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

NCT ID: NCT04661397

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-05
• Study Completion Date: 2021-07-02

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC

Intervention Type: DRUG

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

Darunavir

Intervention Type: DRUG

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

Emtricitabine/Tenofovir Alafenamide

Intervention Type: DRUG

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

Cobicistat

Intervention Type: DRUG

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

Treatment B

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.

Group Type: ACTIVE_COMPARATOR

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC

Intervention Type: DRUG

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

Darunavir

Intervention Type: DRUG

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

Emtricitabine/Tenofovir Alafenamide

Intervention Type: DRUG

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

Cobicistat

Intervention Type: DRUG

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

Interventions

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC

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

Intervention Type: DRUG

Darunavir

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

Intervention Type: DRUG

Emtricitabine/Tenofovir Alafenamide

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

Intervention Type: DRUG

Cobicistat

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

Intervention Type: DRUG

Other Intervention Names

TMC114/JNJ-48763364/JNJ-35807551/JNJ-63625328

Eligibility Criteria

Inclusion Criteria

• 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

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 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trials

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini

Groningen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 37335552 (View on PubMed)

Other Identifiers

2020-003396-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TMC114FD2HTX1007

Identifier Type: OTHER

Identifier Source: secondary_id

CR108922

Identifier Type: -

Identifier Source: org_study_id