Relative Bioavailability Study of Nirmatrelvir/Ritonavir 4 Different Fixed Dose Combination Tablets Relative to the Commercial Tablets in Healthy Participants

A Phase 1, Open-Label, Randomized, Single Dose, Crossover Study to Estimate the Relative Bioavailability of Nirmatrelvir and Ritonavir Following Oral Administration of 4 Different Fixed Dose Combination Tablet Formulations Relative to The Commercial Tablet Formulation in Healthy Adult Participants Under Fasted Conditions

The purpose of this study is to estimate the relative bioavailability of nirmatrelvir/ritonavir of 4 different FDC tablet formulations relative to the commercial tablet formulation under fasted conditions in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants; Biological Availability
• Intervention / Treatment: Drug: Nirmatrelvir/ ritonavir; Drug: Nirmatrelvir/ritonavir

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination (PE), laboratory tests, vital signs and standard 12 lead ECGs.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures

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, hepatitis B surface antigen (HBsAg), or hepatitis B surface antibody (HCVAb). Hepatitis B vaccination is allowed.
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
• Participant who have received a COVID-19 vaccine within 7 days before screening or admission, or who are to be vaccinated with a COVID-19 vaccine at any time during the study confinement period.
• A positive urine drug test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A: Nirmatrelvir/ritonavir; Nirmatrelvir and ritonavir tablets	Drug: Nirmatrelvir/ ritonavir; Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition
Experimental: Treatment B: Nirmatrelvir/ ritonavir; Nirmatrelvir/ ritonavir test tablets	Drug: Nirmatrelvir/ritonavir; Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition
Experimental: Treatment C: Nirmatrelvir/ ritonavir; Nirmatrelvir/ ritonavir test tablets	Drug: Nirmatrelvir/ritonavir; Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition
Experimental: Treatment D: Nirmatrelvir/ ritonavir; Nirmatrelvir/ ritonavir test tablets	Drug: Nirmatrelvir/ ritonavir; Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition
Experimental: Treatment E: Nirmatrelvir/ ritonavir; Nirmatrelvir/ ritonavir test tablets	Drug: Nirmatrelvir/ ritonavir; Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under curve from time zero to 72 hours post dose	0 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours
Peak plasma concentration (Cmax)	0 , 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)	Baseline (Day 0) up to 28 days after last dose of study medication
Number of Participants With Notable Electrocardiogram (ECG) Values	Baseline (Day 0) up to day 4 of treatment period 4
Number of Participants With Clinically Notable Vital Signs	Baseline (Day 0) up to day 4 of treatment period 4
Number of Participants With Clinically Notable Changes in Clinical laboratory	Baseline (Day 0) up to day 4 of treatment period 4
Number of Participants With Clinically Notable Abnormality in physical examination	Baseline (Day 0) up to day 4 of treatment period 4

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Actual): November 7, 2022
• Study Completion (Actual): November 7, 2022

Study Registration Dates

• First Submitted: August 31, 2022
• First Submitted That Met QC Criteria: August 31, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): December 16, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Paxlovid; Nirmatrelvir; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Coronavirus disease 2019 (COVID-19)
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir
• Other Study ID Numbers: C4671023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No