Healthy Participants
Conditions
Brief summary
A Phase 1, double blind, sponsor open, single and multiple ascending dose study to evaluate safety, tolerability and pharmacokinetics of PF-07321332 in healthy participants.
Detailed description
Combined 5-part study. Part-1: Single Ascending dose Part-2: Multiple Ascending Dose Part-3: Relative bioavailability and food effect Part-4: Metabolism and Excretion Part-5: Supra-therapeutic Exposure Part-1,2 and 5 are double blind, sponsor open and Part-3 and 4 are open label study.
Interventions
DRUGPF-07321332 Dose 1
PF-07321332 Dose 1 or Placebo
DRUGPF-07321332 Dose 2
PF-07321332 Dose 2 or Placebo
DRUGPF-07321332 Dose 3
PF-07321332 Dose 3 or Placebo
DRUGPF-07321332 Dose 4
PF-07321332 Dose 4 or Placebo
DRUGPF-07321332 Dose 5
PF-07321332 Dose 5 or Placebo
DRUGPF-07321332 Dose 4 or Placebo (Fed)
PF-07321332 Dose 5 or Placebo with high fat meal
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female subjects between ages of 18-60 years. Male only in part-4. * Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight \>50kg (110lbs) * Japanese subjects who have four Japanese biologic grandparents born in Japan
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) * Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, intestinal resection). * Positive test result for SARS-CoV-2 infection at the time of screening or Day-1. * Have received COVID-19 vaccine within 7 days before screening or have received only one of the 2 required doses of COVID-19 vaccine * Use of tobacco or nicotine containing products in excess of the equivalents of 5 cigarettes per day or 2 chews of tobacco per day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Post the single dose of study intervention till up to 36 days | An Adverse Event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. 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 significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | Baseline up to Day 2 of the final period | Vital signs (temperature, respiratory rate, pulse rate \[PR\], systolic blood pressure \[SBP\], and diastolic blood pressure \[DBP\]) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 millimeters of mercury (mm Hg), increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 beats per minute (bpm) or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of study intervention and had at least 1 assessment undertaken post treatment. |
| Number of Participants With Laboratory Abnormalities in PART-1: SAD | Baseline up to Day 4 of the final period | Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, Severe Acute Respiratory Syndrome Coronavirus 2 \[SARS-CoV-2\] reverse transcription polymerase chain reaction \[RT-PCR\], estimated glomerular filtration rate \[eGFR\], pregnancy test \[beta human chorionic gonadotropin \[b-hCG\]\], activated partial thromboplastin time \[aPTT\], prothrombin time \[PT\] - international normalized ratio \[INR\], fibrinogen, thyroid stimulating hormone \[TSH\], Free thyroxine \[T4\]). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention. |
| Number of Participants With TEAEs in PART-2:MAD | Post first dose till up to 45 days after last dose of study intervention | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | Baseline up to Day 12 | Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 mm Hg, increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 bpm or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion. |
| Number of Participants With Laboratory Abnormalities in PART-2: MAD | Baseline up to Day 12 | Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention. |
| Area Under the Plasma Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Tablet Formulation and Suspension in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. |
| Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Tablet Formulation and Suspension in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. Natural log transformed AUCinf for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet\] /Reference \[suspension\]) and 90% CI for the ratio. |
| Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | Cmax is maximum plasma concentration. It was observed directly from data. Natural log transformed Cmax for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet\] /Reference \[suspension\]) and 90% CI for the ratio. |
| Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME | Day 1 to Day 11 | Total recovery of drug-related material excreted in urine, expressed as a percent of total dose administered, measured by fluorine-19 nuclear magnetic resonance (19F-NMR). |
| Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME | Day 1 to Day 11 | Total recovery of drug-related material excreted in feces, expressed as a percent of total dose administered, measured by 19F-NMR. |
| Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME | Day 1 to Day 11 | Total recovery of drug-related material excreted in urine and feces combined, expressed as a percent of total dose administered, measured by 19F-NMR. |
| Number of Participants With TEAEs in PART-5: SE | Post first dose till up to 36 days after last dose of study intervention | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE | Baseline up to Day 5 of the final period | Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 mm Hg, increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 bpm or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion. |
| Number of Participants With Laboratory Abnormalities in PART-5: SE | Baseline up to Day 5 of the final period | Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | AUCtau is area under the concentration-time profile from time 0 (pre-dose) to end of dosing interval, where dosing interval was 12 hours. AUCtau(dn) = AUCtau/dose. |
| Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Cav is average plasma concentration over the dosing interval, where dosing interval was 12 hours. |
| Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Cmin is minimum observed concentration during the dosing interval, where dosing interval was 12 hours. |
| Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Rac was calculated as Day 5 or Day 10 AUCtau/Day 1 AUCtau. |
| Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Rac,Cmax is Day 5 or Day 10 Cmax/Day 1 Cmax. |
| Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | PTR is defined as peak-to-trough ratio. PTR = Cmax/Cmin. |
| CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCtau. |
| Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration. |
| Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Aetau is the sum of (urine volume × urine concentration) for each collection over the dosing interval. |
| Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10 | Pre-dose to 12 hours post-dose on Day 10 | Aetau% is defined as percent of dose excreted in urine as unchanged drug over the dosing interval, where the dosing interval is 12 hours. Aetau% = Aetau / Dose \* 100. |
| AUClast of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. Natural log transformed AUClast for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet under fed condition\] /Reference \[tablet under fasted condition\]) and 90% CI for the ratio. |
| AUCinf of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. Natural log transformed AUCinf for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet under fed condition\] /Reference \[tablet under fasted condition\]) and 90% CI for the ratio. |
| Cmax of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | Cmax is maximum plasma concentration. It was observed directly from data. Natural log transformed Cmax for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet under fed condition\] /Reference \[tablet under fasted condition\]) and 90% CI for the ratio. |
| Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose. |
| Tmax of Plasma PF-07321332 in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | Time to reach Cmax. |
| AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. AUClast(dn) = AUClast /dose. |
| AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose. |
| CL/F of Plasma PF-07321332 in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf. |
| Vz/F of Plasma PF-07321332 in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| t1/2 of Plasma PF-07321332 in PART-3: rBA/FE | Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose | t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration. |
| Number of Participants With TEAEs in PART-3: rBA/FE | Post the single dose of study intervention till up to 36 days | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. |
| Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE | Baseline up to Day 3 | Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention. |
| Cmax of Plasma PF-07321332 in PART-4: ME | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | Cmax is maximum plasma concentration. It was observed directly from data. |
| Tmax of Plasma PF-07321332 in PART-4: ME | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | Tmax is time to reach Cmax. |
| AUClast of Plasma PF-07321332 in PART-4: ME | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. |
| Renal Clearance (CLr) in PART-2: MAD on Day 10 | Pre-dose to 12 hours post-dose on Day 10 | CLr is defined as the renal clearance. CLr = Aetau / AUCtau, where the dosing interval was 12 hours. |
| CL/F of Plasma PF-07321332 in PART-4: ME | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf. |
| Vz/F of Plasma PF-07321332 in PART-4: ME | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| t1/2 of Plasma PF-07321332 in PART-4: ME | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration. |
| Number of Participants With TEAEs in PART-4: ME | Post the single dose of study intervention till up to 36 days | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator. |
| Number of Participants With Laboratory Abnormalities in PART-4: ME | Baseline up to Day 11 | Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. |
| Cmax of Plasma PF-07321332 in PART-5: SE | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose | Cmax is maximum plasma concentration. It was observed directly from data. |
| Tmax of Plasma PF-07321332 in PART-5: SE | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose | Time to reach Cmax. |
| AUClast of Plasma PF-07321332 in PART-5: SE | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose | AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. |
| AUCinf of Plasma PF-07321332 in PART-5: SE | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose | AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. |
| t1/2 of Plasma PF-07321332 in PART-5: SE | Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose | t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration. |
| AUCinf of Plasma PF-07321332 in PART-4: ME | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. |
| Cmax of Plasma PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | Cmax is maximum plasma concentration. It was observed directly from data. |
| Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | Time to reach Cmax. |
| AUClast of Plasma PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. |
| AUCinf of PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. |
| Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose. |
| Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose. |
| Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. AUClast(dn) = AUClast /dose. |
| Apparent Volume of Distribution (Vz/F) in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Apparent Clearance (CL/F) in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf. |
| Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose | t1/2 is the time measured for the plasma concentration of drug to decrease by one half of its initial concentration. |
| Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Cmax is maximum plasma concentration. It was observed directly from data. |
| Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Time to reach Cmax. |
| Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | AUCtau is area under the concentration-time profile from time 0 (pre-dose) to end of dosing interval, where dosing interval was 12 hours. |
| Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10. | Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose. |
Countries
Belgium, United States
Participant flow
Pre-assignment details
This was a 5-part study combining PART-1: single ascending dose (SAD), PART-2: multiple ascending dose (MAD), PART-3: relative bioavailability/food effect (rBA/FE), PART-4: metabolism and excretion (M&E) and PART-5: supratherapeutic exposure (SE).
