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Biological AvailabilityPhase 1NCT05544786

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.

A Phase 1 study testing Nirmatrelvir/ ritonavir and Nirmatrelvir/Ritonavir in people with Biological Availability, run by Pfizer at 1 site in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Biological Availability
What is being tested?
Nirmatrelvir/ ritonavir and Nirmatrelvir/Ritonavir
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteBelgium
Study dates
28 Sep 2022to 29 Nov 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • Pfizer Clinical Research Unit - Brussels

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

Other trials in Belgium

About this study

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

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.

Being tested
Nirmatrelvir/ ritonavir, Nirmatrelvir/Ritonavir
Keywords
Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Nirmatrelvir, Paxlovid
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nirmatrelvir/ ritonavirDrug

    Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition

  • Nirmatrelvir/RitonavirDrug

    Single oral dose of nirmatrelvir/ritonavir mixed in water under fasted condition

  • Nirmatrelvir/RitonavirDrug

    Single oral dose of nirmatrelvir/ritonavir mixed in infant formula under fasted condition

  • Nirmatrelvir/ritonavirDrug

    Single oral dose of nirmatrelvir/ritonavir mixed in vanilla pudding under fasted condition

  • Nirmatrelvir/ritonavirDrug

    Single oral dose of nirmatrelvir/ritonavir mixed in vanilla pudding under fed condition

Study groups in NCT05544786
Study groupRoleWhat they receive
Treatment A: Nirmatrelvir/ritonavirActive comparatorNirmatrelvir and ritonavir tablets
Receives: Drug: Nirmatrelvir/ ritonavir
Treatment B: Nirmatrelvir/ ritonavirExperimentalNirmatrelvir/ritonavir with water
Receives: Drug: Nirmatrelvir/Ritonavir
Treatment C: Nirmatrelvir/ ritonavirExperimentalNirmatrelvir/ ritonavir with infant formula
Receives: Drug: Nirmatrelvir/Ritonavir
Treatment D: Nirmatrelvir/ ritonavirExperimentalNirmatrelvir/ ritonavir with vanilla pudding
Receives: Drug: Nirmatrelvir/ritonavir
Treatment E: Nirmatrelvir/ ritonavirExperimentalNirmatrelvir/ ritonavir with food and vanilla pudding
Receives: Drug: Nirmatrelvir/ritonavir

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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.

  2. 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.

    Measured: 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.

  3. 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.

    Measured: 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.

  4. 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.

    Measured: 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.

  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.

    Measured: 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.

  6. 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.

    Measured: 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)
  1. AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions

    AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. AUCinf for nirmatrelvir (under fasted/fed conditions) 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.

    Measured: 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.

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

    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 (under fasted/fed conditions) was calculated by linear/log trapezoidal method.

    Measured: 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.

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

    Cmax was defined maximum observed concentration. Cmax for nirmatrelvir (under fasted/fed conditions) was observed directly from data.

    Measured: 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.

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

    AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. AUCinf for ritonavir (under fasted/fed conditions) 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.

    Measured: 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.

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

    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 (under fasted/fed conditions) was calculated by linear/log trapezoidal method.

    Measured: 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.

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

    Cmax was defined maximum observed concentration. Cmax for ritonavir (under fasted/fed conditions) was observed directly from data.

    Measured: 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.

  7. Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)

    An adverse event (AE) was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study intervention and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious AE (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; suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. TEAEs included SAEs and all non-SAEs that occurred during the study.

    Measured: Baseline up to 28 days after last dose of study intervention (ie, up to 48 days).

  8. Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

    The following laboratory test abnormalities (without regard to baseline abnormality) were reported during the study: monocytes/leukocytes (percentage [%]) is larger than (>) 1.2x upper limit of normal (ULN), specific gravity (scalar) >1.030, and urine hemoglobin was larger or equal to (>=) 1.

    Measured: Baseline up to Day 4 of Period 5 (approximately 20 days)

  9. Number of Participants With Clinically Significant Vital Signs

    Supine blood pressure and pulse rate were measured with the participant's arm supported at the level of the heart and recorded after approximately 5 minutes of rest. Vital signs were done predose, 2 hours and 6 hours post dose on Day 1 of each treatment period and also on Day 4 of Period 5. Clinical significance of vital signs was determined at the investigator's discretion.

    Measured: Baseline up to Day 4 of Period 5 (approximately 20 days).

  10. Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Values

    A single 12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. All scheduled ECGs were performed after the participant has rested quietly for at least 5 minutes in a supine position. Clinical significance of ECG values was determined at the investigator's discretion.

    Measured: Baseline up to Day 4 of Period 5 (approximately 20 days).

  11. Number of Participants With Clinically Significant Physical Examination (PE) Values

    A complete physical examination included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant reported symptoms.

    Completed PE were performed by trained medical personnel at the investigator site at Screening or Period 1 Day 1 only. A brief PE might be performed at other designated time points at the discretion of the investigator. Clinical significance of physical examination values was determined at the investigator's discretion.

    Measured: Screening, Baseline up to Day 4 of Period 5 (approximately 20 days).

  12. Taste Assessment of Mouth Feel After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

    The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.

    Measured: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.

  13. Taste Assessment of Bitterness After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

    The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.

    Measured: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.

  14. Taste Assessment of Tongue/Mouth Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

    The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.

    Measured: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.

  15. Taste Assessment of Throat Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

    The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.

    Measured: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.

  16. Taste Assessment of Overall Liking After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles

    The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.

    Measured: 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2022
  2. Study start28 Sep 2022
  3. Primary completion29 Nov 2022
  4. Study completion29 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05544786
Sponsor's protocol ID
C4671036
Other IDs
2022-002497-86
Status last verified
Nov 2023
First submitted
14 Sep 2022
Last updated
10 May 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nirmatrelvir/ ritonavir and Nirmatrelvir/Ritonavir in people with Biological Availability, run by Pfizer at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles (time frame: 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.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.

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