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

NCT04236453 | Terminated Phase 1

• 3 other identifiers: CR1086492019-002245-37TMC114FD2HTX1005
• Study Type: interventional
• Target: 16
• 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 participants.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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 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

  From signing of the Informed consent form (ICF) till the last study-related activity (up to 10 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 \[COB\] 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; 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 on Day 1 of treatment periods with Treatment A.

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 on Day 1 of treatment periods with Treatment B.

Treatment A; Treatment B

Emtricitabine/Tenofovir Alafenamide DRUG

Participants will receive a single dose of Emtricitabine/Tenofovir Alafenamide tablet orally on Day 1.

Treatment A; Treatment B

Cobicistat DRUG

Participant will receive a single dose of Cobicistat tablet orally on Day 1.

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 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

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 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

Sponsors & Collaborators

• Janssen Pharmaceutica N.V., Belgium: lead

Study Sites (1)

PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini

Groningen, 9728 NZ, Netherlands

Location

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 Pharmaceutica N.V., Belgium Clinical Trials

  Janssen Pharmaceutica N.V., Belgium

  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: January 21, 2020
• First Posted: January 22, 2020
• Study Start: January 23, 2020
• Primary Completion: April 10, 2020
• Study Completion: April 10, 2020
• Last Updated: July 7, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)