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

NCT05064800 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4671012
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Participants

Keywords

Drug Drug Interaction; Dabigatran; P-gp Substrate; SARS-Co-V2; COVID-19; protease inhibitor; ritonavir

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (17)

• Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Maximum Plasma Concentration (Cmax)

  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

  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

  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

  From Pre-dose on Day 1 to Day 48

• Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)

  From pre-dose on Day 1 to Day 3

Study Arms (3)

Treatment A

ACTIVE COMPARATOR

Dabigatran only

Drug: Dabigatran

Treatment B

EXPERIMENTAL

PF-07321332/ritonavir + Dabigatran

Drug: PF-07321332/ritonavir + Dabigatran

Treatment C

ACTIVE COMPARATOR

Ritonavir + Dabigatran

Drug: Ritonavir + Dabigatran

Interventions

Dabigatran DRUG

A single dose of Dabigatran on Day 1

Treatment A

PF-07321332/ritonavir + Dabigatran DRUG

PF-07321332/ritonavir twice daily (BID) for Days 1 and 2 Single dose of Dabigatran on Day 2

Treatment B

Ritonavir + Dabigatran DRUG

Ritonavir BID on Days 1 and 2 Single dose of Dabigatran on Day 2

Treatment C

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research Centers of America ( Hollywood )

Hollywood, Florida, 33024, United States

Location

Related Publications (2)

• Cox DS, Rehman M, Khan T, Ginman K, Salageanu J, LaBadie RR, Wan K, Damle B. Effects of nirmatrelvir/ritonavir on midazolam and dabigatran pharmacokinetics in healthy participants. Br J Clin Pharmacol. 2023 Nov;89(11):3352-3363. doi: 10.1111/bcp.15835. Epub 2023 Jul 12.

  PMID: 37354048 DERIVED

• Sagawa K, Lin J, Jaini R, Di L. Physiologically-Based Pharmacokinetic Modeling of PAXLOVID with First-Order Absorption Kinetics. Pharm Res. 2023 Aug;40(8):1927-1938. doi: 10.1007/s11095-023-03538-5. Epub 2023 May 25.

  PMID: 37231296 DERIVED

Related Links

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

MeSH Terms

Conditions

COVID-19

Interventions

Dabigatran; nirmatrelvir; Ritonavir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

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

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: 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

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: October 1, 2021
• Study Start: September 21, 2021
• Primary Completion: December 6, 2021
• Study Completion: December 6, 2021
• Last Updated: March 29, 2024
• Results First Posted: March 29, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)