Participants by arm
| Arm | Count |
|---|---|
| PART-1: SAD Treatment Sequence 1 PF-07321332 150 mg (Suspension), Fasted=\>PF-07321332 1500 mg (Suspension), Fasted=\>Placebo (Suspension)/RTV 100 mg, Fasted Participants received a single dose of PF-07321332 150 mg under fasted condition in period 1, a single dose of PF-07321332 1500 mg under fasted condition in period 2, a single dose of placebo and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fasted condition in period 3. There was a washout interval of ≥5 days between periods. | 2 |
| PART-1: SAD Treatment Sequence 2 PF-07321332 150 mg (Suspension), Fasted=\>Placebo (Suspension), Fasted=\>PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted Participants received a single dose of PF-07321332 150 mg under fasted condition in period 1, a single dose of placebo under fasted condition in period 2, a single dose of PF-07321332 750 mg and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fasted condition in period 3. There was a washout interval of ≥5 days between periods. | 2 |
| PART-1:SAD Treatment Sequence 3 Placebo (Suspension), Fasted=\>PF-07321332 1500 mg (Suspension), Fasted=\>PF-07321332 750 mg (suspension)/RTV 100 mg, Fasted Participants received a single dose of placebo under fasted condition in period 1, a single dose of PF-07321332 1500 mg under fasted condition in period 2, a single dose of PF-07321332 750 mg and a total of 3 doses of RTV 100 mg at -12 hour (h), 0h and 12h post-dose under fasted condition in period 3. There was a washout interval of ≥5 days between periods. | 2 |
| PART-1: SAD Treatment Sequence 4 PF-07321332 500 mg (Suspension), Fasted=\>PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted=\>PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed Participants received a single dose of PF-07321332 500 mg under fasted condition in period 1, a single dose of PF-07321332 250 mg and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fasted condition in period 2, a single dose of PF-07321332 250 mg and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fed condition in period 3. There was a washout interval of ≥5 days between periods. | 2 |
| PART-1: SAD Treatment Sequence 5 PF-07321332 500 mg (Suspension), Fasted=\>Placebo (Suspension)/RTV 100 mg, Fasted=\>Placebo (Suspension)/RTV 100 mg, Fed Participants received a single dose of PF-07321332 500 mg under fasted condition in period 1, a single dose of placebo and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fasted condition in period 2, a single dose of placebo and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fed condition in period 3. There was a washout interval of ≥5 days between periods. | 3 |
| PART-1: SAD Treatment Sequence 6 Placebo (Suspension), Fasted=\>PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted=\>PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed Participants received a single dose of placebo under fasted condition in period 1, a single dose of PF-07321332 250 mg and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fasted condition in period 2, a single dose of PF-07321332 250 mg and a total of 3 doses of RTV 100 mg at -12h, 0h and 12h post-dose under fed condition in period 3. There was a washout interval of ≥5 days between periods. | 2 |
| PART-2: MAD Placebo (Suspension)/RTV 100 mg Twice Daily (BID), Fasted Participants received placebo and RTV 100 mg BID under fasted condition for 10 days. | 8 |
| PART-2: MAD PF-07321332 (Suspension)/RTV 75/100 mg BID, Fasted Participants received PF-07321332 75 mg and RTV 100 mg BID under fasted condition for 10 days. | 4 |
| PART-2: MAD PF-07321332 (Suspension)/RTV 250/100 mg BID, Fasted Participants received PF-07321332 250 mg and RTV 100 mg BID under fasted condition for 10 days. | 4 |
| PART-2: MAD PF-07321332 (Suspension)/RTV 500/100 mg BID, Fasted Participants received PF-07321332 500 mg and RTV 100 mg BID under fasted condition for 10 days. | 7 |
| PART-2: MAD Placebo (Suspension)/RTV100 mg BID, Fasted, Japanese Japanese participants received placebo and RTV 100 mg BID under fasted condition for 10 days. | 2 |
| PART-2: MAD PF-07321332 (Suspension)/RTV 250/100 mg BID, Fasted, Japanese Japanese participants received PF-07321332 250 mg and RTV 100 mg BID under fasted condition for 10 days. | 4 |
| PART-3: rBA/FE Treatment Sequence 1 PF-07321332 250 mg (Suspension), Fasted=\>PF-07321332 250 mg (Tablet), Fasted=\>PF-07321332 250 mg (Tablet), Fed Participants received a single dose of PF-07321332 250 mg (suspension) under fasted condition in period 1, PF-07321332 250 mg (tablet) under fasted condition in period 2, and PF-07321332 250 mg (tablet) under fed condition in period 3. There was a washout interval of at least 2 days between dosing in each period. | 4 |
| PART-3: rBA/FE Treatment Sequence 2 PF-07321332 250 mg (Tablet), Fasted=\>PF-07321332 250 mg (Tablet), Fed=\>PF-07321332 250 mg (Suspension), Fasted Participants received a single dose of PF-07321332 250 mg (tablet) under fasted condition in period 1, PF-07321332 250 mg (tablet) under fed condition in period 2, and PF-07321332 250 mg (suspension) under fasted condition in period 3. There was a washout interval of at least 2 days between dosing in each period. | 4 |
| PART-3: rBA/FE Treatment Sequence 3 PF-07321332 250 mg (Tablet), Fed=\>PF-07321332 250 mg (Suspension), Fasted=\>PF-07321332 250 mg (Tablet), Fasted Participants received a single dose of PF-07321332 250 mg (tablet) under fed condition in period 1, PF-07321332 250 mg (suspension) under fasted condition in period 2, and PF-07321332 250 mg (tablet) under fasted condition in period 3. There was a washout interval of at least 2 days between dosing in each period. | 4 |
| PART-4: M&E PF-07321332 300 mg (Suspension)/RTV 100 mg, Fasted Participants received a single oral dose of PF-07321332 300 mg with RTV (4 doses of 100 mg at -12h, 0h, 12h, and 24h relative to PF-07321332) under fasted condition. | 6 |
| PART-5: SE Placebo (Suspension)/RTV 100 mg=>PF-07321332 2250 mg (Suspension)/RTV 100 mg In period 1, participants received placebo (3 split doses at 0, 2h, and 4h) with RTV (3 doses of 100 mg at -12h, 0h and 12h post-dose) approximately 2h after breakfast. In period 2, participants received PF-07321332 2250 mg (divided into 3 doses of 750 mg administered at 0, 2h, and 4h) with RTV (3 doses of 100 mg at -12h, 0h and 12h post-dose) approximately 2h after breakfast. There was a washout interval of ≥5 days between periods. | 5 |
