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

Phase 1
Completed
Conditions
Healthy Participants
Interventions
Registration Number
NCT05064800
Lead Sponsor
Pfizer
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Treatment BPF-07321332/ritonavir + DabigatranPF-07321332/ritonavir + Dabigatran
Treatment CRitonavir + DabigatranRitonavir + Dabigatran
Treatment ADabigatranDabigatran only
Primary Outcome Measures
NameTimeMethod
Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): 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 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose

Cmax was defined as maximum observed plasma concentration.

Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUCinfTreatment 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

AUCinf was defined as the area under the plasma concentration-time curve from time 0 extrapolated to infinity

Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): AUClastTreatment 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

AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Laboratory Test Abnormality (Without Regard to Baseline Abnormality)From pre-dose on Day 1 to Day 3

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.

Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUCinfTreatment 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

AUCinf was defined as area under the plasma concentration-time curve from time 0 extrapolated to infinity

Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): AUClastTreatment 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

AUClast was defined as area under the plasma concentration time curve from time 0 to the time of the last measurable concentration.

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

Cmax was defined as maximum observed plasma concentration

Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): TmaxTreatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose

Tmax was defined as time to first occurrence of Cmax.

Plasma Dabigatran (Total) PK Parameters (Ritonavir Co-administered With Dabigatran [Treatment 3]): t½Treatment 3 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose

t½ was defined as terminal half-life of Dabigatran (Total).

Number of Participants With Vital Signs of Potential Clinical ConcernFrom pre-dose on Day 1 to Day 3

Single supine blood pressure and pulse rate tests were assessed against the criteria specified in the sponsor reporting standards.

Plasma PF-07321332 PK Parameters: AUCtauTreatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose

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.

Plasma PF-07321332 PK Parameters: t½Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose

t½ was defined as terminal half-life of PF-07321332.

Plasma PF-07321332 PK Parameters: Vz/FTreatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose

Vz/F was defined as apparent volume of distribution.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs , and TEAEs Leading to Participant Discontinuation From StudyFrom Pre-dose on Day 1 to Day 48

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.

Number of Participants With ECG Values of Potential Clinical ConcernFrom pre-dose on Day 1 to Day 3

QT interval, QTc, PR, RR, QRS and heart rate tests were assessed against the criteria specified in the sponsor reporting standards.

Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Time to First Occurrence of Cmax (Tmax)Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose

Tmax was defined as time to first occurrence of Cmax

Plasma Dabigatran (Total) PK Parameters (PF-07321332/Ritonavir Co-administered With Dabigatran [Treatment 2]): Terminal Half-life (t½)Treatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose

t½ was defined as terminal half-life of Dabigatran (Total) PK Parameters (PF-07321332/ritonavir co-administered with dabigatran.

Plasma PF-07321332 PK Parameters: CmaxTreatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose
Plasma PF-07321332 PK Parameters: CL/FTreatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose

CL/F was defined as apparent clearance of drug from plasma.

Plasma PF-07321332 PK Parameters: TmaxTreatment 2 Day 2 pre-dose, and at 1, 2, 4, 6, 8, 12 hours post-dose

Tmax was defined as time to first occurrence of Cmax.

Trial Locations

Locations (1)

Research Centers of America ( Hollywood )

🇺🇸

Hollywood, Florida, United States

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