HealthyPhase 1NCT04236453

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 Phase 1 study testing Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC, Darunavir and Emtricitabine/Tenofovir Alafenamide in people with Healthy, run by Janssen Pharmaceutica N.V., Belgium at 1 site in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC, Darunavir and Emtricitabine/Tenofovir Alafenamide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteNetherlands
Study dates: 23 Jan 2020to 10 Apr 2020
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

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

Other trials in Netherlands

About this study

Official title: 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.

Conditions: Healthy
Being tested: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC, Darunavir, Emtricitabine/Tenofovir Alafenamide, Cobicistat

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDCDrug
Also called TMC114/JNJ-48763364/JNJ-35807551/JNJ-63625328
Participants will receive a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC tablet orally on Day 1 of treatment periods with Treatment A.
DarunavirDrug
Participants will receive a single dose of Darunavir orally on Day 1 of treatment periods with Treatment B.
Emtricitabine/Tenofovir AlafenamideDrug
Participants will receive a single dose of Emtricitabine/Tenofovir Alafenamide tablet orally on Day 1.
CobicistatDrug
Participant will receive a single dose of Cobicistat tablet orally on Day 1.

Study groups in NCT04236453
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC; Drug: Darunavir; Drug: Emtricitabine/Tenofovir Alafenamide; Drug: Cobicistat

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Analyte Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Cmax is the maximum observed analyte concentration.
Measured: 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.
Measured: 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
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.
Measured: Up to 72 hours post-dose
Cmax of Cobicistat
Cmax is the maximum observed analyte concentration of Cobicistat.
Measured: 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.
Measured: 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.
Measured: From signing of the Informed consent form (ICF) till the last study-related activity (up to 10 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jan 202010 Apr 2020

First posted22 Jan 2020
Study start23 Jan 2020
Primary completion10 Apr 2020
Study completion10 Apr 2020

Why it stopped: COVID-19 pandemic impacted the BE assessment of the trial. The clinical team decided to terminate the trial in order to start a new pivotal BE trial

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HealthyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04236453
Sponsor's protocol ID: CR108649
Other IDs: 2019-002245-37, TMC114FD2HTX1005, 2019
Status last verified: Jul 2020
First submitted: 21 Jan 2020
Last updated: 7 Jul 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04236453
Acronym / sponsor ID: CR108649
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: COVID-19 pandemic impacted the BE assessment of the trial. The clinical team decided to terminate the trial in order to start a new pivotal BE trial
Enrolment: 16 participants (actual)
Lead sponsor: Janssen Pharmaceutica N.V., BelgiumIndustry (pharma, biotech, devices)
Study start: 23 Jan 2020 (actual)
Primary completion: 10 Apr 2020 (actual)
Study completion: 10 Apr 2020 (actual)
First posted: 22 Jan 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment A	Experimental	Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC, Drug: Darunavir, Drug: Emtricitabine/Tenofovir Alafenamide, Drug: CobicistatParticipants 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.
Treatment B	Active comparator	Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC, Drug: Darunavir, Drug: Emtricitabine/Tenofovir Alafenamide, Drug: CobicistatParticipants 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.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDCAlso: TMC114/JNJ-48763364/JNJ-35807551/JNJ-63625328Participants will receive a single dose of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC tablet orally on Day 1 of treatment periods with Treatment A.	Drug	Treatment A, Treatment B
DarunavirParticipants will receive a single dose of Darunavir orally on Day 1 of treatment periods with Treatment B.	Drug	Treatment A, Treatment B
Emtricitabine/Tenofovir AlafenamideParticipants will receive a single dose of Emtricitabine/Tenofovir Alafenamide tablet orally on Day 1.	Drug	Treatment A, Treatment B
CobicistatParticipant will receive a single dose of Cobicistat tablet orally on Day 1.	Drug	Treatment A, Treatment B

Primary outcome

Maximum Observed Analyte Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Time frame: Up to 72 hours post-dose
Cmax is the maximum observed analyte concentration.
Area Under the Analyte Concentration-time Curve from time Zero to Last Quantifiable time (AUC[0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Time frame: Up to 72 hours post-dose
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.

4 secondary outcomes

Area Under the Analyte Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide
Time frame: Up to 72 hours post-dose
Cmax of Cobicistat
Time frame: Up to 72 hours post-dose
AUC(0-last) of Cobicistat
Time frame: Up to 72 hours post-dose
Number of Participants with Adverse Events
Time frame: From signing of the Informed consent form (ICF) till the last study-related activity (up to 10 weeks)

Results and safety

The study was stopped early (reason given: COVID-19 pandemic impacted the BE assessment of the trial. The clinical team decided to terminate the trial in order to start a new pivotal BE trial). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2020.
Individual participant dataSharing planned: Yes. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Janssen Pharmaceutica N.V., Belgium Clinical Trials study director

Janssen Pharmaceutica N.V., Belgium

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Analyte Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide (time frame: Up to 72 hours post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04236453.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2020.