PF-07321332/Ritonavir and Ritonavir on Dabigatran Study in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
This is a drug-drug interaction study to assess the effects of PF-07321332/ritonavir and ritonavir on the Pharmacokinetic (PK) of dabigatran in healthy volunteers. PK will be evaluated for PF-07321332 and ritonavir. Dabigatran is being utilized as a P-gp substrate

Official Title
-----------------
A PHASE 1, OPEN-LABEL, 3-TREATMENT, 6-SEQUENCE, 3-PERIOD CROSSOVER STUDY TO ESTIMATE THE EFFECT OF PF-07321332/RITONAVIR AND RITONAVIR ON THE PHARMACOKINETICS OF DABIGATRAN IN HEALTHY PARTICIPANTS

Conditions
-----------------
Healthy Participants

Intervention / Treatment
-----------------
* Drug: Dabigatran
* Drug: PF-07321332/ritonavir + Dabigatran
* Drug: Ritonavir + Dabigatran


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body Mass Index (BMI) of 17.5 to 30.5 kg.m2; and a total body weight >50 kg (110 lbs) Female participants must have a negative pregnancy test Exclusion Criteria: Positive test for SARS-Co-V2 at the time of screening or Day -1 Active pathological bleeding or risk of bleeding Positive urine drug test History of sensitivity to heparin or heparin induced thrombocytopenia Participants who have been vaccinated for COVID-19 in the past 7 days

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a Phase1, open-label,3-treatment, 6-sequence, 3-period crossover study to estimate the effect of PF-07321332/ritonavir and ritonavir on the Pharmacokinetics of dabigatran in healthy participants
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment A<br>Dabigatran only | Drug: Dabigatran<br>* A single dose of Dabigatran on Day 1<br>|
| Experimental: Treatment B<br>PF-07321332/ritonavir + Dabigatran | Drug: PF-07321332/ritonavir + Dabigatran<br>* PF-07321332/ritonavir twice daily (BID) for Days 1 and 2 Single dose of Dabigatran on Day 2<br>|
| Active Comparator: Treatment C<br>Ritonavir + Dabigatran | Drug: Ritonavir + Dabigatran<br>* Ritonavir BID on Days 1 and 2 Single dose of Dabigatran on Day 2<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve from time zero to infinity (AUCinf) of dabigatran when administer with PF-07321332/ritonavir |  | Treatment A; pre-dose, and 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of dabigatran when administered with PF-07321332/ritonavir |  | Treatment A; pre-dose, and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf of dabigatran when administered with multiple doses of ritonavir |  | Treatment C; Pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post-dose | 
| Cmax of dabigatran when administered with multiple doses of ritonavir |  | Treatment C; pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |  | Treatments A, B and C; through study completion of approximately 1.5 months | 
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities |  | Treatments A, B, and C; through study completion of approximately 1.5 months | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs |  | Treatment A, B, and C; through study completion of approximately 1.5 months | 
| Number of Participants With Abnormalities in Physical Examination |  | Treatment A, B, and C; through study completion of approximately 1.5 months | 
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings |  | Treatment A, B, and C; through study completion of approximately 1.5 months | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of dabigatran |  | Treatments A, B and C; Pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours | 
| Plasma Decay Half-Life (t1/2) of dabigatran |  | Treatments A, B and C; pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 
| Cmax of PF-07321332 |  | Treatments A, B, C: pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 
| AUCtau (area under the curve of the dosing interval) of PF-0321332 |  | Treatments A, B and C: pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 
| Tmax of PF-0321332 |  | Treatments A, B and C: pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 
| T1/2 of PF-0321332 |  | Treatments A, B and C: pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 
| Apparent Oral Clearance (CL/F) of PF-0321332 |  | Treatments A, B and C: pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 
| Apparent Volume of Distribution (Vz/F) of PF-0321332 |  | Treatments A, B and C: pre-dose and 1, 2, 4, 6, 8, 12, 16, 24, and 48 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Drug Interaction, Dabigatran, P-gp Substrate, SARS-Co-V2, COVID-19, protease inhibitor, ritonavir