Drug-Drug Interaction Study to Estimate the Effect of PF-07321332/Ritonavir and Ritonavir on Midazolam in Healthy Participants
Condition: Healthy Participants
Intervention: Midazolam; PF-07321332/ritonavir + Midazolam; Ritonavir + Midazolam
Intervention description: Midazolam administered as a single dose on Day 1; 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; 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
Intervention MeSH terms: Ritonavir; Nirmatrelvir; Midazolam
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
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.
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Drug-drug interaction; Midazolam; COVID-19 (Coronavirus disease 2019); SARS-CoV (severe acute respiratory syndrome coronavirus)

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female participants of childbearing potential must have a negative (urine or serum)
             pregnancy test.

          2. Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

             -

        Exclusion Criteria:

          1. Positive test result for SARS-CoV-2 infection at the time of Screening or Day -1.

          2. 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).

          3. 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).

          4. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).

          5. 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.

          6. 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.