| PART-5: SE PF-07321332 2250 mg (Suspension)/RTV 100 mg=>Placebo (Suspension)/RTV 100 mg In period 1, participants received PF-07321332 2250 mg (divided into 3 doses of 750 mg administered at 0, 2h, and 4h) with RTV (3 doses of 100 mg at -12h, 0h and 12h post-dose) approximately 2h after breakfast. In period 2, participants received placebo (3 split doses at 0, 2h, and 4h) with RTV (3 doses of 100 mg at -12h, 0h and 12h post-dose) approximately 2h after breakfast. There was a washout interval of ≥5 days between periods. | 5 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | PART-1: SAD Treatment Sequence 2 | PART-1:SAD Treatment Sequence 3 | PART-1: SAD Treatment Sequence 4 | PART-1: SAD Treatment Sequence 5 | PART-1: SAD Treatment Sequence 6 | PART-2: MAD Placebo (Suspension)/RTV 100 mg Twice Daily (BID), Fasted | PART-2: MAD PF-07321332 (Suspension)/RTV 75/100 mg BID, Fasted | PART-2: MAD PF-07321332 (Suspension)/RTV 250/100 mg BID, Fasted | PART-2: MAD PF-07321332 (Suspension)/RTV 500/100 mg BID, Fasted | PART-2: MAD Placebo (Suspension)/RTV100 mg BID, Fasted, Japanese | PART-2: MAD PF-07321332 (Suspension)/RTV 250/100 mg BID, Fasted, Japanese | PART-3: rBA/FE Treatment Sequence 1 | PART-3: rBA/FE Treatment Sequence 2 | PART-3: rBA/FE Treatment Sequence 3 | PART-4: M&E PF-07321332 300 mg (Suspension)/RTV 100 mg, Fasted | PART-5: SE Placebo (Suspension)/RTV 100 mg=>PF-07321332 2250 mg (Suspension)/RTV 100 mg | PART-1: SAD Treatment Sequence 1 | PART-5: SE PF-07321332 2250 mg (Suspension)/RTV 100 mg=>Placebo (Suspension)/RTV 100 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 Years | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants | 3 Participants | 2 Participants | 5 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 44 Participants |
| Age, Customized 45-60 Years | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 26 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 11 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 5 Participants | 4 Participants | 3 Participants | 7 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 5 Participants | 1 Participants | 4 Participants | 59 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 6 Participants | 3 Participants | 2 Participants | 6 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 6 Participants | 4 Participants | 0 Participants | 3 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 4 | 0 / 7 | 0 / 2 | 0 / 4 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 6 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 2 / 6 | 1 / 4 | 1 / 2 | 0 / 4 | 1 / 4 | 1 / 4 | 1 / 4 | 0 / 4 | 0 / 4 | 4 / 8 | 3 / 4 | 3 / 4 | 4 / 7 | 2 / 2 | 4 / 4 | 3 / 12 | 3 / 12 | 1 / 12 | 1 / 6 | 3 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 | 0 / 2 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 4 | 0 / 7 | 0 / 2 | 0 / 4 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 6 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Tablet Formulation and Suspension in PART-3: rBA/FE
AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. Natural log transformed AUCinf for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet\] /Reference \[suspension\]) and 90% CI for the ratio.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Tablet Formulation and Suspension in PART-3: rBA/FE | 3513 ng*hr/ml | Geometric Coefficient of Variation 38 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Tablet Formulation and Suspension in PART-3: rBA/FE | 2958 ng*hr/ml | Geometric Coefficient of Variation 50 |
90% CI: [60.14, 96.2]
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Tablet Formulation and Suspension in PART-3: rBA/FE
AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Area Under the Plasma Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Tablet Formulation and Suspension in PART-3: rBA/FE | 3318 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Area Under the Plasma Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Tablet Formulation and Suspension in PART-3: rBA/FE | 2695 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 46 |
90% CI: [69.21, 95.28]
Primary
Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE
Cmax is maximum plasma concentration. It was observed directly from data. Natural log transformed Cmax for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet\] /Reference \[suspension\]) and 90% CI for the ratio.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE | 883.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE | 497.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
90% CI: [43.42, 73.19]
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD
Vital signs (temperature, respiratory rate, pulse rate \[PR\], systolic blood pressure \[SBP\], and diastolic blood pressure \[DBP\]) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 millimeters of mercury (mm Hg), increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 beats per minute (bpm) or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of study intervention and had at least 1 assessment undertaken post treatment.
Time frame: Baseline up to Day 2 of the final period
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 2 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 1 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 1 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 1 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 1 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP decrease >=30 mmHg | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | SBP value <90 mmHg | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD | DBP decrease >=20 mmHg | 0 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD
Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 mm Hg, increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 bpm or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion.
Time frame: Baseline up to Day 12
Population: The analysis population included all participants who received at least 1 dose of study intervention and had at least 1 assessment undertaken post treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | DBP value <50 mmHg | 1 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP decrease >=30 mmHg | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP value <90 mmHg | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | PR value <40 bpm | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | DBP value <50 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP value <90 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | PR value <40 bpm | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP decrease >=30 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP value <90 mmHg | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | PR value <40 bpm | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP decrease >=30 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | DBP value <50 mmHg | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP decrease >=30 mmHg | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | PR value <40 bpm | 1 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP value <90 mmHg | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | DBP value <50 mmHg | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP decrease >=30 mmHg | 1 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | PR value <40 bpm | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP value <90 mmHg | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | DBP value <50 mmHg | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP decrease >=30 mmHg | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | PR value <40 bpm | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | DBP value <50 mmHg | 1 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD | SBP value <90 mmHg | 1 Participants |
Primary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE
Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value \<50 mm Hg, increase \>=20 mm Hg, or decrease \>=20 mm Hg; PR: value \<40 bpm or value \>120 bpm; SBP: value \<90 mm Hg, increase \>=30 mm Hg, or decrease \>=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion.
