placebo) x 1 day
1.4. 1200 mg IDX375 (or placebo) x 1 day
1.5. 800 mg IDX375 twice daily (BID) or (placebo BID) x 1 day
1.6. 800 mg IDX375 BID or (placebo BID) x 3 days

2. Proof-of-concept in HCV-infected subjects - 10 subjects per dosing cohort, randomised 8:2 (active:placebo):
2.1. 400 mg IDX375 BID or (placebo BID) x 3 days
2.2. 800 mg IDX375 BID or (placebo BID) x 3 days
2.3. 1200 mg IDX375 four times a day (QD) or (placebo QD) x 3 days

Total duration of treatment: maximum 3 days dosing
Total duration of follow-up: maximum 25 days follow-up

Primary Outcome(s)

1. Adverse events, physical examination, vital signs, electrocardiograms (ECGs), standard safety laboratory tests
2. Change in plasma HCV RNA, emergence of resistance mutations

Measured daily during research unit confinement up to 14 days maximum, with weekly visits for follow-up.

Secondary Outcome(s)

Plasma concentrations of IDX375. Measured daily during research unit confinement up to 14 days maximum, with weekly visits for follow-up.

Secondary ID(s)

IDX-09B-001

Source(s) of Monetary Support

Idenix Pharmaceuticals, Inc. (USA)