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A Study of Darunavir in the Presence of Cobicistat When Administered as a Fixed Dose Combination Under Fed Conditions

Primary Purpose

Healthy

Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
Darunavir
Cobicistat
Darunavir/Cobicistat FDC
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Body mass index (BMI) between 18.5 and 30.0 kilograms per meter square (kg/m^2) inclusive, and body weight not less than 50.0 kg
  • Must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
  • Must be healthy on the basis of clinical laboratory tests performed at screening
  • Non-postmenopausal women must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta- hCG) 4 days or less before dosing of the first treatment period
  • A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of study drug
  • Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
  • Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
  • During the study and for a minimum of at least 90 days after receiving the last dose of study drug, a male participant: must wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak), must agree not to donate sperm for the purpose of reproduction

Exclusion Criteria:

  • Has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
  • Has received an investigational drug or used an investigational medical device within 60 days before the first administration of the study drug
  • Has a history of hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for hepatitis A antibody IgM, HBsAg or anti-HCV at screening
  • Has previously participated in more than 3 single-dose trials or a multiple-dose trial with darunavir (DRV) and/or cobicistat (COBI)
  • Has had any contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or Coronavirus Disease 2019 (COVID-19) patients within the last 2 weeks prior to admission to the clinical research center
  • Is a woman who is pregnant, breast-feeding, or planning to become pregnant during the study or within 90 days after the last dose of study drug, or a woman of childbearing potential who is unwilling to use acceptable methods of contraception
  • Has a history of human immunodeficiency virus type 1 or type 2 (HIV-1 or HIV-2) antibody positive, or tests positive for HIV at screening
  • Positive test for SARS-CoV-2 test participants within the last 2 weeks prior to admission or during the study
  • Is a man who plans to father a child while enrolled in the study or within 90 days after the last dose of study drug, or who is unwilling to use acceptable methods of contraception

Sites / Locations

  • SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Treatment A

Treatment B

Arm Description

Participants will receive Treatment A (a single dose of darunavir [DRV]/cobicistat [COBI] as one fixed dose combination [FDC] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence AB or BA). A washout period of at least 7 days will be maintained between each treatment period.

Participants will receive Treatment B (a single dose of DRV/COBI as separate tablets under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence BA or AB). A washout period of at least 7 days will be maintained between each treatment period.

Outcomes

Primary Outcome Measures

Maximum Observed Analyte Concentration (Cmax) of Darunavir (DRV)
Cmax is defined as the maximum observed analyte concentration of DRV.
Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of DRV
AUC(0-last) is the area under the analyte concentration-time curve from time zero to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.
Area Under the Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of DRV
AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) concentration, and lambda(z) is elimination rate constant.

Secondary Outcome Measures

Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Cmax of Cobicistat (COBI)
Cmax is defined as the maximum observed analyte concentration of COBI.
Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of COBI
AUC(0-last) is the area under the analyte concentration-time curve from time zero to the time of the last measurable (non-BQL) concentration, calculated by linear-linear trapezoidal summation.
Area Under the Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of COBI
AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) concentration, and lambda(z) is elimination rate constant.

