A first-in-human trial of IDX21437, a new study drug being evaluated for hepatitis C virus infection.

Phase 1

• Conditions: MedDRA version: 16.1Level: LLTClassification code 10019751Term: Hepatitis C virusSystem Organ Class: 100000004848; Hepatitis C virus; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2013-004043-23-BE
• Lead Sponsor: Idenix Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-10-03
• Last Update Posted: 22 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Read and signed the written informed consent form (ICF) after the nature of the study has been fully explained.
2. Male or female subjects between 18 and 65 years of age, inclusive (or the legal age of consent per local regulations).
3. Minimum body weight of 50 kg and body mass index (BMI) of 18-32 kg/m2 (Group A) or 18-35 kg/m2 (Groups B-E), inclusive.
4. All subjects of childbearing potential must have agreed to use a double-method of birth control (one of which must be a barrier) from Screening through at least 90 days after the last dose of the study drug.
Non-childbearing potential is defined as:
• Females: postmenopausal, defined as amenorrheic for at least 2 years and serum follicle stimulating hormone (FSH) level consistent with postmenopausal status at Screening, or a self-reported hysterectomy, bilateral oophorectomy or bilateral tubal ligation at least 6 months prior to Screening.
• Males: a self-reported vasectomy at least 6 months prior to Screening.
5. Females must have a negative serum beta-human chorionic gonadotropin (ß-HCG) at Screening and a negative pregnancy test (urine or ß-HCG) at Day -1.
6. Male subjects must have agreed not to donate sperm from the first dose through 90 days after the last dose of study drug.
7. Subject must not have consumed grapefruit or grapefruit juice within 7 days of reporting to the clinic on Day -1, and agrees not to do so through the end of the study.
8. Subject is, in the opinion of the investigator, willing and able to comply with the study drug regimen and all other study requirements.
Group A Specific (must also meet the following)
9. Subject must not have smoked or used nicotine-containing products within 6 months prior to Day -1 and agrees not to do so for the duration of the study.
Groups B, C, D and E Specific (must also meet the following)
10. Subjects in Group B may have received prior treatment with interferon (IFN) and ribavirin for hepatitis C infection but not treatment with any direct-acting antivirals (DAA). Subjects in Groups C, D and E must be HCV treatment-naïve (i.e., no prior exposure to any antiviral treatment for hepatitis C infection).
11. Documented clinical history compatible with chronic hepatitis C, including any one of the following:
• anti- HCV antibody positive at least 6 months prior to Screening or dosing, OR
• HCV genotype results at least 6 months prior to Screening or dosing, OR
• HCV RNA present in plasma by a sensitive and specific assay at least 6 months prior to Screening or dosing, OR
• Histologic evidence of chronic hepatitis C infection
12. HCV Genotype 1, 2, 3, 4, 5 or 6 by HCV genotyping performed at Screening (genotype dependent on the group/cohort enrolling). Note: For a specific genotype, mixed subtypes are acceptable but mixed genotypes are not.
13. Plasma HCV RNA = 5.0 log10 IU/mL at Screening.
Group E Specific (must also meet the following)
14. Subjects must be Child-Pugh Class A.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 132
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

1.Female subject is pregnant or breastfeeding.
2. Co-infected with hepatitis B virus (HBV, HBsAg positive) and/or human immunodeficiency virus (HIV).
3. Donated more than 500 mL of blood or had significant blood loss 60 days prior to dosing.
4.Abuse of alcohol and/or drugs that could interfere with adherence to study requirements as judged by the investigator.
5.Positive screen result for drugs of abuse or alcohol at Screening or on Day –1.
6.Concomitant use of any known major inhibitor or inducer of cytochrome P450 (CYP) 3A4. A washout period of at least 5 half-lives of the CYP 3A4 drug must be observed prior to study drug dosing, if the investigator feels that the drug can be safely discontinued or substituted for the duration of the study.
7.Concomitant use of herbal or dietary supplements. A washout period of at least 7 days must be observed prior to study drug dosing.
8.Concomitant use of acid blockers (e.g., proton-pump inhibitors). A washout period of at least 5 half-lives must be observed prior to study drug dosing, if the investigator feels that the drug can be safely discontinued or substituted for the duration of the study. Antacids (stomach acid neutralizers such as calcium carbonate or aluminum hydroxide-based products) will be allowed during the study, except ±4 h of dosing.
9.Concomitant use of the following medications: amlodipine, aripiprazole, atorvastatin, carvedilol, diazepam, diltiazem, fluoxetine, isradipine, perphenazine, procainamide, simvastatin, thioridazine or verapamil. A washout period of at least 5 half-lives must be observed prior to initiating study drug dosing, if the investigator feels that the drug can be safely discontinued or substituted for the duration of the study.
10.Use of other investigational drugs within 60 days of dosing, or plans to enroll in another clinical trial of an investigational agent while participating in the present study.
11.Subject with intestinal malabsorption (e.g., structural defects, digestive failure or enzyme deficiencies with the exception of lactose intolerance).
12.Subject with known allergy to the study medication or any of its components.
13.Cardiac disease, family history of congenital heart disease, family history of prolonged QT, or family history of sudden death of unknown etiology.
14.One or more of the following abnormalities:
•First degree, or greater, heart block.
•QTcF interval = 430 ms for males or = 450 ms for females, at Screening, Day -1 and Day 1 (prior to the first dose).
•Clinically significant abnormal ECG at Screening or Day -1, as determined by the investigator.
15.At Screening or Day -1: an estimated glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 as estimated by the Modification of Diet in Renal Disease (MDRD) formula.
16.Hemoglobin (Hgb) < 13.0 g/dL for males, < 12.0 g/dL for females.
17.Any clinically significant medical condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results.
Group A Specific (following also excluded)
18.Concomitant use of prescription medications, or systemic over-the-counter 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.
19.Abnormal laboratory values at Screening or Day -1 that are considered to be clinically significant by the investigator(s).
20.Positive sc

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • Safety and tolerability<br>• Plasma and urine pharmacokinetics (PK)<br>• The effect of food on the PK of IDX21437<br>• Antiviral activity<br>;Secondary Objective: NA;Primary end point(s): plasma PK samples<br>urine PK samples;Timepoint(s) of evaluation of this end point: see protocol Tables 7-4, 7-5 & 7-6

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): PK endpoints=plasma and urine concentrations of IDX21437 and metabolites<br><br>Safety endpoints=adverse events and laboratory abnormalities<br><br>Antiviral activity endpoints=change in HCV RNA viral load;Timepoint(s) of evaluation of this end point: see Tables 7-1 through 7-6.<br>