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NCT05525910

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

Completed Phase 1 Results posted Last updated 19 September 2024
What this trial tests

Phase 1 trial testing Nirmatrelvir/ ritonavir in Biological Availability in 15 participants. Completed in 7 November 2022.

Timeline
31 August 2022
Primary endpoint
7 November 2022
7 November 2022

Quick facts

Lead sponsorPfizer
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingnone
Primary purposebasic science
Enrollment15
Start date31 August 2022
Primary completion7 November 2022
Estimated completion7 November 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Biological Availability or Healthy Participants. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · 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 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.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg27040± 36
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant29350± 28
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant30680± 21
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL28200± 40
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)33660± 29
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) Primary · 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 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.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg26620± 37
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant28890± 28
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant30350± 21
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL27630± 42
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)33060± 31
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) Primary · 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 was defined as maximum plasma concentration. Cmax for nirmatrelvir was observed directly from data.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg2709± 47
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant3111± 34
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant3181± 24
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL3051± 42
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)3556± 41
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) Primary · 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 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.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg3420± 76
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant3230± 81
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant3453± 54
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL2921± 85
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)4130± 62
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) Primary · 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 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.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg3224± 76
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant3044± 84
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant3297± 53
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL2735± 87
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)3821± 66
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) Primary · 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 was defined as maximum plasma concentration. Cmax for ritonavir was observed directly from data.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg371.3± 67
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant334.2± 93
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant374.5± 47
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL319.5± 84
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)411.3± 77
Number of Participants With All-Causality and Treatment-Related TEAEs Secondary · From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days)

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 signific

Number of participants with all-causality TEAEs
GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg2
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant2
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL1
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)2
Number of participants with all-causality SAEs
GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL0
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0
Number of participants with treatment-related TEAEs
GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL0
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0
Number of participants with treatment-related SAEs
GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL0
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis Secondary · From baseline up to Day 4 of Period 4 (approximately 17 days)

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.

Neutrophils (10^9/L) <0.8*lower limit of normal (LLN)
GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL1
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0
Monocytes/Leukocytes (%) >1.2*upper limit of normal (ULN)
GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL1
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)2
Fibrinogen (mg/dL) >1.25*baseline
GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg2
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL1
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0
Number of Participants With Clinically Significant Change From Baseline in Vital Signs Secondary · From baseline up to Day 4 of Period 4 (approximately 16 days)

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.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL0
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0
Number of Participants With Clinically Significant Physical Examination Values Secondary · From baseline up to 35 days after last dose of study treatment (ie, up to 51 days)

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.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL0
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Secondary · From baseline up to Day 4 of Period 4 (approximately 16 days)

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.

GroupValue95% CI
Nirmatrelvir/Ritonavir 300(2*150)/100 mg0
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant0
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL0
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)0

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nirmatrelvir/Ritonavir 300(2*150)/100 mg
Serious: 0/11 (0%)
Deaths: 0/11
Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant
Serious: 0/11 (0%)
Deaths: 0/11
Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant
Serious: 0/11 (0%)
Deaths: 0/11
Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL
Serious: 0/12 (0%)
Deaths: 0/12
Nirmatrelvir/Ritonavir 3*(100/33.3 mg)
Serious: 0/12 (0%)
Deaths: 0/12
Other adverse events (4 terms — click to expand)

ReactionSystemNirmatrelvir/Ritonavir 300…Nirmatrelvir/Ritonavir 2*(…Nirmatrelvir/Ritonavir 2*(…Nirmatrelvir/Ritonavir 2*(…Nirmatrelvir/Ritonavir 3*(…
Upper respiratory tract infectionInfections and infestations
ConstipationGastrointestinal disorders
WoundInjury, poisoning and procedural complications
Dry skinSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT05525910 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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