MedPath

A Study to Learn Safety and Blood Levels of PF-07817883 in Healthy People

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: Placebo
Registration Number
NCT05580003
Lead Sponsor
Pfizer
Brief Summary

The purpose of this clinical trial is to learn if the study medicine (called PF-07817883) is safe and how it goes in and out of the body in healthy people. PF-07817883 is for the potential treatment of COVID-19. Participants will take PF-07817883 by mouth up to 2 times a day. This study may also evaluate how much PF-07817883 gets into the body when taken as pill. We may study if people's diets can affect this study medicine. We may also examine how PF-07817883 is processed and removed by the human body. Finally, we may look into if PF-07817883 has potential to interact with midazolam.

Detailed Description

Combined 6-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: Drug-drug interaction with midazolam Part-6: Supratherapeutic exposure Part-1,2 and 6 are double blind, sponsor open and Part-3,4 and 5 are open label study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
94
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). A body weight of >45 kg may be considered in selected cases.
  • Japanese subjects who have four Japanese biologic grandparents born in Japan
  • Chinese participants who were born in mainland China and both parents are of the Chinese descent.
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
  • Use of prescription or nonprescription drugs and dietary and herbal supplements within 28 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Moxifloxacin 400 mg in PART-6 (open label)MoxifloxacinMoxifloxacin 400 mg at 0h followed by placebo at 1h
Placebo in PART-6PlaceboA single dose of placebo administered as divided doses (1h apart)
Moxifloxacin 400 mg in PART-6 (open label)PlaceboMoxifloxacin 400 mg at 0h followed by placebo at 1h
PF-07817883 DR3 in PART-2PF-07817883Optional dosing regimen
PF-07817883 DR4 in PART-2PF-07817883Optional dosing regimen
PF-07817883 in Japanese in PART-2PF-07817883Optional dosing regimen to be studied in Japanese population
PF-07817883 in Chinese in PART-2PF-07817883Optional dosing regimen to be studied in Chinese population
Placebo in PART-2Placebo-
PF-07817883 Dose 2 in PART-1PF-07817883-
PF-07817883 Dose 3 in PART-1PF-07817883-
PF-07817883 Dose 4 in PART-1PF-07817883-
PF-07817883 FORM-2 Fasted in PART-3PF-07817883Second solid oral formulations (FORM-2) is optional
PF-07817883 FORM-1 Fed in PART-3PF-07817883-
PF-07817883 Dose 6 in PART-1PF-07817883Optional dose levels
PF-07817883 DR2 in PART-2PF-07817883-
PF-07817883 Dose 1 in PART-1PF-07817883-
Placebo in PART-1PlaceboA single dose of placebo
PF-07817883 in PART-6PF-07817883A single dose at supratherapeutic exposure administered as divided doses (1h apart)
Midazolam 5 mg in PART-5MidazolamSingle dose of 5 mg alone
PF-07817883 FORM-2 Fed in PART-3PF-07817883-
PF-07817883 FORM-1 Fasted in PART-3PF-07817883First solid oral formulation (FORM1)
Midazolam 5 mg with PF-07817883 in PART-5PF-07817883Single dose of 5 mg on Day 10 with multiple doses (twice a day) of PF-07817883
PF-07817883 Dose 5 in PART-1PF-07817883Optional dose levels
PF-07817883 DR1 in PART-2PF-07817883DR=Dosing regimen; twice a day
PF-07817883 Suspension Fasted in PART-3PF-07817883PART-3 is optional
PF-07817883 in PART-4PF-07817883PART-4 is optional
Midazolam 5 mg with PF-07817883 in PART-5MidazolamSingle dose of 5 mg on Day 10 with multiple doses (twice a day) of PF-07817883
Primary Outcome Measures
NameTimeMethod
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

Part 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of MidazolamDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

AUCinf of midazolam was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.

Part 1: Number of Participants With Laboratory Test AbnormalitiesFrom start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)

Laboratory parameters included: (lymphocytes less than (\<) 0.8\*lower limit of normal \[LLN\] \[10\^3 per millimeter cube {mm3}\], lymphocytes/leukocytes \<0.8\*LLN \[percentage {%}\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], monocytes/leukocytes greater than (\>) 1.2\*upper limit of normal \[ULN\] \[%\], partial thromboplastin time \>1.1\*ULN \[seconds\]), chemistry (bicarbonate \<0.9\*LLN \[milliequivalents per liter {mEq/L}\], creatine kinase \>2.0\*ULN \[units per liter {U/L}\], lipase \>1.5\*ULN \[U/L\]), and urinalysis (urine hemoglobin greater than or equal to \[\>=\] 1, leukocyte esterase \>=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

Part 1: Number of Participants With Vital Signs Meeting Pre-Defined CriteriaUp to Day 2 of each period

Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value less than (\<) 90 millimeter of mercury (mmHg), change greater than or equal to (\>=) 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 beats per minute (bpm), value \> 120 bpm.

Part 1: Number of Participants With Electrocardiogram (ECG) AbnormalitiesUp to Day 2 of each period

Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.

Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

Part 2: Number of Participants With Laboratory Test AbnormalitiesFrom start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)

Laboratory parameters included: hematology (lymphocytes/leukocytes \>1.2\*ULN \[%\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], monocytes/leukocytes \>1.2\*ULN \[%\]), chemistry (urate \>1.2\*ULN \[milligrams per deciliter\] {mg/dL}), and urinalysis (ketones \>=1, urine hemoglobin \>=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

Part 2: Number of Participants With Vital Signs Meeting Pre-Defined CriteriaUp to Day 12

Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm. 4. Number of participants with vital signs meeting any of the pre-defined criteria is reported in this outcome measure.

Part 2: Number of Participants With Electrocardiogram (ECG) AbnormalitiesUp to Day 12

Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.

Part 3:Ratio Based on Area Under Plasma Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) and Area Under Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) of Oral Formulation and SuspensionDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Data for AUClast and AUCinf are reported in the descriptive section. AUClast was calculated by the linear/log trapezoidal method. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. Ratio based on AUClast and AUCinf of oral formulation and suspension were reported in statistical analysis.

Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and SuspensionDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Data for Cmax are reported in the descriptive section. Ratio based on Cmax of oral formulation and suspension were reported in statistical analysis.

Part 4: Percentage of Total Dose Administered Recovered in UrineUp to 144 hours post-dose

The percentage of total dose administered recovered in urine was reported in this outcome measure.

Part 4: Percentage of Total Dose Administered Recovered in FecesUp to 144 hours post-dose

The percentage of total dose administered recovered in feces was reported in this outcome measure.

Part 4: Percentage of Total Dose Administered Recovered in Urine and FecesUp to 144 hours post-dose

The percentage of total dose administered recovered in urine and feces was reported in this outcome measure.

Part 5: Maximum Observed Concentration (Cmax) of MidazolamDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

Cmax of midazolam was reported in this outcome measure.

Part 6: Number of Participants With TEAEsFrom start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

Part 6: Number of Participants With Laboratory Test AbnormalitiesFrom start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)

Laboratory parameters included: hematology (lymphocytes \<0.6\*LLN \[10\^3/mm3\], lymphocytes/leukocytes \>1.2\*ULN \[%\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], basophils/leukocytes \>1.2\*ULN \[%\], eosinophils/leukocytes \>1.2\*ULN \[%\], monocytes/leukocytes \>1.2\*ULN \[%\], partial thromboplastin time \>1.1\*ULN \[seconds\], prothrombin time \>1.1\*ULN \[seconds\]), chemistry (bicarbonate \<0.9\*LLN \[mEq/L\], creatine kinase \> 2.0\*ULN \[U/L\], lipase \> 1.5\*ULN \[U/L\], urobilinogen \>=1 \[ehrlich units/deciliter\] {EU/dL}) and urinalysis (urine hemoglobin \>=1, leukocyte esterase \>=1, ketones \>=1, bacteria \>20 \[per low power field\] {/lpf}). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

Part 6: Number of Participants With Vital Signs Meeting Pre-Defined CriteriaUp to Day 6 of each period

Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm.

Part 6: Number of Participants According to Categorization of ECG DataUp to Day 6 of each period

Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured QTcF interval, aggregate 450 milliseconds (msec) \< value \<= 480 msec and QTcF interval, aggregate 30 msec \< change \<= 60 msec. Number of participants with abnormalities in ECG were reported in this outcome measure.

Secondary Outcome Measures
NameTimeMethod
Part 3: Maximum Observed Concentration (Cmax) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Cmax of PF-07817883 was reported in this outcome measure.

Part 1: Maximum Observed Concentration (Cmax) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Cmax of PF-07817883 was reported in this outcome measure.

Part 1: Time for Cmax (Tmax) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Tmax of PF-07817883 was reported in this outcome measure.

Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.

Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Cmax(dn) of PF-07817883 was reported in this outcome measure. Cmax(dn) was calculated as Cmax/dose.

Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

AUClast(dn) of PF-07817883 was reported in this outcome measure. AUClast(dn) was calculated by AUClast/dose.

Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.

Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

AUCinf(dn) of PF-07817883 was reported in this outcome measure. AUCinf(dn) was calculated as AUCinf/dose.

Part 1: Terminal Half-Life (t1/2) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCinf\*kel).

Part 1: Apparent Clearance (CL/F) of PF-07817883Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.

Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Cmax of PF-07817883 was reported in this outcome measure.

Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Tmax of PF-07817883 was reported in this outcome measure.

Part 2: Area Under the Plasma Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval (AUCtau) of PF-07817883 on Days 1, 5 and 10Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)

AUCtau was defined as area under the plasma concentration-time profile from time 0 to time tau, the dosing interval, where tau= 12 hours. AUCtau of PF-07817883 was reported in this outcome measure. AUCtau was calculated by linear/log trapezoidal method.

Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 1012 hours on Day 5 and Day 10

C12 of PF-07817883 was reported in this outcome measure.

Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Cmax(dn) of PF-07817883 was reported in this outcome measure. Cmax(dn) was calculated as Cmax/dose.

Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)

AUCtau(dn) was defined as dose normalized AUCtau, where tau= 12 hours. AUCtau(dn) of PF-07817883 was reported in this outcome measure. AUCtau(dn) was calculated as AUCtau/dose.

Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)

Cav of PF-07817883 was reported in this outcome measure. Cav was calculated as AUCtau/12.

Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)

Rac was defined as observed accumulation ratio for AUCtau, where tau= 12 hours. Rac of PF-07817883 was reported in this outcome measure. Rac was calculated as AUCtau on Day 5 or Day 10/AUCtau on Day 1.

Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Rac,Cmax of PF-07817883 was reported in this outcome measure. Rac,Cmax was calculated as Cmax on Day 5 or Day 10/Cmax on Day 1.

Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

PTR of PF-07817883 was reported in this outcome measure. PTR was calculated as Cmax/Cmin.

Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.

Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau\*kel).

Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10Day 10 (0 to 12 hours)

Aetau was defined as amount excreted in urine as unchanged drug over the dosing interval tau, where tau= 12 hours. Aetau of PF-07817883 was reported in this outcome measure. Aetau was calculated as sum of (urine volume\*urine concentration) for each collection over the dosing interval.

Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10Day 10 (0 to 12 hours)

Aetau% was defined as percentage of dose excreted in urine as unchanged drug over the dosing interval tau, where tau= 12 hours. Aetau% of PF-07817883 was reported in this outcome measure. Aetau% was calculated as 100\*Aetau/dose.

Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10Day 10 (0 to 12 hours)

CLr of PF-07817883 was reported in this outcome measure. CLr was calculated as Aetau/AUCtau.

Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted ConditionDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Data for AUClast and AUCinf are reported in the descriptive section. AUClast was calculated by the linear/log trapezoidal method. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. Ratio based on AUClast and AUCinf of tablet formulations under fed and fasted conditions were reported in statistical analysis.

Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted ConditionDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Data for Cmax are reported in the descriptive section. Ratio based on Cmax of tablet formulation under fed and fasted conditions were reported in statistical analysis.

Part 3: Time for Cmax (Tmax) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Tmax of PF-07817883 was reported in this outcome measure.

Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.

Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.

Part 3: Terminal Half-Life (t1/2) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

Part 3: Apparent Clearance (CL/F) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.

Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)

Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau\*kel).

Part 3: Number of Participants With TEAEsFrom start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

Part 3: Number of Participants With Laboratory Test AbnormalitiesFrom start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 days)

Laboratory parameters included: hematology (monocytes/leukocytes \>1.2\*ULN \[%\], partial thromboplastin time \>1.1\*ULN \[seconds\]) and urinalysis (urine hemoglobin \>=1, bacteria \>20 \[/lpf\]). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

Part 3: Number of Participants With Vital Signs Meeting Pre-Defined CriteriaUp to Day 3 of each period

Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm. 4. Number of participants with vital signs meeting any of the pre-defined criteria is reported in this outcome measure.

Part 3: Number of Participants With ECG AbnormalitiesUp to Day 3 of each period

Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.

Part 4: Time for Cmax (Tmax) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Tmax of PF-07817883 was reported in this outcome measure.

Part 4: Maximum Observed Concentration (Cmax) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Cmax of PF-07817883 was reported in this outcome measure.

Part 4: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.

Part 4: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.

Part 4: Terminal Half-Life (t1/2) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

Part 4: Apparent Clearance (CL/F) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.

Part 4: Apparent Volume of Distribution (Vz/F) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)

Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau\*kel).

Part 4: Number of Participants With TEAEsFrom start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

Part 4: Number of Participants With Laboratory Test AbnormalitiesFrom start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 days)

Laboratory parameters included: hematology (mean corpuscular volume \<0.9\*LLN \[cubic micrometer {um\^3}\], mean corpuscular hemoglobin \<0.9\*LLN \[picograms per cell {pg/cell}\], monocytes/leukocytes \>1.2\*ULN \[%\]). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

Part 4: Number of Participants With Vital Signs Meeting Pre-Defined CriteriaUp to Day 11

Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm.

Part 4: Number of Participants With ECG AbnormalitiesUp to Day 11

Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.

Part 5: Number of Participants With TEAEsFrom start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 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. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.

Part 5: Number of Participants With Laboratory Test AbnormalitiesFrom start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)

Laboratory parameters included: hematology (lymphocytes \<0.8\*LLN \[10\^3/mm3\], lymphocytes/leukocytes \<0.8\*LLN \[%\], neutrophils/leukocytes \<0.8\*LLN \[%\], monocytes/leukocytes \>1.2\*ULN \[%\]), chemistry (amylase \>1.5\*ULN \[units/liter\] {U/L}), and urinalysis (urine hemoglobin \>=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.

Part 5: Number of Participants With Vital Signs Meeting Pre-Defined CriteriaFrom start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)

Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm.

Part 5: Number of Participants With ECG AbnormalitiesFrom start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)

Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.

Part 5: Time for Cmax (Tmax) of MidazolamDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

Tmax of midazolam was reported in this outcome measure.

Part 5: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of MidazolamDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

AUClast of midazolam was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.

Part 5: Terminal Half-Life (t1/2) of MidazolamDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

t1/2 of midazolam was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

Part 5: Apparent Clearance (CL/F) of MidazolamDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

CL/F of midazolam was reported in this outcome measure. CL/F was calculated as dose/AUCinf.

Part 5: Apparent Volume of Distribution (Vz/F) of MidazolamDay 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm

Vz/F of midazolam was reported in this outcome measure. Vz/F was calculated as dose/(AUCinf\*kel).

Part 6: Maximum Observed Concentration (Cmax) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)

Cmax of PF-07817883 was reported in this outcome measure.

Part 6: Time for Cmax (Tmax) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)

Tmax of PF-07817883 was reported in this outcome measure.

Part 6: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)

AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.

Part 6: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)

AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.

Part 6: Terminal Half-Life (t1/2) of PF-07817883Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)

t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.

Trial Locations

Locations (2)

New Haven Clinical Research Unit

🇺🇸

New Haven, Connecticut, United States

Pfizer Clinical Research Unit - Brussels

🇧🇪

Brussels, Bruxelles-capitale, Région DE, Belgium

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