Clinical trial NCT05064800: PF-07321332/Ritonavir and Ritonavir on Dabigatran Study in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Drug Drug Interaction
Dabigatran
P-gp Substrate
SARS-Co-V2
COVID-19
protease inhibitor
ritonavir
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-10-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention 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
Primary purpose: BASIC_SCIENCE

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


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

Primary outcomes:
measure: Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Maximum Plasma Concentration (Cmax)
timeFrame: 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
measure: Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUCinf
timeFrame: 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
measure: Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUClast
timeFrame: 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:
measure: Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Maximum Plasma Concentration (Cmax)
timeFrame: 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
measure: Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinf
timeFrame: 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
measure: Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClast
timeFrame: 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
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From Study
timeFrame: From Pre-dose on Day 1 to Day 48
measure: Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)
timeFrame: From pre-dose on Day 1 to Day 3
measure: Number of Participants With Vital Signs of Potential Clinical Concern
timeFrame: From pre-dose on Day 1 to Day 3
measure: Number of Participants With ECG Values of Potential Clinical Concern
timeFrame: From pre-dose on Day 1 to Day 3
measure: Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Time to First Occurrence of Cmax (Tmax)
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
measure: Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): Tmax
timeFrame: Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
measure: Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Terminal Half-life (t½)
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
measure: Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): t½
timeFrame: Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose
measure: Plasma PF-07321332 PK Parameters: Cmax
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
measure: Plasma PF-07321332 PK Parameters: AUCtau
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
measure: Plasma PF-07321332 PK Parameters: t½
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
measure: Plasma PF-07321332 PK Parameters: Tmax
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
measure: Plasma PF-07321332 PK Parameters: CL/F
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
measure: Plasma PF-07321332 PK Parameters: Vz/F
timeFrame: Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood )
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: