Drug-Drug Interaction Study to Estimate the Effect of PF-07321332/Ritonavir and Ritonavir on Midazolam in Healthy Participants
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 |
---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
Inclusion Criteria:
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Female participants of childbearing potential must have a negative (urine or serum) pregnancy test.
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Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
Exclusion Criteria:
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Positive test result for SARS-CoV-2 infection at the time of Screening or Day -1.
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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).
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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).
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Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
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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.
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Brussels Clinical Research Unit | Brussels | Bruxelles-capitale, RĂ©gion DE | Belgium | B-1070 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- C4671013
- 2021-003590-62