A Bioequivalence Study of Darunavir, Emtricitabine, and Tenofovir Alafenamide, in the Presence of Cobicistat in Healthy Participants

Healthy Clinical Trial

Official title:

A Single-Dose, Open-Label, Randomized, Crossover Study to Assess the Bioequivalence of Darunavir 800 mg, Emtricitabine 200 mg, and Tenofovir Alafenamide 10 mg, in the Presence of Cobicistat 150 mg, Administered as Either a Fixed-Dose Combination Tablet or as Separate Agents in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02578550
• Other study ID #: CR107887
• Secondary ID: TMC114FD2HTX1001
• Status: Completed
• Phase: Phase 1
• First received: October 15, 2015
• Last updated: March 31, 2017
• Start date: November 2015
• Est. completion date: February 2016

Study information

• Verified date: March 2017
• Source: Janssen Sciences Ireland UC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the single-dose pharmacokinetics and pivotal bioequivalence of Darunavir (DRV) 800 milligram (mg), Emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg when administered as a fixed-dose combination (FDC) (D/C/F/TAF) relative to the separate agents (DRV 800 mg tablet formulation and FTC/TAF 200/10 mg FDC) in the presence of 150 mg Cobicistat (COBI), under fed conditions, in healthy participants.

Description:

This is a Phase 1, open-label, randomized, 2-way crossover study in 96 healthy adult participants. The study consists of 2 treatment sessions. Participants will receive in one session a single dose of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 milligram (mg) tablets as fixed-dose combination (FDC) and in another session Darunavir (DRV) as 1x 800 mg tablet, Emtricitabine/ tenofovir alafenamide (FTC/TAF) as 1x 200/10 mg FDC tablet, and Cobicistat (COBI) 150 mg as 1x 150 mg tablet all under fed conditions. Treatment sessions will be separated by a washout period of at least 7 days. The duration of the study for an individual participant will be at least 12 days, Screening and Follow-up not included. Participants safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participant must be non-smoker for at least 3 months prior to selection

• Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening. If the results are outside the normal reference ranges, the participant may be included only if they are not listed under the exclusion criteria and 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/signed by the Investigator

• Participant must have a body mass index (BMI), between 18.5 and 30 kilogram per square meter (kg/m^2) (inclusive)

• Participant must be healthy on the basis of clinical laboratory tests performed at Screening. If the results of the biochemistry panel, blood coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the abnormalities or deviations from normal are not listed in the exclusion criteria, and the Investigator judges they are not clinically significant. This determination must be recorded in the participant's source documents and initialed/signed by the Investigator

• All female participants, except when postmenopausal, must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at Screening and must not breastfeed from Screening onwards

Exclusion Criteria:

• Participant has a positive human immunodeficiency virus - type (HIV-1) or human immunodeficiency virus - type 2 (HIV-2) test at Screening

• Participant has hepatitis A, B, or C infection (confirmed by a positive hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen, and/or hepatitis C virus antibody, respectively) at Screening

• Participant has currently significant and active gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, endocrinologic, genitourinary, renal, hepatic, respiratory, inflammatory, neoplastic, or infectious disease. Currently active dermatological disease that would interfere with a correct assessment of possible skin reactions to the study drugs

• Participant has currently significant and active diarrhea, nausea, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability

• Participant has any history of renal insufficiency

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC)
A single tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg will be administered.
• Emtricitabine/tenofovir alafenamide FDC
A single tablet containing FTC 200 mg and TAF 10 mg will be administered.
• Darunavir
A single tablet containing darunavir 800 mg will be administered.
• Cobicistat
A single table containing cobistat 150 mg will be administered.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Sciences Ireland UC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide	The Cmax is the maximum observed plasma concentration.	Up to 72 hours post-dose
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Up to 72 hours post-dose
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.	Up to 72 hours post-dose
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.	Up to 72 hours post-dose
Secondary	Plasma Concentration at the Last Quantifiable Time Point (Clast) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	The Clast is the last observed quantifiable plasma concentration above the quantification limit.	Up to 72 hours post-dose
Secondary	Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	Lambda(z) is firstorder elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log linear phase of the drug concentrationtime curve.	Up to 72 hours post-dose
Secondary	Elimination HalfLife (t1/2) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	The elimination halflife (t1/2) is the time needed for the plasma concentration to decrease to 1 half of its original value. It is associated with the terminal slope of the semi logarithmic drug concentrationtime curve, and is calculated as 0.693/lambda(z).	Up to 72 hours post-dose
Secondary	Time to Last Quantifiable Plasma Concentration (Tlast) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	The Tlast is the time to last observed quantifiable plasma concentration.	Up to 72 hours post-dose
Secondary	Ratio of AUClast of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	Ratio of individual AUClast values between Treatment A and B.	Up to 72 hours post-dose
Secondary	Ratio of AUC[0infinity] of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	Ratio of individual AUC[0infinity] values between Treatment A and B.	Up to 72 hours post-dose
Secondary	Ratio of Cmax of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)	Ratio of individual Cmax values between Treatment A and B.	Up to 72 hours post-dose
Secondary	Number of Subjects 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 the Informed Consent Form (ICF) up to 10 days after last study drug administration