Clinical trial NCT05544786: 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.
Official title: A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE DOSE, CROSSOVER STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF NIRMATRELVIR (PF-07321332) /RITONAVIR ORAL POWDER IN 3 DIFFERENT FOOD DELIVERY VEHICLES RELATIVE TO THE NIRMATRELVIR (PF-07321332) /RITONAVIR COMMERCIAL TABLETS UNDER FASTED CONDITIONS, AND THE EFFECT OF FOOD ON RELATIVE BIOAVAILABILITY OF NIRMATRELVIR (PF-07321332) /RITONAVIR ORAL POWDER IN HEALTHY ADULT PARTICIPANTS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Biological Availability
Keywords: Coronavirus disease 2019 (COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Nirmatrelvir
Paxlovid
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-09-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 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.
measure: AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 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.
measure: Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 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.
measure: AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 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.
measure: AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 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.
measure: Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 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:
measure: AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions
timeFrame: 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.
measure: AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions
timeFrame: 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.
measure: Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions
timeFrame: 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.
measure: AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions
timeFrame: 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.
measure: AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions
timeFrame: 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.
measure: Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions
timeFrame: 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.
measure: Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 28 days after last dose of study intervention (ie, up to 48 days).
measure: Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
timeFrame: Baseline up to Day 4 of Period 5 (approximately 20 days)
measure: Number of Participants With Clinically Significant Vital Signs
timeFrame: Baseline up to Day 4 of Period 5 (approximately 20 days).
measure: Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Values
timeFrame: Baseline up to Day 4 of Period 5 (approximately 20 days).
measure: Number of Participants With Clinically Significant Physical Examination (PE) Values
timeFrame: Screening, Baseline up to Day 4 of Period 5 (approximately 20 days).
measure: Taste Assessment of Mouth Feel After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.
measure: Taste Assessment of Bitterness After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.
measure: Taste Assessment of Tongue/Mouth Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.
measure: Taste Assessment of Throat Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.
measure: Taste Assessment of Overall Liking After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
timeFrame: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Pfizer Clinical Research Unit - Brussels
state: Bruxelles-capitale, Région DE
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: