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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Dabigatran; Drug: PF-07321332/ritonavir + Dabigatran; Drug: Ritonavir + Dabigatran

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Centers of America ( Hollywood )

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Maximum Plasma Concentration (Cmax)	Cmax was defined as maximum observed plasma concentration.	Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUCinf	AUCinf was defined as the area under the plasma concentration-time curve from time 0 extrapolated to infinity	Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUClast	AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.	Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Maximum Plasma Concentration (Cmax)	Cmax was defined as maximum observed plasma concentration	Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinf	AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity	Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClast	AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.	Treatment 1 Day 1 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study	An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.	From Pre-dose on Day 1 to Day 48
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)	To determine if there are any clinically significant laboratory abnormalities, the haematological, clinical chemistry (serum) and urinalysis safety tests were assessed against the criteria specified in the sponsor reporting standards. Tests including Ery. Mean Corpuscular Hemoglobin, Eosinophils, Activated Partial Thromboplastin Time, Bilirubin, Fibrinogen, URINE Hemoglobin, Nitrite, and Leukocyte Esterase tests.	From pre-dose on Day 1 to Day 3
Number of Participants With Vital Signs of Potential Clinical Concern	Single supine blood pressure and pulse rate tests were assessed against the criteria specified in the sponsor reporting standards.	From pre-dose on Day 1 to Day 3
Number of Participants With ECG Values of Potential Clinical Concern	QT interval, QTc, PR, RR, QRS and heart rate tests were assessed against the criteria specified in the sponsor reporting standards.	From pre-dose on Day 1 to Day 3
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Time to First Occurrence of Cmax (Tmax)	Tmax was defined as time to first occurrence of Cmax	Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Tmax	Tmax was defined as time to first occurrence of Cmax.	Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Terminal Half-life (t½)	t½ was defined as terminal half-life of Dabigatran (Total) PK Parameters (PF-07321332/ritonavir co-administered with dabigatran.	Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): t½	t½ was defined as terminal half-life of Dabigatran (Total).	Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
Plasma PF-07321332 PK Parameters: Cmax		Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Plasma PF-07321332 PK Parameters: AUCtau	AUCtau was defined as area under the plasma concentration-time profile from time zero to time tau (τ) the dosing interval, where tau=12 hours for twice daily (BID) dosing.	Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Plasma PF-07321332 PK Parameters: t½	t½ was defined as terminal half-life of PF-07321332.	Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Plasma PF-07321332 PK Parameters: Tmax	Tmax was defined as time to first occurrence of Cmax.	Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Plasma PF-07321332 PK Parameters: CL/F	CL/F was defined as apparent clearance of drug from plasma.	Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Plasma PF-07321332 PK Parameters: Vz/F	Vz/F was defined as apparent volume of distribution.	Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Actual): December 6, 2021
• Study Completion (Actual): December 6, 2021

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; protease inhibitor; Dabigatran; ritonavir; Drug Drug Interaction; P-gp Substrate; SARS-Co-V2
• 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; Nirmatrelvir
• Other Study ID Numbers: C4671012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No