NCT02604355终止1 期
A Multiple-Center, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose and Multiple-Ascending Dose, Adaptive Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7020322 Following Oral Administration in Healthy Subjects and Chronic Hepatitis B Patients
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 49
- 试验地点
- 4
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
This is a multiple-center, randomized, double-blind, placebo-controlled, single-ascending dose and multiple-ascending dose, adaptive parallel study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020322 following oral administration in healthy participants and chronic hepatitis B patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- •Healthy Participants' Inclusion Criteria:
- •A Body Mass Index (BMI) between 18 to 30 kg/m^2, inclusive, and a body weight of at least 50 kg
- •Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm during the study
- •Women should be of non-childbearing potential
- •Able to comply with study restrictions
- •Non-smoker (nor tobacco-containing products) for at least 90 days prior to dosing on Day 1 and agreeing not to smoke during the study
- •Chronic Hepatitis B-Infected Participants' Inclusion Criteria:
- •Chronic hepatitis B infection
- •A BMI between 18 to 32 kg/m^2, inclusive
- •Positive test for HBsAg for more than 6 months prior to randomization
- •On entecavir or tenofovir treatment for at least 6 months prior to randomization and remaining on stable treatment during the study
- •Liver biopsy, fibroscan® or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic hepatitis B (HBV) infection without evidence of bridging fibrosis or cirrhosis
- •Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm during the study
- •Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least until the end of the follow-up period
排除标准
- •Healthy Participants' Exclusion Criteria:
- •Women who are lactating
- •Any suspicion or history of alcohol and/or other substance abuse or dependence in the past 6 months
- •Positive urine drug and alcohol screen (barbiturates, benzodiazepines, methadone, amphetamines, methamphetamines, opiates, cocaine, cannabinoids, and alcohol), or positive cotinine test at Day -1
- •Positive result on HBV, hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 and 2
- •A personal history of unexplained blackouts or faints, or known risk factors for Torsade de Pointes
- •Clinically significant abnormalities (as judged by the Investigator) in the physical examination and in the laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis) at screening and on Day -1
- •Participation in an investigational drug or device study within 90 days prior to screening or 5 times the half-life of the investigational drug (whichever is longer)
- •Donation of blood over 500 mL within three months prior to screening
- •Concomitant disease or condition (including allergic reactions against any drug, or multiple allergies) that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the healthy participant in this study
- •Chronic Hepatitis B-Infected Participants' Exclusion Criteria:
- •Women who are pregnant (positive pregnancy test) or lactating
- •History or other evidence of bleeding from esophageal varices
- •Decompensated liver disease
- •History or other evidence of a medical condition associated with chronic liver disease other than HBV infection
- •Documented history or other evidence of metabolic liver disease within one year of randomization
- •Positive test for hepatitis A (IgM anti-HAV), hepatitis C, or HIV
- •Documented history of infection with hepatitis D virus
- •Expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study, with the exception of oral therapy for herpes simplex virus (HSV) I or HSV II
- •History of immunologically-mediated disease
研究组 & 干预措施
Healthy Participants (Multiple-Ascending Dosing)
Experimental
干预措施: RO7020322 (Drug)
Participants with Chronic Hepatitis B (Proof of mechanism)
Experimental
干预措施: RO7020322 (Drug)
Healthy Participants (Multiple-Ascending Dosing)
Experimental
干预措施: Matching Placebo (Other)
Healthy Participants (Single-Ascending Dosing)
Experimental
干预措施: Matching Placebo (Other)
Healthy Participants (Single-Ascending Dosing)
Experimental
干预措施: RO7020322 (Drug)
Healthy Participants (Study of Food Effect)
Experimental
干预措施: Matching Placebo (Other)
Healthy Participants (Study of Food Effect)
Experimental
干预措施: RO7020322 (Drug)
Participants with Chronic Hepatitis B (Proof of mechanism)
Experimental
干预措施: Matching Placebo (Other)
结局指标
主要结局
Number of participants with adverse events
时间窗: Up to 8 weeks
Number of participants with clinically significant laboratory abnormalities
时间窗: Up to 8 weeks
Number of participants with clinically significant electrocardiogram (ECG) abnormalities
时间窗: Up to 8 weeks
Intensity of adverse events
时间窗: Up to 8 weeks
Number of participants with clinically significant vital signs abnormalities
时间窗: Up to 8 weeks
次要结局
- Area under the plasma concentration-time curve between time zero (pre-dose) extrapolated to infinity (AUC0-Inf) of RO7020322(Up to 18 days)
- Apparent clearance (CL/F) of RO7020322(Up to 18 days)
- Apparent volume (V/F) of RO7020322(Up to 18 days)
- Area under the plasma concentration-time curve (AUC0-t,ss) of RO7020322 at steady state(Up to 18 days)
- Apparent terminal phase half-life (t1/2) of RO7020322(Up to 18 days)
- Area under the plasma concentration-time curve (AUC0-t) of RO7020322 on Day 1(Up to 18 days)
- Plasma concentration of hepatitis B surface antigen (HBsAg)(Up to 8 weeks)
- Time from dosing to Cmax (Tmax) of RO7020322(Up to 18 days)
- Trough plasma concentrations (Ctrough) of RO7020322(Up to 18 days)
- Area under the plasma concentration-time curve between time zero (pre-dose) and the time of the last quantifiable concentration (AUClast) of RO7020322(Up to 18 days)
- Maximum observed plasma concentration (Cmax) of RO7020322(Up to 18 days)
研究者
研究点 (4)
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