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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran Etexilate
* Drug: DRV/COBI
* Drug: Ritonavir
* Drug: Darunavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel 1: Dabigatran etexilate +DRV/COBI<br>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<br>* Participants will receive single dose of dabigatran etexilate orally.<br>Drug: DRV/COBI<br>* Participants will receive oral tablet of fixed dose combination (FDC) containing darunavir (DRV)/ cobicistat (COBI).<br>* Other names: REZOLSTA;|
| Experimental: Panel 2: Dabigatran etexilate +DRV+rtv<br>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<br>* Participants will receive single dose of dabigatran etexilate orally.<br>Drug: Ritonavir<br>* Participants will receive ritonavir orally.<br>Drug: Darunavir<br>* Participants will receive Darunavir orally.<br>|

What is the study measuring?
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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) |