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

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ClinicalTrials.gov Identifier: NCT01810887
Recruitment Status : Completed
First Posted : March 14, 2013
Last Update Posted : April 10, 2013
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Darunavir Drug: Ritonavir Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2008
Actual Primary Completion Date : July 2008
Actual Study Completion Date : July 2008

Resource links provided by the National Library of Medicine


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 Name: JNS011

Drug: Ritonavir
Ritonavir capsule will be administered orally twice daily at a dose of 100 mg for 5 days.
Other Name: Ritonavir will be administered orally twice daily as 100 mg capsule from Day 1-5.




Primary Outcome Measures :
  1. Change in Plasma Darunavir Concentration [ Time Frame: 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 ]
    Plasma concentration of Darunavir will be determined by collecting blood samples at the defined time points.

  2. Maximum Plasma Concentration (Cmax) of Darunavir [ Time Frame: 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 ]
    The Cmax is the maximum plasma concentration.

  3. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Darunavir [ Time Frame: 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 ]
    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.

  4. Terminal Half-Life(t[1/2]) of Darunavir [ Time Frame: 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]) is defined as 0.693/Lambda(z).

  5. Time to reach maximum concentration (tmax) of Darunavir [ Time Frame: 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 ]
    The Tmax is time to reach the maximum plasma concentration.

  6. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last]) of Darunavir [ Time Frame: 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 ]
    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.

  7. Apparent total body clearance (CL/F) of Darunavir [ Time Frame: 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 ]
    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)

  8. Apparent volume of distribution at the terminal Phase (Vd[z] /F) of Darunavir [ Time Frame: 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 ]
    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).


Secondary Outcome Measures :
  1. Change in Plasma Ritonavir Concentration [ Time Frame: 0 hour (pre-dose) on Day 1, 2, 3, 4 and 5 ]
    Plasma concentration of Darunavir will be determined by collecting blood samples at the defined time points.

  2. Maximum Plasma Concentration (Cmax) of Ritonavir [ Time Frame: 0 hour (pre-dose) on Day 1, 2, 3, 4 and 5 ]
    The Cmax is the maximum plasma concentration.

  3. Time to reach maximum concentration (tmax) of Ritonavir [ Time Frame: 0 hour (pre-dose) on Day 1, 2, 3, 4 and 5 ]
    The Tmax is time to reach the maximum plasma concentration.

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to 12 hours (AUC [0-12]) of Ritonavir [ Time Frame: 0 hour (pre-dose) on Day 1, 2, 3, 4 and 5 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01810887


Locations
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Japan
Tsukuba, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
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Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.

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Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01810887     History of Changes
Other Study ID Numbers: CR100323
JNS011-JPN-01
First Posted: March 14, 2013    Key Record Dates
Last Update Posted: April 10, 2013
Last Verified: April 2013
Keywords provided by Janssen Pharmaceutical K.K.:
Healthy
Darunavir
JNS011
Ritonavir
Additional relevant MeSH terms:
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Ritonavir
Darunavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors