Relative Bioavailability Study of Nirmatrelvir/Ritonavir Oral Powder Relative to the Commercial Tablets and Estimation of the Effect of Food on Bioavailability of the Nirmatrelvir/Ritonavir Oral Powder in Healthy Participants.

NCT05544786 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: C46710362022-002497-86
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to estimate the relative bioavailability (rBA) of nirmatrelvir/ritonavir oral powder in 3 different food vehicles relative to the Paxlovid® tablets under fasted condition in healthy adult participants, and to estimate the effect of food on the rBA of the nirmatrelvir/ritonavir oral powder formulation. The study will also assess the safety, tolerability, and palatability of nirmatrelvir/ritonavir oral powder in healthy adult participants.

Conditions

Biological Availability

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 Nirmatrelvir/Ritonavir in Different Delivery Vehicles

  AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.

  0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.

• AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

  AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.

• Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

  Cmax was defined maximum observed 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.

• AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

  AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.

  0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.

• AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

  AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.

• Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

  Cmax was defined maximum observed 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.

Secondary Outcomes (16)

• AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions

  0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.

• AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions

  0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.

• Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions

  0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.

• AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions

  0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.

• AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions

  0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.

Study Arms (5)

Treatment A: Nirmatrelvir/ritonavir

ACTIVE COMPARATOR

Nirmatrelvir and ritonavir tablets

Drug: Nirmatrelvir/ ritonavir

Treatment B: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ritonavir with water

Drug: Nirmatrelvir/Ritonavir

Treatment C: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ ritonavir with infant formula

Drug: Nirmatrelvir/Ritonavir

Treatment D: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ ritonavir with vanilla pudding

Drug: Nirmatrelvir/ritonavir

Treatment E: Nirmatrelvir/ ritonavir

EXPERIMENTAL

Nirmatrelvir/ ritonavir with food and vanilla pudding

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 mixed in water 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)

Pfizer Clinical Research Unit - Brussels

Brussels, Bruxelles-capitale, Région de, B-1070, Belgium

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: September 14, 2022
• First Posted: September 16, 2022
• Study Start: September 28, 2022
• Primary Completion: November 29, 2022
• Study Completion: November 29, 2022
• Last Updated: May 10, 2024
• Results First Posted: May 10, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)