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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Biological Availability, Healthy Participants

Intervention / Treatment
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* Drug: Nirmatrelvir/ ritonavir
* Drug: Nirmatrelvir/ritonavir
* Drug: Nirmatrelvir/ritonavir
* Drug: Nirmatrelvir/ ritonavir
* Drug: Nirmatrelvir/ ritonavir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Nirmatrelvir, Paxlovid