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

NCT05525910 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4671023
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biological Availability; Healthy Participants

Keywords

Coronavirus disease 2019 (COVID-19); Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Nirmatrelvir; Paxlovid

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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 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)

  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 ritonavir was calculated by Linear/Log trapezoidal method.

  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 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)

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

  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

Secondary Outcomes (5)

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

  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

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

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

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

• Number of Participants With Clinically Significant Physical Examination Values

  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)

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

Study Arms (5)

Treatment A: Nirmatrelvir/ritonavir

ACTIVE COMPARATOR

Nirmatrelvir and ritonavir tablets

Drug: Nirmatrelvir/ ritonavir

Treatment B: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ ritonavir test tablets

Drug: Nirmatrelvir/ritonavir

Treatment C: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ ritonavir test tablets

Drug: Nirmatrelvir/ritonavir

Treatment D: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ ritonavir test tablets

Drug: Nirmatrelvir/ ritonavir

Treatment E: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ ritonavir test tablets

Drug: Nirmatrelvir/ ritonavir

Interventions

Nirmatrelvir/ ritonavir DRUG

Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition

Treatment A: Nirmatrelvir/ritonavir

Nirmatrelvir/ritonavir DRUG

Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition

Treatment B: Nirmatrelvir/ ritonavir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

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

MeSH Terms

Conditions

COVID-19

Interventions

nirmatrelvir and ritonavir drug combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 2, 2022
• Study Start: August 31, 2022
• Primary Completion: November 7, 2022
• Study Completion: November 7, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)