Time frame: Baseline up to Day 5 of the final period
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE | SBP value <90 mmHg | 1 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE | SBP decrease >= 30 mmHg | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE | SBP value <90 mmHg | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE | SBP decrease >= 30 mmHg | 1 Participants |
Primary
Number of Participants With Laboratory Abnormalities in PART-1: SAD
Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, Severe Acute Respiratory Syndrome Coronavirus 2 \[SARS-CoV-2\] reverse transcription polymerase chain reaction \[RT-PCR\], estimated glomerular filtration rate \[eGFR\], pregnancy test \[beta human chorionic gonadotropin \[b-hCG\]\], activated partial thromboplastin time \[aPTT\], prothrombin time \[PT\] - international normalized ratio \[INR\], fibrinogen, thyroid stimulating hormone \[TSH\], Free thyroxine \[T4\]). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.
Time frame: Baseline up to Day 4 of the final period
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 2 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 1 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 2 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 1 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 1 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 1 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Laboratory Abnormalities in PART-1: SAD | 2 Participants |
Primary
Number of Participants With Laboratory Abnormalities in PART-2: MAD
Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.
Time frame: Baseline up to Day 12
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-2: MAD | 5 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Laboratory Abnormalities in PART-2: MAD | 2 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Laboratory Abnormalities in PART-2: MAD | 4 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-2: MAD | 5 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-2: MAD | 2 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-2: MAD | 3 Participants |
Primary
Number of Participants With Laboratory Abnormalities in PART-5: SE
Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.
Time frame: Baseline up to Day 5 of the final period
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-5: SE | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Laboratory Abnormalities in PART-5: SE | 2 Participants |
Primary
Number of Participants With TEAEs in PART-2:MAD
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.
Time frame: Post first dose till up to 45 days after last dose of study intervention
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality TEAEs | 4 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with severe AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with treatment-related TEAEs | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality TEAEs | 3 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with treatment-related TEAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-2:MAD | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-2:MAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-2:MAD | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-2:MAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-2:MAD | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-2:MAD | Participants with treatment-related TEAEs | 2 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-2:MAD | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality TEAEs | 3 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with severe AEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with treatment-related TEAEs | 2 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality TEAEs | 4 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with severe AEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality TEAEs | 2 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with treatment-related TEAEs | 1 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality TEAEs | 4 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with severe AEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Participants with treatment-related TEAEs | 2 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With TEAEs in PART-2:MAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
Primary
Number of Participants With TEAEs in PART-5: SE
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.
Time frame: Post first dose till up to 36 days after last dose of study intervention
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with treatment-related TEAEs | 1 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-5: SE | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-5: SE | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-5: SE | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with all-causality TEAEs | 3 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-5: SE | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with all-causality TEAEs | 3 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with treatment-related TEAEs | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-5: SE | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-5: SE | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-5: SE | Discontinued study drug due to AE, study continued | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD
An Adverse Event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. 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 significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.
Time frame: Post the single dose of study intervention till up to 36 days
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 2 Participants |
| Placebo (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 150 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 1 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 1 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 1 Participants |
| PF-07321332 1500 mg (Suspension), Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 1 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 250 mg (Suspension)/RTV 100 mg, Fed | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality SAEs | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants discontinued from study due to AEs | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with treatment-related TEAEs | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Discontinued study drug due to AE, study continued | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with all-causality TEAEs | 0 Participants |
| PF-07321332 750 mg (Suspension)/RTV 100 mg, Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD | Participants with severe AEs | 0 Participants |
Primary
Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME
Total recovery of drug-related material excreted in urine and feces combined, expressed as a percent of total dose administered, measured by 19F-NMR.
Time frame: Day 1 to Day 11
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME | PF-07321332-related material by 19F-NMR | 80.7 Percent of the dose | Standard Deviation 8 |
| Placebo (Suspension), Fasted | Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME | M8 (PF-07331782) | 4.2 Percent of the dose | Standard Deviation 1.3 |
| Placebo (Suspension), Fasted | Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME | Total | 84.9 Percent of the dose | Standard Deviation 8.9 |
Primary
Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME
Total recovery of drug-related material excreted in feces, expressed as a percent of total dose administered, measured by 19F-NMR.
Time frame: Day 1 to Day 11
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME | PF-07321332-related material by 19F-NMR | 33.7 Percent of the dose | Standard Deviation 13.3 |
| Placebo (Suspension), Fasted | Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME | M8 (PF-07331782) | 1.6 Percent of the dose | Standard Deviation 0.6 |
Primary
Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME
Total recovery of drug-related material excreted in urine, expressed as a percent of total dose administered, measured by fluorine-19 nuclear magnetic resonance (19F-NMR).
Time frame: Day 1 to Day 11
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME | PF-07321332-related material by 19F-NMR | 47.0 Percent of the dose | Standard Deviation 10.3 |
| Placebo (Suspension), Fasted | Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME | M8 (PF-07331782) | 2.6 Percent of the dose | Standard Deviation 1.1 |
Secondary
Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10
Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Aetau is the sum of (urine volume × urine concentration) for each collection over the dosing interval.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10 | 47.83 mg | Geometric Coefficient of Variation 12 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10 | 129.9 mg | Geometric Coefficient of Variation 4 |
| Placebo (Suspension)/RTV 100 mg, Fed | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10 | 116.5 mg | Geometric Coefficient of Variation 122 |
| PF-07321332 150 mg (Suspension), Fasted | Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10 | 135.4 mg | Geometric Coefficient of Variation 5 |
Secondary
Apparent Clearance (CL/F) in PART-1: SAD
CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Apparent Clearance (CL/F) in PART-1: SAD | 66.83 liter/hour (L/hr) | Geometric Coefficient of Variation 43 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Apparent Clearance (CL/F) in PART-1: SAD | NA liter/hour (L/hr) | — |
| PF-07321332 150 mg (Suspension), Fasted | Apparent Clearance (CL/F) in PART-1: SAD | 8.865 liter/hour (L/hr) | Geometric Coefficient of Variation 14 |
| PF-07321332 500 mg (Suspension), Fasted | Apparent Clearance (CL/F) in PART-1: SAD | 8.735 liter/hour (L/hr) | Geometric Coefficient of Variation 17 |
| PF-07321332 1500 mg (Suspension), Fasted | Apparent Clearance (CL/F) in PART-1: SAD | 11.22 liter/hour (L/hr) | Geometric Coefficient of Variation 45 |
Secondary
Apparent Volume of Distribution (Vz/F) in PART-1: SAD
Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Apparent Volume of Distribution (Vz/F) in PART-1: SAD | 190.6 Liter | Geometric Coefficient of Variation 36 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Apparent Volume of Distribution (Vz/F) in PART-1: SAD | NA Liter | — |
| PF-07321332 150 mg (Suspension), Fasted | Apparent Volume of Distribution (Vz/F) in PART-1: SAD | 87.98 Liter | Geometric Coefficient of Variation 28 |
| PF-07321332 500 mg (Suspension), Fasted | Apparent Volume of Distribution (Vz/F) in PART-1: SAD | 73.48 Liter | Geometric Coefficient of Variation 47 |
| PF-07321332 1500 mg (Suspension), Fasted | Apparent Volume of Distribution (Vz/F) in PART-1: SAD | 181.9 Liter | Geometric Coefficient of Variation 35 |
Secondary
Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
AUCtau is area under the concentration-time profile from time 0 (pre-dose) to end of dosing interval, where dosing interval was 12 hours.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 12570 ng*hr/mL | Geometric Coefficient of Variation 17 |
| Placebo (Suspension), Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 6017 ng*hr/mL | Geometric Coefficient of Variation 33 |
| Placebo (Suspension), Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 12650 ng*hr/mL | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 35560 ng*hr/mL | Geometric Coefficient of Variation 26 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 37780 ng*hr/mL | Geometric Coefficient of Variation 27 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 18700 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Placebo (Suspension)/RTV 100 mg, Fed | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 39780 ng*hr/mL | Geometric Coefficient of Variation 20 |
| Placebo (Suspension)/RTV 100 mg, Fed | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 38150 ng*hr/mL | Geometric Coefficient of Variation 23 |
| Placebo (Suspension)/RTV 100 mg, Fed | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 22610 ng*hr/mL | Geometric Coefficient of Variation 37 |
| PF-07321332 150 mg (Suspension), Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 13130 ng*hr/mL | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 25480 ng*hr/mL | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 26930 ng*hr/mL | Geometric Coefficient of Variation 15 |
Secondary
AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE
AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 14.06 ng*hr/mL/mg | Geometric Coefficient of Variation 38 |
| Placebo (Suspension)/RTV 100 mg, Fasted | AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 11.82 ng*hr/mL/mg | Geometric Coefficient of Variation 50 |
| Placebo (Suspension)/RTV 100 mg, Fed | AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 17.03 ng*hr/mL/mg | Geometric Coefficient of Variation 24 |
Secondary
AUCinf of PF-07321332 in PART-1: SAD
AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUCinf of PF-07321332 in PART-1: SAD | 2247 ng*hr/mL | Geometric Coefficient of Variation 42 |
| Placebo (Suspension)/RTV 100 mg, Fasted | AUCinf of PF-07321332 in PART-1: SAD | NA ng*hr/mL | — |
| PF-07321332 150 mg (Suspension), Fasted | AUCinf of PF-07321332 in PART-1: SAD | 28220 ng*hr/mL | Geometric Coefficient of Variation 14 |
| PF-07321332 500 mg (Suspension), Fasted | AUCinf of PF-07321332 in PART-1: SAD | 28640 ng*hr/mL | Geometric Coefficient of Variation 17 |
| PF-07321332 1500 mg (Suspension), Fasted | AUCinf of PF-07321332 in PART-1: SAD | 66760 ng*hr/mL | Geometric Coefficient of Variation 45 |
Secondary
AUCinf of Plasma PF-07321332 in PART-4: ME
AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUCinf of Plasma PF-07321332 in PART-4: ME | 33470 ng*hr/mL | Geometric Coefficient of Variation 22 |
Secondary
AUCinf of Plasma PF-07321332 in PART-5: SE
AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUCinf of Plasma PF-07321332 in PART-5: SE | 188800 ng*hr/ml | Geometric Coefficient of Variation 35 |
Secondary
AUCinf of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE
AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. Natural log transformed AUCinf for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet under fed condition\] /Reference \[tablet under fasted condition\]) and 90% CI for the ratio.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUCinf of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | 2958 ng*hr/mL | Geometric Coefficient of Variation 50 |
| Placebo (Suspension)/RTV 100 mg, Fasted | AUCinf of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | 4256 ng*hr/mL | Geometric Coefficient of Variation 24 |
90% CI: [118.8, 181.41]
Secondary
AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE
AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. AUClast(dn) = AUClast /dose.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 13.27 ng*hr/mL/mg | Geometric Coefficient of Variation 35 |
| Placebo (Suspension)/RTV 100 mg, Fasted | AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 10.78 ng*hr/mL/mg | Geometric Coefficient of Variation 46 |
| Placebo (Suspension)/RTV 100 mg, Fed | AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 16.03 ng*hr/mL/mg | Geometric Coefficient of Variation 27 |
Secondary
AUClast of Plasma PF-07321332 in PART-1: SAD
AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUClast of Plasma PF-07321332 in PART-1: SAD | 2125 ng*hr/mL | Geometric Coefficient of Variation 34 |
| Placebo (Suspension)/RTV 100 mg, Fasted | AUClast of Plasma PF-07321332 in PART-1: SAD | 3753 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Placebo (Suspension)/RTV 100 mg, Fed | AUClast of Plasma PF-07321332 in PART-1: SAD | 10870 ng*hr/mL | Geometric Coefficient of Variation 47 |
| PF-07321332 150 mg (Suspension), Fasted | AUClast of Plasma PF-07321332 in PART-1: SAD | 27600 ng*hr/mL | Geometric Coefficient of Variation 13 |
| PF-07321332 500 mg (Suspension), Fasted | AUClast of Plasma PF-07321332 in PART-1: SAD | 28020 ng*hr/mL | Geometric Coefficient of Variation 16 |
| PF-07321332 1500 mg (Suspension), Fasted | AUClast of Plasma PF-07321332 in PART-1: SAD | 64230 ng*hr/mL | Geometric Coefficient of Variation 39 |
Secondary
AUClast of Plasma PF-07321332 in PART-4: ME
AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUClast of Plasma PF-07321332 in PART-4: ME | 32960 ng*hr/mL | Geometric Coefficient of Variation 23 |
Secondary
AUClast of Plasma PF-07321332 in PART-5: SE
AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUClast of Plasma PF-07321332 in PART-5: SE | 188200 ng*hr/ml | Geometric Coefficient of Variation 35 |
Secondary
AUClast of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE
AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. Natural log transformed AUClast for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet under fed condition\] /Reference \[tablet under fasted condition\]) and 90% CI for the ratio.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | AUClast of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | 2695 ng*hr/mL | Geometric Coefficient of Variation 46 |
| Placebo (Suspension)/RTV 100 mg, Fasted | AUClast of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | 4012 ng*hr/mL | Geometric Coefficient of Variation 27 |
90% CI: [126.92, 174.72]
Secondary
Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
Cav is average plasma concentration over the dosing interval, where dosing interval was 12 hours.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1049 ng/mL | Geometric Coefficient of Variation 17 |
| Placebo (Suspension), Fasted | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 1053 ng/mL | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 3147 ng/mL | Geometric Coefficient of Variation 27 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 2963 ng/mL | Geometric Coefficient of Variation 26 |
| Placebo (Suspension)/RTV 100 mg, Fed | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 3314 ng/mL | Geometric Coefficient of Variation 20 |
| Placebo (Suspension)/RTV 100 mg, Fed | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 3181 ng/mL | Geometric Coefficient of Variation 23 |
| PF-07321332 150 mg (Suspension), Fasted | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 2124 ng/mL | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 2245 ng/mL | Geometric Coefficient of Variation 14 |
Secondary
CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10
CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCtau.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 5 | 5.966 L/hr | Geometric Coefficient of Variation 17 |
| Placebo (Suspension), Fasted | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 10 | 5.933 L/hr | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fasted | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 10 | 6.617 L/hr | Geometric Coefficient of Variation 27 |
