Safety, Tolerability and Pharmacokinetics of Danoprevir/r in Healthy Volunteers China

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the Pharmacokinetics of Danoprevir in single dose (100mg QD on day 1, day 4 and day 14) and Ritonavir-boosted Danoprevir (100mg QD on day 4 and day 14) in single and multiple doses (100mg BID on day 5 -day 13) in healthy volunteers.

Official Title
-----------------
A Study on Safety, Tolerability and Pharmacokinetics of Ritonavir-boosted Danoprevir in Single and Multiple Doses in Healthy Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Danoprevir
* Drug: Ritonavir
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing and able to provide written informed consent Healthy men or women based on history, physical examination, laboratory examination and ECG. Negative serum or urine pregnancy test result (sensitivity of 25 mIU or better) for women with childbearing potential within the 24-hour period before the first dose of study drugs Female patients with childbearing potential (menopause within 1 year) must agree to use two reliable forms of effective non-hormonal contraception (i.e., condoms, cervical barriers, intrauterine device, spermicides, or sponge), at least 1 of which must be a physical barrier method, during treatment and for at least 6 months following the last dose of ribavirin All male patients with female partners of childbearing potential must use two reliable forms of effective contraception (combined) during treatment and for 6 months following the last dose of ribavirin Others as specified in the detailed protocol Exclusion Criteria: Have medical history, or has disease, such as cardiovascular system, respiratory system, endocrine and metabolic system, urinary system, digestive system, blood system, nerve system disease or psychiatric disease and acute or chronic infectious diseases and malignant tumors. Has a history of drug or food allergy. Positive hepatitis A antibody，positive hepatitis B surface antigen， positive hepatitis C antibody，syphilis antibody or HIV antibody at screening. Had gastrointestinal surgery, vagotomy, intestinal resection or any possible interference with gastrointestinal peristalsis, pH or absorbed by surgery. Pregnant, lactating or menstrual period and unwilling to reliable contraception period women of childbearing age. Female partners have fertility and reliable contraceptive measures of men.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PK Group (Danoprevir,Ritonavir)<br>Danoprevir(DNV)administered orally 100mg QD on day 1, day 4 and day 14;100mg BID on day 5 -day 13; Ritonavir administered orally 100mg QD on day 4 and day 14; 100mg BID on day 5 -day 13; | Drug: Danoprevir<br>* Danoprevir(DNV)administered orally 100mg QD on day 1, day 4 and day 14; 100mg BID on day 5 -day 13<br>* Other names: ASC08;Drug: Ritonavir<br>* Ritonavir administered orally 100mg QD on day 4 and day 14; 100mg BID on day 5 -day 13<br>* Other names: RTV;|
| Placebo Comparator: Placebo Group<br>ASC 08 Placebo administered orally 100mg QD on day 1, day 4 and day 14; 100mg BID on day 5 -day 13; Ritonavir administered orally 100mg QD on day 4 and day 14; 100mg BID on day 5 -day 13 for 14 days; | Drug: Ritonavir<br>* Ritonavir administered orally 100mg QD on day 4 and day 14; 100mg BID on day 5 -day 13<br>* Other names: RTV;Drug: Placebo<br>* ASC 08 Placebo administered orally 100mg QD on day 1, day 4 and day 14; 100mg BID on day 5 -day 13<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | 40 days | 
| Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max) |  | Up to 16 days | 
| Pharmacokinetics: Total area under the concentration-time curve form time 0 to 12 hours post-dose at steady-state |  | Up to 16 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pharmacokinetics,Danoprevir