A Study in Healthy Participants to Assess the Effect of Darunavir, Emtricitabine, and Tenofovir Alafenamide in the Presence of Cobicistat When Administered as a Fixed Dose Combination (Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide) Compared to the Co-administration of the Separate Agents

A Single-Dose, Open-Label, Randomized, Replicate Crossover Pivotal Bioequivalence Study in Healthy Subjects to Assess the Bioequivalence of Darunavir 675 mg, Emtricitabine 200 mg, and Tenofovir Alafenamide 10 mg in the Presence of Cobicistat 150 mg When Administered as a Fixed Dose Combination (Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide) Compared to the Co-administration of the Separate Agents (Darunavir, Cobicistat, and Emtricitabine/Tenofovir Alafenamide), Under Fed Conditions

The purpose of the study is to evaluate the single-dose pharmacokinetics (PK) and pivotal bioequivalence of 3 compounds Darunavir (DRV), emtricitabine (FTC), and tenofovir alafenamide (TAF) in the presence of cobicistat (COBI) when administered as an fixed dose combination (FDC) (Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide [D/C/F/TAF]) compared to the co-administration as the separate commercial formulations (DRV and F/TAF and COBI), under fed conditions, in healthy participants.

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC; Drug: Darunavir; Drug: Emtricitabine/Tenofovir Alafenamide; Drug: Cobicistat

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be healthy on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG) performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
• Participant must be healthy on the basis of clinical laboratory test performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant.
• A woman (of childbearing potential) must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test, 4 days or less before dosing of the first treatment period
• Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
• 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
• 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 subject 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.
• Must be willing and able to adhere to the prohibitions and restrictions specified in the study protocol

Exclusion Criteria:

• Has history or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease (including bronchospastic respiratory disease), diabetes mellitus, hepatic or renal insufficiency (for example, estimated creatinine clearance below less than [<] 90 milliliter per minute [mL/min] at screening), gastrointestinal disease (such as significant diarrhea, gastric stasis, or constipation that in the investigator's opinion could influence drug absorption or bioavailability), thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• Had one or more of the laboratory abnormalities at screening as outlined in the protocol by the Division of Acquired immunodeficiency syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events and in accordance with the normal ranges of the clinical laboratory
• Clinically significant abnormalities during physical examination, vital signs, or 12 lead electrocardiogram (ECG) at screening or at admission to the study center as deemed appropriate by the investigator
• With any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
• Has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before screening or positive test result(s) for alcohol and/or drugs of abuse (such as hallucinogens, barbiturates, opiates, opioids, cocaine, cannabinoids, amphetamines, methadone, benzodiazepines, methamphetamine, tetrahydrocannabinol, phencyclidine, and tricyclic antidepressants) either at screening or on Day 1 of each treatment period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Participants will receive Treatment A (a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide [D/C/F/TAF] as one fixed dose combination [FDC] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A wash out period of at least 7 days will be maintained between each treatment period.	Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC; Participants will receive a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC tablet orally on Day 1 of treatment periods with Treatment A.; Other Names: TMC114/JNJ-48763364/JNJ-35807551/JNJ-63625328; Drug: Darunavir; Participants will receive a single dose of Darunavir orally on Day 1 of treatment periods with Treatment B.; Drug: Emtricitabine/Tenofovir Alafenamide; Participants will receive a single dose of Emtricitabine/Tenofovir Alafenamide tablet orally on Day 1.; Drug: Cobicistat; Participant will receive a single dose of Cobicistat tablet orally on Day 1.
Active Comparator: Treatment B; Participants will receive Treatment B (a single dose of Darunavir [DRV], Emtricitabine/Tenofovir Alafenamide [F/TAF] and Cobicistat [COB] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence ABBA or BAAB). A washout period of at least 7 days will be maintained between each treatment period.	Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC; Participants will receive a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC tablet orally on Day 1 of treatment periods with Treatment A.; Other Names: TMC114/JNJ-48763364/JNJ-35807551/JNJ-63625328; Drug: Darunavir; Participants will receive a single dose of Darunavir orally on Day 1 of treatment periods with Treatment B.; Drug: Emtricitabine/Tenofovir Alafenamide; Participants will receive a single dose of Emtricitabine/Tenofovir Alafenamide tablet orally on Day 1.; Drug: Cobicistat; Participant will receive a single dose of Cobicistat tablet orally on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Analyte Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide	Cmax is the maximum observed analyte concentration.	Up to 72 hours post-dose
Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide	AUC(0-last) is the area under the analyte concentration-time curve of from time 0 to the time of the last measurable (non-below quantification limit [non-BQL]) concentration, calculated by linear-linear trapezoidal summation.	Up to 72 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide	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, C(last) is the last observed measurable concentration, and lambda(z) is elimination rate constant.	Up to 72 hours post-dose
Cmax of Cobicistat	Cmax is the maximum observed analyte concentration of Cobicistat.	Up to 72 hours post-dose
AUC(0-last) of Cobicistat	AUC(0-last) is the area under the analyte concentration-time curve of from time 0 to the time of the last measurable (non-BQL) concentration, calculated by linear-linear trapezoidal summation.	Up to 72 hours post-dose
Number of Participants with Adverse Events	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	From signing of the Informed consent form (ICF) till the last study-related activity (up to 10 weeks)

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutica N.V., Belgium
• Investigators: Study Director: Janssen Pharmaceutica N.V., Belgium Clinical Trials, Janssen Pharmaceutica N.V., Belgium

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Actual): April 10, 2020
• Study Completion (Actual): April 10, 2020

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 21, 2020
• First Posted (Actual): January 22, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 3, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; 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; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Cobicistat; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Darunavir; Cobicistat mixture with darunavir
• Other Study ID Numbers: CR108649; 2019-002245-37 (EudraCT Number); TMC114FD2HTX1005 (Other Identifier: Janssen Pharmaceutica N.V., Belgium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No