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

NCT04208061 | Completed Phase 1 FDA Drug

• 3 other identifiers: CR1086972019-003328-19TMC114FD1HTX1002
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability

  From signing of the ICF up to end of study (up to 8 weeks)

Study Arms (2)

Panel 1: Dabigatran etexilate +DRV/COBI

EXPERIMENTAL

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; Drug: DRV/COBI

Panel 2: Dabigatran etexilate +DRV+rtv

EXPERIMENTAL

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; Drug: Ritonavir; Drug: Darunavir

Interventions

Dabigatran Etexilate DRUG

Participants will receive single dose of dabigatran etexilate orally.

Panel 1: Dabigatran etexilate +DRV/COBI; Panel 2: Dabigatran etexilate +DRV+rtv

DRV/COBI DRUG

Participants will receive oral tablet of fixed dose combination (FDC) containing darunavir (DRV)/ cobicistat (COBI).

Also known as: REZOLSTA

Panel 1: Dabigatran etexilate +DRV/COBI

Ritonavir DRUG

Participants will receive ritonavir orally.

Panel 2: Dabigatran etexilate +DRV+rtv

Darunavir DRUG

Participants will receive Darunavir orally.

Panel 2: Dabigatran etexilate +DRV+rtv

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

Related Publications (2)

• LaRoche JK, Lanier J, Alvarenga R, Collins M, Costelloe T, Chiau A, Whetherly H, De Soete W, Faludi J, Rens K. Climate footprint of industry-sponsored in-human clinical trials: life cycle assessments of clinical trials spanning multiple phases and disease areas. BMJ Open. 2025 Feb 19;15(2):e085364. doi: 10.1136/bmjopen-2024-085364.

  PMID: 39971605 DERIVED

• LaRoche JK, Alvarenga R, Collins M, Costelloe T, De Soete W, Faludi J, Rens K. Climate footprint of industry-sponsored clinical research: an analysis of a phase-1 randomised clinical study and discussion of opportunities to reduce its impact. BMJ Open. 2024 Jan 11;14(1):e077129. doi: 10.1136/bmjopen-2023-077129.

  PMID: 38216192 DERIVED

MeSH Terms

Interventions

Dabigatran; Ritonavir; Darunavir

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Furans

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: December 23, 2019
• Study Start: December 18, 2019
• Primary Completion: March 25, 2021
• Study Completion: April 1, 2021
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)