| Placebo (Suspension)/RTV 100 mg, Fasted | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 5 | 7.032 L/hr | Geometric Coefficient of Variation 26 |
| Placebo (Suspension)/RTV 100 mg, Fed | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 5 | 13.11 L/hr | Geometric Coefficient of Variation 23 |
| Placebo (Suspension)/RTV 100 mg, Fed | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 10 | 12.57 L/hr | Geometric Coefficient of Variation 20 |
| PF-07321332 150 mg (Suspension), Fasted | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 5 | 9.814 L/hr | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10 | Day 10 | 9.278 L/hr | Geometric Coefficient of Variation 15 |
Secondary
CL/F of Plasma PF-07321332 in PART-3: rBA/FE
CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | CL/F of Plasma PF-07321332 in PART-3: rBA/FE | 71.07 L/hr | Geometric Coefficient of Variation 38 |
| Placebo (Suspension)/RTV 100 mg, Fasted | CL/F of Plasma PF-07321332 in PART-3: rBA/FE | 84.56 L/hr | Geometric Coefficient of Variation 50 |
| Placebo (Suspension)/RTV 100 mg, Fed | CL/F of Plasma PF-07321332 in PART-3: rBA/FE | 58.70 L/hr | Geometric Coefficient of Variation 24 |
Secondary
CL/F of Plasma PF-07321332 in PART-4: ME
CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | CL/F of Plasma PF-07321332 in PART-4: ME | 8.968 L/hr | Geometric Coefficient of Variation 22 |
Secondary
Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 13.89 ng/mL/mg | Geometric Coefficient of Variation 28 |
| Placebo (Suspension), Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 27.40 ng/mL/mg | Geometric Coefficient of Variation 14 |
| Placebo (Suspension), Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 29.66 ng/mL/mg | Geometric Coefficient of Variation 27 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 9.755 ng/mL/mg | Geometric Coefficient of Variation 36 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 20.49 ng/mL/mg | Geometric Coefficient of Variation 25 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 19.10 ng/mL/mg | Geometric Coefficient of Variation 21 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 10.59 ng/mL/mg | Geometric Coefficient of Variation 21 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 6.103 ng/mL/mg | Geometric Coefficient of Variation 32 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 11.22 ng/mL/mg | Geometric Coefficient of Variation 17 |
| PF-07321332 150 mg (Suspension), Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 7.698 ng/mL/mg | Geometric Coefficient of Variation 25 |
| PF-07321332 150 mg (Suspension), Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 15.08 ng/mL/mg | Geometric Coefficient of Variation 21 |
| PF-07321332 150 mg (Suspension), Fasted | Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 14.70 ng/mL/mg | Geometric Coefficient of Variation 28 |
Secondary
Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE
Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 3.533 ng/mL/mg | Geometric Coefficient of Variation 37 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 1.992 ng/mL/mg | Geometric Coefficient of Variation 37 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE | 4.874 ng/mL/mg | Geometric Coefficient of Variation 55 |
Secondary
Cmax of Plasma PF-07321332 in PART-1: SAD
Cmax is maximum plasma concentration. It was observed directly from data.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-1: SAD | 667.7 ng/mL | Geometric Coefficient of Variation 28 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax of Plasma PF-07321332 in PART-1: SAD | 674.4 ng/mL | Geometric Coefficient of Variation 38 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax of Plasma PF-07321332 in PART-1: SAD | 1538 ng/mL | Geometric Coefficient of Variation 32 |
| PF-07321332 150 mg (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-1: SAD | 2882 ng/mL | Geometric Coefficient of Variation 25 |
| PF-07321332 500 mg (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-1: SAD | 3323 ng/mL | Geometric Coefficient of Variation 13 |
| PF-07321332 1500 mg (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-1: SAD | 5086 ng/mL | Geometric Coefficient of Variation 25 |
Secondary
Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
Cmax is maximum plasma concentration. It was observed directly from data.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 1042 ng/mL | Geometric Coefficient of Variation 28 |
| Placebo (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 2055 ng/mL | Geometric Coefficient of Variation 14 |
| Placebo (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 2224 ng/mL | Geometric Coefficient of Variation 27 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 2435 ng/mL | Geometric Coefficient of Variation 36 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 5123 ng/mL | Geometric Coefficient of Variation 24 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 4774 ng/mL | Geometric Coefficient of Variation 21 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 5296 ng/mL | Geometric Coefficient of Variation 21 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 3051 ng/mL | Geometric Coefficient of Variation 32 |
| Placebo (Suspension)/RTV 100 mg, Fed | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 5607 ng/mL | Geometric Coefficient of Variation 17 |
| PF-07321332 150 mg (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 1925 ng/mL | Geometric Coefficient of Variation 25 |
| PF-07321332 150 mg (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 3772 ng/mL | Geometric Coefficient of Variation 21 |
| PF-07321332 150 mg (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 3674 ng/mL | Geometric Coefficient of Variation 28 |
Secondary
Cmax of Plasma PF-07321332 in PART-4: ME
Cmax is maximum plasma concentration. It was observed directly from data.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-4: ME | 4068 ng/mL | Geometric Coefficient of Variation 14 |
Secondary
Cmax of Plasma PF-07321332 in PART-5: SE
Cmax is maximum plasma concentration. It was observed directly from data.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Cmax of Plasma PF-07321332 in PART-5: SE | 15940 ng/mL | Geometric Coefficient of Variation 27 |
Secondary
Cmax of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE
Cmax is maximum plasma concentration. It was observed directly from data. Natural log transformed Cmax for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test \[tablet under fed condition\] /Reference \[tablet under fasted condition\]) and 90% CI for the ratio.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Cmax of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | 497.8 ng/mL | Geometric Coefficient of Variation 37 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Cmax of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE | 1219 ng/mL | Geometric Coefficient of Variation 55 |
90% CI: [188.58, 317.87]
Secondary
Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD
AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD | 14.97 ng*hr/mL/mg | Geometric Coefficient of Variation 42 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD | NA ng*hr/mL/mg | — |
| PF-07321332 150 mg (Suspension), Fasted | Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD | 112.8 ng*hr/mL/mg | Geometric Coefficient of Variation 14 |
| PF-07321332 500 mg (Suspension), Fasted | Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD | 114.2 ng*hr/mL/mg | Geometric Coefficient of Variation 17 |
| PF-07321332 1500 mg (Suspension), Fasted | Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD | 89.14 ng*hr/mL/mg | Geometric Coefficient of Variation 45 |
Secondary
Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD
AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. AUClast(dn) = AUClast /dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD | 14.15 ng*hr/mL/mg | Geometric Coefficient of Variation 34 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD | 7.507 ng*hr/mL/mg | Geometric Coefficient of Variation 29 |
| Placebo (Suspension)/RTV 100 mg, Fed | Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD | 7.247 ng*hr/mL/mg | Geometric Coefficient of Variation 47 |
| PF-07321332 150 mg (Suspension), Fasted | Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD | 110.4 ng*hr/mL/mg | Geometric Coefficient of Variation 13 |
| PF-07321332 500 mg (Suspension), Fasted | Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD | 112.0 ng*hr/mL/mg | Geometric Coefficient of Variation 16 |
| PF-07321332 1500 mg (Suspension), Fasted | Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD | 85.77 ng*hr/mL/mg | Geometric Coefficient of Variation 40 |
Secondary
Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
AUCtau is area under the concentration-time profile from time 0 (pre-dose) to end of dosing interval, where dosing interval was 12 hours. AUCtau(dn) = AUCtau/dose.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 167.7 ng*hr/mL/mg | Geometric Coefficient of Variation 17 |
| Placebo (Suspension), Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 80.19 ng*hr/mL/mg | Geometric Coefficient of Variation 33 |
| Placebo (Suspension), Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 168.3 ng*hr/mL/mg | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 151.1 ng*hr/mL/mg | Geometric Coefficient of Variation 26 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 74.76 ng*hr/mL/mg | Geometric Coefficient of Variation 43 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 141.9 ng*hr/mL/mg | Geometric Coefficient of Variation 26 |
