The purpose of this study is to estimate the relative bioavailability of PF-07321332 in different formulations in healthy adult participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
PF-07321332 ritonavir will be administered as single dose orally
PF-07321332 ritonavir will be administered as single oral dose orally.
PF-07321332 ritonavir will be administered as single oral dose orally.
Pfizer Clinical Research Unit - New Haven
New Haven, Connecticut, United States
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir
AUClast for nirmatrelvir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUClast for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir
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. Natural log-transformed AUCinf for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUCinf for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
Maximum Plasma Concentration (Cmax) of Nirmatrelvir
Cmax for nirmatrelvir was observed directly from data. Natural log-transformed Cmax for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed Cmax for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
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PF-07321332 ritonavir will be administered as single oral dose orally.
PF-07321332 will be administered as single oral dose orally.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs might arise from symptoms or other complaints reported to the investigator by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative), or they might arise from clinical findings of the investigator or other healthcare providers (clinical signs, test results, etc.). TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.
Time frame: Baseline up to 35 days after last dose of study intervention (up to 12 weeks)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
The laboratory abnormality parameters included Chemistry: bicarbonate (milliequivalents per liter \[mEq/L\]) \<0.9 x lower limit of normal (LLN), urobilinogen (ehrlich units per deciliter \[EU/dL\]) \>=1, and fibrinogen (milligram/deciliter \[mg/dL\]) \>1.25 x baseline; Urinalysis: URINE hemoglobin (Scalar) \>=1, only those categories in which at least 1 participant had data were reported. All the safety laboratory samples were collected following at least a 4 hour fast. Clinical laboratory evaluations only included treatments of nirmatrelvir SDD suspension/ritonavir 300/100 mg and nirmatrelvir SDD suspension 300 mg. No participant was evaluable for clinical laboratory evaluations for the other treatments.
Time frame: Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose) and Day4 of Period 5 (4 days after the last dose on study discharge day). Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period
Number of Participants With Vital Signs Abnormalities
Single supine blood pressure (BP) and pulse rate (PR) were measured with the participant's arm supported at the level of the heart and recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm (preferably the dominant arm) was used throughout the study. Participants were instructed not to speak during measurements.
Time frame: Screening (D28-D2), D1 of Period 1 (before 1st dose), D1 hr 0,2,and 6 of each period, and D4 of Period 5 (4 days after the last dose on study discharge day). Each treatment Period was 4 days long (D1-D4) with a minimum 4 days washout between each period
Number of Participants With ECG Abnormalities
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) were collected. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position.
Time frame: Screening (from D-28 to D-2), D1, hr0 of Period 1 (before 1st dose) and D4 of Period 5 (4 days after last dose on study discharge day). Each treatment period was 4 days long (D1 to D4) with a minimum of 4 days washout between each period
Number of Participants With Physical Examination Abnormalities
A complete PE 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.
Time frame: Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose. Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period