A Study of Darunavir in Combination With Cobicistat or Ritonavir, and Dabigatran Etexilate in Healthy Participants

A Phase 1, 2-Panel, Fixed-Sequence, Open-Label Single-Center Study to Assess the Effect of Single and Multiple Doses of Darunavir in Combination With Cobicistat or Ritonavir on the Pharmacokinetics of Single Dose Dabigatran Etexilate in Healthy Subjects

The purpose of this study is to evaluate effect of single and repeated doses of darunavir (DRV) in combination with cobicistat (DRV/COBI) and with ritonavir (DRV+rtv) on the pharmacokinetics of single dose dabigatran etexilate (measured in plasma as free and total dabigatran) when co-administered in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dabigatran Etexilate; Drug: DRV/COBI; Drug: Ritonavir; Drug: Darunavir

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must have a body mass index (BMI) (weight in kilogram [kg]/height^2 in square meters [m^2] ) between 18.0 and 30.0 kg/m^2 (inclusive) and body weight not less than 50.0 kg
• Must sign an informed consent form (ICF) indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study
• A woman must have a negative highly sensitive serum beta human chorionic gonadotropin (beta hCG) pregnancy test at screening, on Day -1 (only if the test performed at screening was greater than [>] 4 days before dosing), and at the end of the study
• 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
• Must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
• A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last dose of study drug

Exclusion Criteria:

• Clinically significant abnormalities during physical examination, vital signs, or 12 lead - electrocardiogram (ECG) at screening 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
• With a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs
• Has donated blood or blood products or had substantial loss of blood (more than 500 milliliter [mL]) within 3 months before the first administration of study drug or intention to donate blood or blood products during the study
• Has received an investigational drug or used an investigational medical device within 60 days before the first intake of study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Panel 1: Dabigatran etexilate +DRV/COBI; Participants will receive Treatment A (single dose of Dabigatran etexilate orally) on Day 1 followed by Treatment B (single dose of Darunavir/ cobicistat [DRV/COBI] as fixed dose combination tablet orally and single dose of dabigatran etexilate) on Day 4 followed by Treatment C ([DRV/COBI] as fixed dose combination tablet orally once daily from Day 5 to Day 20 and single dose of dabigatran etexilate on Day 18).	Drug: Dabigatran Etexilate; Participants will receive single dose of dabigatran etexilate orally.; Drug: DRV/COBI; Participants will receive oral tablet of fixed dose combination (FDC) containing darunavir (DRV)/ cobicistat (COBI).; Other Names: REZOLSTA
EXPERIMENTAL: Panel 2: Dabigatran etexilate +DRV+rtv; Participants will receive Treatment D (single dose of dabigatran etexilate orally) on Day 1 followed by Treatment E (single doses of Darunavir, and ritonavir [rtv], and single dose of dabigatran etexilate on Day 4), followed by Treatment F (DRV and rtv orally once daily from Day 5 to Day 20 and single dose of dabigatran etexilate on Day 18).	Drug: Dabigatran Etexilate; Participants will receive single dose of dabigatran etexilate orally.; Drug: Ritonavir; Participants will receive ritonavir orally.; Drug: Darunavir; Participants will receive Darunavir orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Analyte Concentration (Cmax) of Dabigatran Etexilate (Free and Total)	Cmax is the maximum observed analyte concentration.	Up to Day 18
Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Dabigatran Etexilate (Free and Total)	AUC(0-last) is the Area under the curve (AUC) from time 0 to the time of last measurable (non-below quantification limit) concentration, calculated by linear-linear trapezoidal summation.	Up to Day 18
Area Under the Plasma Concentration-Time Curve from Time Zero to Infinite Time (AUC0-infinity) of Dabigatran Etexilate (Free and Total)	AUC(0-infinity) is defined as area under the plasma concentration-time curve from time zero to infinite time.	Up to Day 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	From signing of the ICF up to end of study (up to 8 weeks)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2019
• Primary Completion (ACTUAL): March 25, 2021
• Study Completion (ACTUAL): April 1, 2021

Study Registration Dates

• First Submitted: December 19, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (ACTUAL): December 23, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; HIV Protease Inhibitors; Viral Protease Inhibitors; Dabigatran; Ritonavir; Darunavir
• Other Study ID Numbers: CR108697; 2019-003328-19 (EUDRACT_NUMBER); TMC114FD1HTX1002 (OTHER: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes