a study of cdi-31244: a novel nni in hv and hcv infected subjects

Conditions: Hepatitis C

Summary: this is a first in human study of orally administered cdi-31244, a non-nucleoside inhibitor (nni) in healthy volunteers and hcv infected individuals

this is a single center, double-blind, placebo-controlled, randomized, single ascending oral dose and multiple oral dose design, incorporating fed/fasted comparisons. the study will include two groups: group a - single ascending dose (sad) including a food effect cohort, and multiple dose (md) in healthy volunteers (hv), and group b md in hepatitis c virus (hcv) infected individuals divided in two parts. five single-dose cohort are planned. for the five single-dose cohorts, a sentinel group of 2 subjects will be dosed at least one day prior to enrolling remaining subjects. six multiple-dose cohorts are planned. three multiple dose cohorts in healthy volunteers and three cohorts in hcv-infected individuals. the dosing of group b will be conducted following safety and pharmacokinetic (pk) review of group a. the dosing of group b, part 2 will be conducted only if part 1 shows acceptable safety and efficacy results.

Eligibility criteria:
main inclusion criteria: hv and hcv infected subjects: * male or female aged ≥ 18 to ≤ 65 years; * body mass index ≥ 18.5 to ≤ 35.0 kg/m2; * body weight ≥ 50 kg; * negative screening for alcohol and drugs of abuse; * normal results on 12-lead electrocardiogram (ecg); * for females, negative result on a pregnancy test. hcv infected subjects: * hcv treatment-naïve subjects must have not received prior direct acting agent (daa) treatment for hepatitis c infection; * documented clinical history compatible with chronic hepatitis c; * hcv genotype 1 by hcv genotyping performed at screening; * plasma hcv rna ≥ 5.0 log10 iu/ml at screening; * laboratory evidence of no cirrhosis (negative liver biopsy or fibroscan or fibrotest, f2 or lower) within one year prior to study), if these are not available, do a fibrotest at screening, which must be f2 or lower. main exclusion criteria: hv and hcv infected subjects: * females who are pregnant or are lactating; * co-infected with hepatitis b virus (hbv, hbsag positive) and/or human immunodeficiency virus (hiv); * abuse of alcohol and/or drugs that could interfere with adherence to study requirements as judged by the investigator; * positive screen result for drugs of abuse or alcohol on day -1. use of other investigational drugs within 60 days of dosing; * subject with intestinal malabsorption; * presence of out-of-range cardiac interval on the screening ecg or other clinically significant ecg abnormalities; * serum creatinine \> upper limit of normal (uln); * 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. healthy volunteers: * positive screen for anti-hcv antibody hcv infected subjects: * clinical (in the opinion of the investigator) or laboratory evidence of cirrhosis; * history or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency; * history of hepatocellular carcinoma (hcc) or findings suggestive of possible hcc; * active clinically significant diseases.

Keywords: non-nucleoside inhibitor nni hcv daa