| Placebo (Suspension)/RTV 100 mg, Fed | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 79.56 ng*hr/mL/mg | Geometric Coefficient of Variation 20 |
| Placebo (Suspension)/RTV 100 mg, Fed | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 45.23 ng*hr/mL/mg | Geometric Coefficient of Variation 37 |
| Placebo (Suspension)/RTV 100 mg, Fed | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 76.32 ng*hr/mL/mg | Geometric Coefficient of Variation 23 |
| PF-07321332 150 mg (Suspension), Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 102.0 ng*hr/mL/mg | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 52.60 ng*hr/mL/mg | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 107.7 ng*hr/mL/mg | Geometric Coefficient of Variation 15 |
Secondary
Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD
Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD | 4.450 ng/mL/mg | Geometric Coefficient of Variation 28 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD | 1.349 ng/mL/mg | Geometric Coefficient of Variation 38 |
| Placebo (Suspension)/RTV 100 mg, Fed | Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD | 1.025 ng/mL/mg | Geometric Coefficient of Variation 32 |
| PF-07321332 150 mg (Suspension), Fasted | Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD | 11.53 ng/mL/mg | Geometric Coefficient of Variation 25 |
| PF-07321332 500 mg (Suspension), Fasted | Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD | 13.32 ng/mL/mg | Geometric Coefficient of Variation 13 |
| PF-07321332 1500 mg (Suspension), Fasted | Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD | 6.782 ng/mL/mg | Geometric Coefficient of Variation 25 |
Secondary
Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
Cmin is minimum observed concentration during the dosing interval, where dosing interval was 12 hours.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 245.3 ng/mL | Geometric Coefficient of Variation 27 |
| Placebo (Suspension), Fasted | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 251.0 ng/mL | Geometric Coefficient of Variation 11 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1315 ng/mL | Geometric Coefficient of Variation 37 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 1480 ng/mL | Geometric Coefficient of Variation 27 |
| Placebo (Suspension)/RTV 100 mg, Fed | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1195 ng/mL | Geometric Coefficient of Variation 29 |
| Placebo (Suspension)/RTV 100 mg, Fed | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 1279 ng/mL | Geometric Coefficient of Variation 31 |
| PF-07321332 150 mg (Suspension), Fasted | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 12.50 ng/mL | — |
| PF-07321332 150 mg (Suspension), Fasted | Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 707.3 ng/mL | Geometric Coefficient of Variation 35 |
Secondary
Number of Participants With Laboratory Abnormalities in PART-4: ME
Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion.
Time frame: Baseline up to Day 11
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Laboratory Abnormalities in PART-4: ME | 3 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE
Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test \[b-hCG\], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.
Time frame: Baseline up to Day 3
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE | 2 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE | 0 Participants |
Secondary
Number of Participants With TEAEs in PART-3: rBA/FE
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.
Time frame: Post the single dose of study intervention till up to 36 days
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with all-causality TEAEs | 3 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with treatment-related TEAEs | 2 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with severe AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with all-causality TEAEs | 3 Participants |
| Placebo (Suspension)/RTV 100 mg, Fasted | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with treatment-related TEAEs | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with treatment-related TEAEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with severe AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-3: rBA/FE | Participants with all-causality TEAEs | 1 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-3: rBA/FE | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-3: rBA/FE | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension)/RTV 100 mg, Fed | Number of Participants With TEAEs in PART-3: rBA/FE | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
Secondary
Number of Participants With TEAEs in PART-4: ME
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An 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. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.
Time frame: Post the single dose of study intervention till up to 36 days
Population: The analysis population included all participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-4: ME | Participants with all-causality TEAEs | 1 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-4: ME | Participants with treatment-related TEAEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-4: ME | Participants with all-causality SAEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-4: ME | Participants with severe AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-4: ME | Participants discontinued from study due to AEs | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-4: ME | Discontinued study drug due to AE, study continued | 0 Participants |
| Placebo (Suspension), Fasted | Number of Participants With TEAEs in PART-4: ME | Dose reduced/temporary discontinuation due to AEs | 0 Participants |
Secondary
Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
Rac was calculated as Day 5 or Day 10 AUCtau/Day 1 AUCtau.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 2.091 Ratio | Geometric Coefficient of Variation 24 |
| Placebo (Suspension), Fasted | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 2.104 Ratio | Geometric Coefficient of Variation 30 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 2.022 Ratio | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1.901 Ratio | Geometric Coefficient of Variation 22 |
| Placebo (Suspension)/RTV 100 mg, Fed | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1.685 Ratio | Geometric Coefficient of Variation 29 |
| Placebo (Suspension)/RTV 100 mg, Fed | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 1.757 Ratio | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1.937 Ratio | Geometric Coefficient of Variation 18 |
| PF-07321332 150 mg (Suspension), Fasted | Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 2.047 Ratio | Geometric Coefficient of Variation 16 |
Secondary
Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
Rac,Cmax is Day 5 or Day 10 Cmax/Day 1 Cmax.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 1.971 Ratio | Geometric Coefficient of Variation 34 |
| Placebo (Suspension), Fasted | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 2.133 Ratio | Geometric Coefficient of Variation 25 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 2.101 Ratio | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1.959 Ratio | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fed | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1.733 Ratio | Geometric Coefficient of Variation 24 |
| Placebo (Suspension)/RTV 100 mg, Fed | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 1.840 Ratio | Geometric Coefficient of Variation 29 |
| PF-07321332 150 mg (Suspension), Fasted | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 1.909 Ratio | Geometric Coefficient of Variation 26 |
| PF-07321332 150 mg (Suspension), Fasted | Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 1.962 Ratio | Geometric Coefficient of Variation 14 |
Secondary
Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10
PTR is defined as peak-to-trough ratio. PTR = Cmax/Cmin.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 8.857 Ratio | Geometric Coefficient of Variation 27 |
| Placebo (Suspension), Fasted | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 8.383 Ratio | Geometric Coefficient of Variation 16 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 3.462 Ratio | Geometric Coefficient of Variation 5 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 3.635 Ratio | Geometric Coefficient of Variation 21 |
| Placebo (Suspension)/RTV 100 mg, Fed | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 4.430 Ratio | Geometric Coefficient of Variation 14 |
| Placebo (Suspension)/RTV 100 mg, Fed | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 4.385 Ratio | Geometric Coefficient of Variation 17 |
| PF-07321332 150 mg (Suspension), Fasted | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 5 | 5.194 Ratio | Geometric Coefficient of Variation 19 |
| PF-07321332 150 mg (Suspension), Fasted | Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10 | Day 10 | 6.270 Ratio | Geometric Coefficient of Variation 32 |
Secondary
Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10
Aetau% is defined as percent of dose excreted in urine as unchanged drug over the dosing interval, where the dosing interval is 12 hours. Aetau% = Aetau / Dose \* 100.
Time frame: Pre-dose to 12 hours post-dose on Day 10
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10 | 63.79 percentage of dose | Geometric Coefficient of Variation 12 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10 | 51.81 percentage of dose | Geometric Coefficient of Variation 4 |
| Placebo (Suspension)/RTV 100 mg, Fed | Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10 | 23.35 percentage of dose | Geometric Coefficient of Variation 121 |
| PF-07321332 150 mg (Suspension), Fasted | Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10 | 54.20 percentage of dose | Geometric Coefficient of Variation 5 |
Secondary
Renal Clearance (CLr) in PART-2: MAD on Day 10
CLr is defined as the renal clearance. CLr = Aetau / AUCtau, where the dosing interval was 12 hours.
Time frame: Pre-dose to 12 hours post-dose on Day 10
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Renal Clearance (CLr) in PART-2: MAD on Day 10 | 3.782 L/hr | Geometric Coefficient of Variation 20 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Renal Clearance (CLr) in PART-2: MAD on Day 10 | 3.433 L/hr | Geometric Coefficient of Variation 23 |
| Placebo (Suspension)/RTV 100 mg, Fed | Renal Clearance (CLr) in PART-2: MAD on Day 10 | 2.934 L/hr | Geometric Coefficient of Variation 128 |
| PF-07321332 150 mg (Suspension), Fasted | Renal Clearance (CLr) in PART-2: MAD on Day 10 | 5.028 L/hr | Geometric Coefficient of Variation 11 |
Secondary
t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10
t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10 | 7.955 hr | Standard Deviation 2.0401 |
| Placebo (Suspension)/RTV 100 mg, Fasted | t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10 | 6.795 hr | Standard Deviation 1.7072 |
| Placebo (Suspension)/RTV 100 mg, Fed | t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10 | 8.047 hr | Standard Deviation 1.7871 |
| PF-07321332 150 mg (Suspension), Fasted | t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10 | 5.163 hr | Standard Deviation 2.0915 |
Secondary
t1/2 of Plasma PF-07321332 in PART-3: rBA/FE
t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | t1/2 of Plasma PF-07321332 in PART-3: rBA/FE | 5.626 hr | Standard Deviation 3.0407 |
| Placebo (Suspension)/RTV 100 mg, Fasted | t1/2 of Plasma PF-07321332 in PART-3: rBA/FE | 9.086 hr | Standard Deviation 4.157 |
| Placebo (Suspension)/RTV 100 mg, Fed | t1/2 of Plasma PF-07321332 in PART-3: rBA/FE | 1.854 hr | Standard Deviation 0.55166 |
Secondary
t1/2 of Plasma PF-07321332 in PART-4: ME
t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | t1/2 of Plasma PF-07321332 in PART-4: ME | 9.485 hr | Standard Deviation 3.1833 |
Secondary
t1/2 of Plasma PF-07321332 in PART-5: SE
t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | t1/2 of Plasma PF-07321332 in PART-5: SE | 7.450 hr | Standard Deviation 2.9357 |
Secondary
Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD
t1/2 is the time measured for the plasma concentration of drug to decrease by one half of its initial concentration.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD | 2.023 hr | Standard Deviation 0.54556 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD | NA hr | — |
| PF-07321332 150 mg (Suspension), Fasted | Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD | 6.935 hr | Standard Deviation 1.0794 |
| PF-07321332 500 mg (Suspension), Fasted | Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD | 6.005 hr | Standard Deviation 1.6502 |
| PF-07321332 1500 mg (Suspension), Fasted | Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD | 12.86 hr | Standard Deviation 8.4196 |
Secondary
Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD
Time to reach Cmax.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD | 0.634 hr |
| Placebo (Suspension)/RTV 100 mg, Fasted | Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD | 1.00 hr |
| Placebo (Suspension)/RTV 100 mg, Fed | Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD | 1.00 hr |
| PF-07321332 150 mg (Suspension), Fasted | Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD | 2.75 hr |
| PF-07321332 500 mg (Suspension), Fasted | Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD | 4.00 hr |
| PF-07321332 1500 mg (Suspension), Fasted | Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD | 2.00 hr |
Secondary
Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10
Time to reach Cmax.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 1.75 hr |
| Placebo (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 1.00 hr |
| Placebo (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 1.00 hr |
| Placebo (Suspension)/RTV 100 mg, Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 1.50 hr |
| Placebo (Suspension)/RTV 100 mg, Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 1.00 hr |
| Placebo (Suspension)/RTV 100 mg, Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 0.750 hr |
| Placebo (Suspension)/RTV 100 mg, Fed | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 1.50 hr |
| Placebo (Suspension)/RTV 100 mg, Fed | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 2.00 hr |
| Placebo (Suspension)/RTV 100 mg, Fed | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 1.50 hr |
| PF-07321332 150 mg (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 1 | 2.75 hr |
| PF-07321332 150 mg (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 10 | 1.50 hr |
| PF-07321332 150 mg (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10 | Day 5 | 1.26 hr |
Secondary
Tmax of Plasma PF-07321332 in PART-3: rBA/FE
Time to reach Cmax.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-3: rBA/FE | 1.00 hr |
| Placebo (Suspension)/RTV 100 mg, Fasted | Tmax of Plasma PF-07321332 in PART-3: rBA/FE | 1.00 hr |
| Placebo (Suspension)/RTV 100 mg, Fed | Tmax of Plasma PF-07321332 in PART-3: rBA/FE | 1.75 hr |
Secondary
Tmax of Plasma PF-07321332 in PART-4: ME
Tmax is time to reach Cmax.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-4: ME | 2.00 hr |
Secondary
Tmax of Plasma PF-07321332 in PART-5: SE
Time to reach Cmax.
Time frame: Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Tmax of Plasma PF-07321332 in PART-5: SE | 5.00 hr |
Secondary
Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10
Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10 | 66.43 Liter | Geometric Coefficient of Variation 24 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10 | 63.40 Liter | Geometric Coefficient of Variation 13 |
| Placebo (Suspension)/RTV 100 mg, Fed | Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10 | 142.4 Liter | Geometric Coefficient of Variation 37 |
| PF-07321332 150 mg (Suspension), Fasted | Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10 | 65.04 Liter | Geometric Coefficient of Variation 31 |
Secondary
Vz/F of Plasma PF-07321332 in PART-3: rBA/FE
Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Vz/F of Plasma PF-07321332 in PART-3: rBA/FE | 493.7 Liter | Geometric Coefficient of Variation 63 |
| Placebo (Suspension)/RTV 100 mg, Fasted | Vz/F of Plasma PF-07321332 in PART-3: rBA/FE | 1004 Liter | Geometric Coefficient of Variation 41 |
| Placebo (Suspension)/RTV 100 mg, Fed | Vz/F of Plasma PF-07321332 in PART-3: rBA/FE | 151.0 Liter | Geometric Coefficient of Variation 36 |
Secondary
Vz/F of Plasma PF-07321332 in PART-4: ME
Vz/F = Dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Population: The analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Vz/F of Plasma PF-07321332 in PART-4: ME | 115.8 Liter | Geometric Coefficient of Variation 48 |