Full Information

First Posted
January 20, 2021
Last Updated
July 18, 2022
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04718805
Brief Title
A Study of Darunavir in the Presence of Cobicistat When Administered as a Fixed Dose Combination Under Fed Conditions
Official Title
A Single-dose, Open-label, Randomized, Crossover Pivotal Bioequivalence Study in Healthy Participants to Assess the Bioequivalence of Darunavir 675 mg in the Presence of 150 mg Cobicistat When Administered as a Fixed Dose Combination (Darunavir/Cobicistat) Compared to the Co-administration of the Separate Agents (Darunavir and Cobicistat) Under Fed Conditions
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
January 26, 2021 (Actual)
Primary Completion Date
March 1, 2021 (Actual)
Study Completion Date
March 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the single-dose Pharmacokinetic (PK) and bioequivalence of darunavir (DRV) in the presence of cobicistat (COBI) when administered as a scored fixed dose combination (FDC) tablet (DRV/COBI) compared to the co-administration as the separate available tablet formulations (DRV and COBI), under fed conditions in healthy participants.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment A
Arm Type
Experimental
Arm Description
Participants will receive Treatment A (a single dose of darunavir [DRV]/cobicistat [COBI] as one fixed dose combination [FDC] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence AB or BA). A washout period of at least 7 days will be maintained between each treatment period.
Arm Title
Treatment B
Arm Type
Active Comparator
Arm Description
Participants will receive Treatment B (a single dose of DRV/COBI as separate tablets under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence BA or AB). A washout period of at least 7 days will be maintained between each treatment period.
Intervention Type
Drug
Intervention Name(s)
Darunavir
Other Intervention Name(s)
TMC114
Intervention Description
Participants will receive a single dose of Darunavir tablets orally as per assigned treatment sequence.
Intervention Type
Drug
Intervention Name(s)
Cobicistat
Other Intervention Name(s)
JNJ-48763364
Intervention Description
Participant will receive a single dose of Cobicistat tablets orally as per assigned treatment sequence.
Intervention Type
Drug
Intervention Name(s)
Darunavir/Cobicistat FDC
Intervention Description
Participants will receive a single dose of darunavir and cobicistat FDC tablets orally as per assigned treatment sequence.
Primary Outcome Measure Information:
Title
Maximum Observed Analyte Concentration (Cmax) of Darunavir (DRV)
Description
Cmax is defined as the maximum observed analyte concentration of DRV.
Time Frame
Predose, up to 72 hours post dose (up to Day 4)
Title
Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of DRV
Description
AUC(0-last) is the area under the analyte concentration-time curve from time zero to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.
Time Frame
Predose, up to 72 hours post dose (up to Day 4)
Title
Area Under the Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of DRV
Description
AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) concentration, and lambda(z) is elimination rate constant.
Time Frame
Predose, up to 72 hours post dose (up to Day 4)
Secondary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Description
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time Frame
Up to 6 weeks
Title
Cmax of Cobicistat (COBI)
Description
Cmax is defined as the maximum observed analyte concentration of COBI.
Time Frame
Predose, up to 72 hours post dose (up to Day 4)
Title
Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of COBI
Description
AUC(0-last) is the area under the analyte concentration-time curve from time zero to the time of the last measurable (non-BQL) concentration, calculated by linear-linear trapezoidal summation.
Time Frame
Predose, up to 72 hours post dose (up to Day 4)
Title
Area Under the Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of COBI
Description
AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) concentration, and lambda(z) is elimination rate constant.
Time Frame
Predose, up to 72 hours post dose (up to Day 4)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Body mass index (BMI) between 18.5 and 30.0 kilograms per meter square (kg/m^2) inclusive, and body weight not less than 50.0 kg Must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening Must be healthy on the basis of clinical laboratory tests performed at screening Non-postmenopausal women must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta- hCG) 4 days or less before dosing of the first treatment period A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 90 days after receiving the last dose of study drug Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol During the study and for a minimum of at least 90 days after receiving the last dose of study drug, a male participant: must wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak), must agree not to donate sperm for the purpose of reproduction Exclusion Criteria: Has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) Has received an investigational drug or used an investigational medical device within 60 days before the first administration of the study drug Has a history of hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for hepatitis A antibody IgM, HBsAg or anti-HCV at screening Has previously participated in more than 3 single-dose trials or a multiple-dose trial with darunavir (DRV) and/or cobicistat (COBI) Has had any contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or Coronavirus Disease 2019 (COVID-19) patients within the last 2 weeks prior to admission to the clinical research center Is a woman who is pregnant, breast-feeding, or planning to become pregnant during the study or within 90 days after the last dose of study drug, or a woman of childbearing potential who is unwilling to use acceptable methods of contraception Has a history of human immunodeficiency virus type 1 or type 2 (HIV-1 or HIV-2) antibody positive, or tests positive for HIV at screening Positive test for SARS-CoV-2 test participants within the last 2 weeks prior to admission or during the study Is a man who plans to father a child while enrolled in the study or within 90 days after the last dose of study drug, or who is unwilling to use acceptable methods of contraception
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
SGS Clinical Pharmacology Unit (located in ZNA Stuivenberg)
City
Antwerpen
ZIP/Postal Code
2060
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical- trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency

Learn more about this trial

A Study of Darunavir in the Presence of Cobicistat When Administered as a Fixed Dose Combination Under Fed Conditions

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