A Phase Ia/Ib Study Assessing Single and Multiple Doses of CDI-31244: A Non-Nucleoside Inhibitor in Healthy and Hepatitis C Virus-Infected Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Number of treatment emergent adverse events (AE)
研究概览
简要总结
This is a First in Human study of orally administered CDI-31244, a non-nucleoside inhibitor (NNI) in healthy volunteers and HCV infected individuals
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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 -
- •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.
研究组 & 干预措施
Cohort 1A HV
CDI-31244 20 mg active or placebo single dose (SD)
干预措施: CDI-31244 (Drug)
Cohort 1A HV
CDI-31244 20 mg active or placebo single dose (SD)
干预措施: Placebo (Drug)
Cohort 2A HV
CDI-31244 50 mg active or placebo SD
干预措施: CDI-31244 (Drug)
Cohort 2A HV
CDI-31244 50 mg active or placebo SD
干预措施: Placebo (Drug)
Cohort 5A HV
CDI-31244 400 mg active or placebo SD
干预措施: Placebo (Drug)
Cohort 3A HV
CDI-31244 100 mg active or placebo SD
干预措施: CDI-31244 (Drug)
Cohort 3A HV
CDI-31244 100 mg active or placebo SD
干预措施: Placebo (Drug)
Cohort 4A HV
CDI-31244 200 mg active or placebo SD; food effect
干预措施: CDI-31244 (Drug)
Cohort 4A HV
CDI-31244 200 mg active or placebo SD; food effect
干预措施: Placebo (Drug)
Cohort 5A HV
CDI-31244 400 mg active or placebo SD
干预措施: CDI-31244 (Drug)
Cohort 6A HV
CDI-31244 200 mg active or placebo multiple dose (MD)
干预措施: CDI-31244 (Drug)
Cohort 6A HV
CDI-31244 200 mg active or placebo multiple dose (MD)
干预措施: Placebo (Drug)
Cohort 7A HV
CDI-31244 200 mg active or placebo MD
干预措施: CDI-31244 (Drug)
Cohort 7A HV
CDI-31244 200 mg active or placebo MD
干预措施: Placebo (Drug)
Cohort 8A HV
CDI-31244 400 mg active or placebo MD
干预措施: CDI-31244 (Drug)
Cohort 8A HV
CDI-31244 400 mg active or placebo MD
干预措施: Placebo (Drug)
Cohort 1B HCV genotype (GT) 1
CDI-31244 400 mg active or placebo MD
干预措施: CDI-31244 (Drug)
Cohort 1B HCV genotype (GT) 1
CDI-31244 400 mg active or placebo MD
干预措施: Placebo (Drug)
Cohort 2B HCV GT 1
CDI-31244 600 mg active or placebo MD
干预措施: CDI-31244 (Drug)
Cohort 2B HCV GT 1
CDI-31244 600 mg active or placebo MD
干预措施: Placebo (Drug)
Cohort 3B HCV GT 1
CDI-31244 800 mg active or placebo MD
干预措施: CDI-31244 (Drug)
Cohort 3B HCV GT 1
CDI-31244 800 mg active or placebo MD
干预措施: Placebo (Drug)
结局指标
主要结局
Number of treatment emergent adverse events (AE)
时间窗: Day 1 to Day 35
The safety and the tolerability of single and multiple oral doses of CDI-31244 through number of AEs observed in HV and HCV infected subjects
次要结局
- Measure plasma levels of CDI-31244 after SD(Day 1 to Day 6)
- Measure plasma levels of CDI-31244 after SD in fasted and fed conditions(Day 1 to Day 13)
- Measure plasma levels of CDI-31244 after MD(Day 1 to Day 13)
- Measure HCV mutation through genotyping at baseline and after CDI-31244 dosing(Day 1 to 35)
- Measure HCV viral load through the RNA quantitative test(Day 1 to Day 35)