A Phase 4 Study to Evaluate Pharmacokinetics and Safety of Darunavir Along With Ritonavir in Healthy Male Japanese Participants

A Study to Evaluate the Pharmacokinetics and Safety of Oral Single-Dose JNS011 Tablet in Combination With Low-Dose Ritonavir Capsule in Healthy Japanese Adult Males

The purpose of this study is to evaluate the pharmacokinetics (explores what the body does to the drug) and safety of darunavir, and will be administered in combination with Ritonavir in healthy adult Japanese male participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Darunavir; Drug: Ritonavir

Detailed Description

This is an open-label (all people know the identity of the intervention), single oral-dose and post-marketing study of darunavir administered in combination with low-dose ritonavir in healthy adult Japanese male participants. The total study duration will be approximately of 14 days per participant. The study consists of 3 parts: Screening (that is, 28 days before study commences on Day 1); Treatment (that is, Day 1-5); and Follow-up (that is, up to Day 13). The participants will be hospitalized for 6 nights and 7 days. All the eligible participants will receive Darunavir oral tablet on Day 3 and ritonavir capsule orally twice daily from Day 1-5. Participants will keep upright position until 4 hours after study drug administration. Both the drugs will be administered within 15 minutes after completion of meal. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tsukuba, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male Participants provided with sufficient explanation of the investigational product, the drugs to be provided and this clinical study prior to the start of participation in the clinical study, and capable of providing voluntary informed consent in writing
• Male Participants with a Body Mass Index (BMI) between 18.5 and 25.0 kilogram per square meter (kg/m^2) at the time of the Screening tests
• Non-smokers or male participants who are capable of abstaining from smoking during the period from the day before the Screening tests until the completion of the post-treatment examinations
• Male Participants consenting to use a medically-approved contraceptive method (such as condoms or the like) during the period from hospital admission until the completion of the post-treatment examinations
• Male Participants showing no clinically significant abnormalities at the time of Screening, on the day prior

Exclusion Criteria:

• Participants suffering or with a history of diseases related to the liver, kidneys, circulatory system, respiratory system, digestive system, neuropsychiatric system, hematopoietic function or endocrine function and who may be inappropriate for participation in this clinical study
• Participants who participated in another clinical study and were treated with another investigational product within 120 days prior to the start of the initial dosing of the provided drugs
• Participants giving 200 milliliter (mL) or more of blood within 30 days prior to the start of the initial dosing of the provided drugs or giving 400 mL or more of blood within 90 days prior to the start of the initial dosing of the provided drugs (such as blood donation), or giving a total of 1200 mL or more of blood within the past year
• Participants with a history of hypersensitivity to sulfonamide drugs, drug allergies or drug hypersensitivity, alcohol, pharmaceutical or drug addiction, or who may be addicted
• Participants with positive results for Human Immunodeficiency Virus antigen or antibodies, Hepatitis C Virus antibodies, Hepatitis B Surface antigen or the serological test for syphilis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ritonavir and darunavir; Ritonavir will be administered orally twice daily at a dose of 100 milligram (mg) from Day 1-5. Darunavir ethanolate will be administered as single oral dosing of two tablets of 300 mg on Day 3.	Drug: Darunavir; Darunavir ethanolate will be administered as single oral dosing of two tablets of 300 milligram (mg) on Day 3.; Other Names: JNS011; Drug: Ritonavir; Ritonavir capsule will be administered orally twice daily at a dose of 100 mg for 5 days.; Other Names: Ritonavir will be administered orally twice daily as 100 mg capsule from Day 1-5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma Darunavir Concentration	Plasma concentration of Darunavir will be determined by collecting blood samples at the defined time points.	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3
Maximum Plasma Concentration (Cmax) of Darunavir	The Cmax is the maximum plasma concentration.	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Darunavir	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3
Terminal Half-Life(t[1/2]) of Darunavir	Terminal half-life (t[(1/2]) is defined as 0.693/Lambda(z).	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3
Time to reach maximum concentration (tmax) of Darunavir	The Tmax is time to reach the maximum plasma concentration.	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) of Darunavir	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3
Apparent total body clearance (CL/F) of Darunavir	Clearance is a quantitative measure of the rate at which a drug substance is removed from the body. The CL/F will be calculated by dividing the dose by AUC (0-infinity)	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3
Apparent volume of distribution at the terminal Phase (Vd[z] /F) of Darunavir	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.The Vd(z)/F will be calculated by dividing CL/F by lambda(z).	0 hour (pre-dose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 24, 48 and 72 hours post-dose of darunavir on Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma Ritonavir Concentration	Plasma concentration of Darunavir will be determined by collecting blood samples at the defined time points.	0 hour (pre-dose) on Day 1, 2, 3, 4 and 5
Maximum Plasma Concentration (Cmax) of Ritonavir	The Cmax is the maximum plasma concentration.	0 hour (pre-dose) on Day 1, 2, 3, 4 and 5
Time to reach maximum concentration (tmax) of Ritonavir	The Tmax is time to reach the maximum plasma concentration.	0 hour (pre-dose) on Day 1, 2, 3, 4 and 5
Area Under the Plasma Concentration-Time Curve From Time Zero to 12 hours (AUC [0-12]) of Ritonavir	The AUC (0-12) is the area under the plasma concentration-time curve from time zero to 12 hours, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	0 hour (pre-dose) on Day 1, 2, 3, 4 and 5

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 12, 2013
• First Submitted That Met QC Criteria: March 12, 2013
• First Posted (Estimate): March 14, 2013

Study Record Updates

• Last Update Posted (Estimate): April 10, 2013
• Last Update Submitted That Met QC Criteria: April 9, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Healthy; Ritonavir; Darunavir; JNS011
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Darunavir
• Other Study ID Numbers: CR100323; JNS011-JPN-01