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

NCT04661397 | Completed Phase 1

• 3 other identifiers: CR1089222020-003396-18TMC114FD2HTX1007
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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 adult participants.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Analyte Concentration (Cmax) of Darunavir, 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, Emtricitabine and Tenofovir Alafenamide

  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.

  Up to 72 hours post-dose

Secondary Outcomes (4)

• Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide

  Up to 72 hours post-dose

• Cmax of Cobicistat

  Up to 72 hours post-dose

• AUC(0-last) of Cobicistat

  Up to 72 hours post-dose

• Number of Participants with Adverse Events (AEs)

  Up to 9 weeks

Study Arms (2)

Treatment A

EXPERIMENTAL

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; Drug: Darunavir; Drug: Emtricitabine/Tenofovir Alafenamide; Drug: Cobicistat

Treatment B

ACTIVE COMPARATOR

Participants will receive Treatment B (a single dose of Darunavir \[DRV\], Emtricitabine/Tenofovir Alafenamide \[F/TAF\] and Cobicistat \[COBI\] 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; Drug: Darunavir; Drug: Emtricitabine/Tenofovir Alafenamide; Drug: Cobicistat

Interventions

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC DRUG

Participants will receive a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC tablet orally as per assigned treatment sequence.

Also known as: TMC114/JNJ-48763364/JNJ-35807551/JNJ-63625328

Treatment A; Treatment B

Darunavir DRUG

Participants will receive a single dose of Darunavir orally as per assigned treatment sequence.

Treatment A; Treatment B

Emtricitabine/Tenofovir Alafenamide DRUG

Participants will receive a single dose of Emtricitabine/Tenofovir Alafenamide tablet orally as per assigned treatment sequence.

Treatment A; Treatment B

Cobicistat DRUG

Participant will receive a single dose of Cobicistat tablet orally as per assigned treatment sequence.

Treatment A; Treatment B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must have a body mass index (BMI = weight/height\^2) between 18.5 and 30.0 kilogram per meter square (kg/m\^2) (extremes included), and body weight not less than 50 kilogram (kg)
• Must be healthy on the basis of physical examination, medical history, vital signs, and electrocardiogram (ECG) performed at screening (results must be available on Day -1). 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 (results must be available on Day -1). 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. This determination must be recorded in the participant's source documents and initialed by the investigator
• 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
• 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

You may not qualify if:

• 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 ECG at screening or at admission to the study center as deemed appropriate by the investigator
• 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
• Has known allergies, hypersensitivity, or intolerance to Darunavir (DRV),Cobicistat (COBI), Emtricitabine (FTC), and/or Tenofovir Alafenamide (TAF), or any of their excipients
• Is a woman who is pregnant, or breast-feeding, or planning to become pregnant during this study or within 90 days after the last intake of study drug, or a woman of childbearing potential who is unwilling to use acceptable methods of contraception
• Has a history of hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen (HBsAg) or hepatitis C 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 a history of human immunodeficiency virus type 1 or type 2 (HIV-1 or HIV-2) infection, or tests positive for HIV-1 or HIV-2 at screening
• Has had any contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or coronavirus disease-19 (COVID-19) patients within the last 2 weeks prior to admission to the clinical research center

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini

Groningen, 9728 NZ, Netherlands

Location

Related Publications (1)

• Van Hemelryck S, Van Landuyt E, Ariyawansa J, Vanveggel S, Palmer M. Bioequivalence of a Pediatric Fixed-Dose Combination Tablet Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Compared With Coadministration of the Separate Agents in Healthy Adults: An Open-Label, Randomized, Replicate Crossover Study. Clin Pharmacol Drug Dev. 2023 Nov;12(11):1060-1068. doi: 10.1002/cpdd.1293. Epub 2023 Jun 19.

  PMID: 37335552 DERIVED

MeSH Terms

Interventions

Darunavir; emtricitabine tenofovir alafenamide; Cobicistat

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Study Officials

• Janssen Research & Development, LLC Clinical Trials

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 10, 2020
• Study Start: January 5, 2021
• Primary Completion: July 2, 2021
• Study Completion: July 2, 2021
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)