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

Pfizer15 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Biological Availability Healthy Participants

Interventions

Nirmatrelvir/ ritonavirDRUG

Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition

Nirmatrelvir/ritonavirDRUG

Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition

Nirmatrelvir/ritonavirDRUG

Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

New Haven Clinical Research Unit

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)

AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time. AUCinf for nirmatrelvir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each treatment period

AUClast of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)

AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (Clast). AUClast for nirmatrelvir was calculated by Linear/Log trapezoidal method.

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each treatment period

Cmax of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)

Cmax was defined as maximum plasma concentration. Cmax for nirmatrelvir was observed directly from data.

Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each treatment period

AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)

AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time. AUCinf for ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.

Data from ClinicalTrials.gov

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Secondary Outcomes

Number of Participants With All-Causality and Treatment-Related TEAEs

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study treatment and up to approximately 51 days that were absent before treatment or that worsened relative to pretreatment state.

Time frame: From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days)

Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis

Hematology included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, etc. Chemistry included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, fibrinogen, etc. Urinalysis included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy and culture. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. Baseline was defined as the last measurement taken prior to first dosing (Period 1 Day -1).

Time frame: From baseline up to Day 4 of Period 4 (approximately 17 days)

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Vital signs (temperature, pulse rate and blood pressure) were obtained with participants following at least 5 minutes of supine rest. Clinical significance of vital signs was determined at the investigator's discretion. Baseline was defined as pre-dose measurement taken on Day 1 of each period.

Time frame: From baseline up to Day 4 of Period 4 (approximately 16 days)

Number of Participants With Clinically Significant Physical Examination Values

A complete physical examination (PE) included, at a minimum, height, weight, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief PE included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant-reported symptoms. Clinical significance of physical examination values was determined at the investigator's discretion.

Time frame: From baseline up to 35 days after last dose of study treatment (ie, up to 51 days)

Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG)

A 12-lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured pulse rate, QT, and QTc intervals and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. Clinical significance of ECG values was determined at the investigator's discretion. Baseline was defined as pre-dose measurement taken on Day 1 of Period 1.

Time frame: From baseline up to Day 4 of Period 4 (approximately 16 days)