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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05032950
Recruitment Status : Completed
First Posted : September 2, 2021
Last Update Posted : January 19, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
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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
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Study Type : Interventional  (Clinical Trial)
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.
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 : September 17, 2021
Actual Primary Completion Date : December 9, 2021
Actual Study Completion Date : December 9, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
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Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of midazolam when administered alone [ Time Frame: Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose ]
  2. Cmax of midazolam when administered with PF-07321332/ritonavir [ Time Frame: Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  3. Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of midazolam when administered alone [ Time Frame: Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose ]
  4. AUCinf of midazolam when administered with PF-07321332/ritonavir [ Time Frame: Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  5. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of midazolam when administered alone [ Time Frame: Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose ]
  6. AUClast of midazolam when administered with PF-07321332/ritonavir [ Time Frame: 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 :
  1. Assessment of Participants With Treatment-Emergent Adverse Events (TEAEs) of PF-07321332/Ritonavir [ Time Frame: Baseline up to Day 28 ]
  2. Assessment of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities of PF-07321332/Ritonavir [ Time Frame: Baseline up to Day 28 ]
  3. Assessment of Participants With Clinically Significant Change From Baseline in Vital Signs of PF-07321332/Ritonavir [ Time Frame: Baseline up to Day 28 ]
  4. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings of PF-07321332/Ritonavir [ Time Frame: Baseline up to Day 28 ]
  5. Cmax of midazolam when administered with ritonavir [ Time Frame: Treatment C: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  6. AUCinf of midazolam when administered with ritonavir [ Time Frame: Treatment C: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  7. AUClast of midazolam when administered with ritonavir [ Time Frame: Treatment C: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  8. Apparent Oral Clearance (CL/F) of midazolam when administered alone [ Time Frame: Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose ]
  9. CL/F of midazolam when administered with PF-07321332/ritonavir [ Time Frame: Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  10. Apparent Oral Volume of Distribution (Vz/F)) of midazolam when administered alone [ Time Frame: Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose ]
  11. Vz/F of midazolam when administered with PF-07321332/ritonavir [ Time Frame: Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  12. Time to Cmax (Tmax) of midazolam when administered alone [ Time Frame: Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose ]
  13. Tmax of midazolam when administered with PF-07321332/ritonavir [ Time Frame: Treatment B: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hour post-dose ]
  14. Plasma Decay Half-Life (t1/2) of midazolam when administered alone [ Time Frame: Treatment A: Day 1 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 and 36 hour post-dose ]
  15. t1/2 of midazolam when administered with PF-07321332/ritonavir [ Time Frame: 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
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05032950


Locations
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Belgium
Brussels Clinical Research Unit
Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
More Information
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Additional Information:

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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05032950    
Other Study ID Numbers: C4671013
2021-003590-62 ( EudraCT Number )
First Posted: September 2, 2021    Key Record Dates
Last Update Posted: January 19, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Drug-drug interaction
Midazolam
COVID-19 (Coronavirus disease 2019)
SARS-CoV (severe acute respiratory syndrome coronavirus)
Additional relevant MeSH terms:
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Ritonavir
Nirmatrelvir
Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
 GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors