Drug-Drug Interaction Study to Estimate the Effect of PF-07321332/Ritonavir and Ritonavir on Midazolam in Healthy Participants

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT05032950

Collaborator

(none)

Enrollment

Location

Arms

2.7

Actual Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to estimate the effect PF-07321332/Ritonavir and Ritonavir on Midazolam (a cytochrome P450 [CYP]3A4 substrate) in Healthy Adult Participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: Midazolam Drug: PF-07321332/ritonavir + Midazolam Drug: Ritonavir + Midazolam	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This is a Phase I, crossover, 3-treatment, 6-sequence study to evaluate the effect of PF-07321332/ritonavir and ritonavir on the PK of midazolam in healthy participants. Midazolam is a substrate for CYP3A4. A total of approximately 12 healthy male and/or female participants will be enrolled into the study.This is a Phase I, crossover, 3-treatment, 6-sequence study to evaluate the effect of PF-07321332/ritonavir and ritonavir on the PK of midazolam in healthy participants. Midazolam is a substrate for CYP3A4. A total of approximately 12 healthy male and/or female participants will be enrolled into the study.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

COVID-19: 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 MIDAZOLAM IN HEALTHY PARTICIPANTS.

Actual Study Start Date :

Sep 17, 2021

Actual Primary Completion Date :

Dec 9, 2021

Actual Study Completion Date :

Dec 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment A Midazolam orally	Drug: Midazolam Midazolam administered as a single dose on Day 1
Experimental: Treatment B PF-07321332/ritonavir orally + Midazolam orally	Drug: PF-07321332/ritonavir + Midazolam PF-07321332/ritonavir: Administered orally every 12 hours for a total of 9 doses on Days 1-5 Midazolam: Administered orally as a single dose on Day 5
Active Comparator: Treatment C Ritonavir orally + Midazolam orally	Drug: Ritonavir + Midazolam Ritonavir: Administered orally every 12 hours for a total of 9 doses on Day1-5. Midazolam: Administered orally as a single dose on Day 5

Arm

Intervention/Treatment

Active Comparator: Treatment A

Midazolam orally

Drug: Midazolam

Midazolam administered as a single dose on Day 1

Experimental: Treatment B

PF-07321332/ritonavir orally + Midazolam orally

Drug: PF-07321332/ritonavir + Midazolam

PF-07321332/ritonavir: Administered orally every 12 hours for a total of 9 doses on Days 1-5 Midazolam: Administered orally as a single dose on Day 5

Active Comparator: Treatment C

Ritonavir orally + Midazolam orally

Drug: Ritonavir + Midazolam

Ritonavir: Administered orally every 12 hours for a total of 9 doses on Day1-5. Midazolam: Administered orally as a single dose on Day 5

Outcome Measures

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax) of midazolam when administered alone [Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose]
Cmax of midazolam when administered with PF-07321332/ritonavir [Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of midazolam when administered alone [Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose]
AUCinf of midazolam when administered with PF-07321332/ritonavir [Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of midazolam when administered alone [Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose]
AUClast of midazolam when administered with PF-07321332/ritonavir [Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]

Secondary Outcome Measures

Assessment of Participants With Treatment-Emergent Adverse Events (TEAEs) of PF-07321332/Ritonavir [Baseline up to Day 28]
Assessment of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities of PF-07321332/Ritonavir [Baseline up to Day 28]
Assessment of Participants With Clinically Significant Change From Baseline in Vital Signs of PF-07321332/Ritonavir [Baseline up to Day 28]
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings of PF-07321332/Ritonavir [Baseline up to Day 28]
Cmax of midazolam when administered with ritonavir [Treatment C: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
AUCinf of midazolam when administered with ritonavir [Treatment C: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
AUClast of midazolam when administered with ritonavir [Treatment C: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
Apparent Oral Clearance (CL/F) of midazolam when administered alone [Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose]
CL/F of midazolam when administered with PF-07321332/ritonavir [Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
Apparent Oral Volume of Distribution (Vz/F)) of midazolam when administered alone [Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose]
Vz/F of midazolam when administered with PF-07321332/ritonavir [Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
Time to Cmax (Tmax) of midazolam when administered alone [Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose]
Tmax of midazolam when administered with PF-07321332/ritonavir [Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]
Plasma Decay Half-Life (t1/2) of midazolam when administered alone [Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose]
t1/2 of midazolam when administered with PF-07321332/ritonavir [Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Female participants of childbearing potential must have a negative (urine or serum) pregnancy test.
Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

Positive test result for SARS-CoV-2 infection at the time of Screening or Day -1.
Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
Clinically relevant abnormalities requiring treatment (eg, acute myocardial infarction, unstable ischemic conditions, evidence of ventricular dysfunction, serious tachy or brady arrhythmias) or indicating serious underlying heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure greater than New York Heart Association (NYHA) 1, underlying structural heart disease, Wolff Parkinson-White syndrome).
Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or hepatitis C virus (HCVAb). Hepatitis B vaccination is allowed.
Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg, Contact with positive case, residence, or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.