Healthy
Conditions
Keywords
Oral Antiviral, COVID-19, Protease Inhibitor, Mpro, PF-07817883
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.
Interventions
DRUGPF-07817883
Oral suspension or solid oral formulation(s)
DRUGPlacebo
Placebo suspension
DRUGMidazolam
midazolam oral solution
DRUGMoxifloxacin
Moxifloxacin 400 mg tablet
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
PART-1, 2 and 6 are double-blind, sponsor-open while PART-3, 4 and 5 are open label
Intervention model description
PART-1 and -2 are a randomized, double-blind, sponsor-open, placebo-controlled trial to evaluate safety, tolerability and PK of single and multiple escalating oral doses of PF 07817883 in healthy adult participants, respectively. PART-1 is crossover while PART-2 is parallel cohort study design. PART-2 of the study may also evaluate the safety, tolerability and PK in Japanese and Chinese participants. PART-3 is a randomized, open-label, cross-over, study to evaluate relative bioavailability and food effect of up to 2 new PF 07817883 oral formulations. PART-4 is an open label, non-randomized, single period cohort to evaluate the metabolism and excretion of PF 07817883. PART-5 is an open-label, randomized, cross-over cohort to evaluate the effect of steady state PF-07817883 on PK of midazolam in healthy participants. PART-6 is a sponsor-open, randomized, 3-treatment, 3-period, cross over study to evaluate safety, tolerability, and PK of PF 07817883 at supratherapeutic exposure.
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). 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 1: Number of Participants With Laboratory Test Abnormalities | From 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 4: Percentage of Total Dose Administered Recovered in Urine and Feces | Up to 144 hours post-dose | The percentage of total dose administered recovered in urine and feces was reported in this outcome measure. |
| Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Up 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) Abnormalities | Up 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 Abnormalities | From 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 Criteria | Up 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) Abnormalities | Up 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 Suspension | Day 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 Suspension | Day 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 Urine | Up 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 Feces | Up to 144 hours post-dose | The percentage of total dose administered recovered in feces was reported in this outcome measure. |
| Part 5: Maximum Observed Concentration (Cmax) of Midazolam | Day 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 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Midazolam | Day 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 6: Number of Participants With TEAEs | From 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 Abnormalities | From 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 Criteria | Up 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 Data | Up 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
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | 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) | 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 10 | 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) | 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 10 | Day 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 10 | Day 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 10 | Day 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 10 | Day 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 10 | Day 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 Condition | Day 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 Condition | Day 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-07817883 | Day 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: Maximum Observed Concentration (Cmax) of PF-07817883 | Day 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 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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 TEAEs | From 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 Abnormalities | From 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 Criteria | Up 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 Abnormalities | Up 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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 TEAEs | From 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 Abnormalities | From 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 Criteria | Up 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 Abnormalities | Up 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 TEAEs | From 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 1: Maximum Observed Concentration (Cmax) of PF-07817883 | Day 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 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | From 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 Abnormalities | From 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 Midazolam | Day 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 Midazolam | Day 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 Midazolam | Day 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 Midazolam | Day 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 Midazolam | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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. |
| Part 5: Number of Participants With Laboratory Test Abnormalities | From 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 1: Time for Cmax (Tmax) of PF-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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-07817883 | Day 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 10 | Day 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 10 | Day 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 10 | Day 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 10 | 12 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 10 | Day 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 10 | Day 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 10 | 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) | 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 10 | 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) | 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 10 | 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) | 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. |
Countries
Belgium, United States
Participant flow
Pre-assignment details
A total of 94 participants were enrolled across Belgium and United States.
Participants by arm
| Arm | Count |
|---|---|
| P1: C1: Placebo,Fast/PF-07817883 1500mg,Fast/PF-07817883 4000mg, Fast In this cohort (C), participants received a single dose of placebo as an oral suspension in the fasted (fast) state on Day 1 of Period 1 followed by a single dose of PF-07817883 1500 milligram (mg) as an oral suspension in the fasted state on Day 1 of Period 2. Participants were administered a single dose of PF-07817883 4000 mg as an oral suspension in the fasted state on Day 1 of Period 3. There was a washout of at least 5 days between two doses. | 2 |
| P1: C1: PF-07817883 150mg,Fast/Placebo,Fast/PF-07817883 4000mg,Fast Participants received a single dose of PF-07817883 150 mg as an oral suspension in the fasted state on Day 1 of Period 1 followed by a single dose of placebo as an oral suspension in the fasted state on Day 1 of Period 2. Participants were administered a single dose of PF-07817883 4000 mg as an oral suspension in the fasted state on Day 1 of Period 3. There was a washout of at least 5 days between two doses. | 2 |
| P1: C1: PF-07817883 150 mg,Fast/PF-07817883 1500mg,Fast/Placebo,Fast Participants received a single dose of PF-07817883 150 mg as an oral suspension in the fasted state on Day 1 of Period 1 followed by a single dose of PF-07817883 1500 mg as an oral suspension in the fasted state on Day 1 of Period 2. Participants were administered a single dose of placebo as an oral suspension in the fasted state on Day 1 of Period 3. There was a washout of at least 5 days between two doses. | 2 |
| P1: C1: PF-07817883 150 mg,Fast/PF-07817883 1500mg,Fast/PF-07817883 4000mg,Fast Participants received a single dose of PF-07817883 150 mg as an oral suspension in the fasted state on Day 1 of Period 1 followed by a single dose of PF-07817883 1500 mg as an oral suspension in the fasted state on Day 1 of Period 2. Participants were administered a single dose of PF-07817883 4000 mg as an oral suspension in the fasted state on Day 1 of Period 3. There was a washout of at least 5 days between two doses. | 2 |
| P1: C2: Placebo,Fast/PF-07817883 3000mg,Fast/Placebo,Fed Participants received a single dose of placebo as an oral suspension in the fasted state on Day 1 of Period 1 followed by a single dose of PF-07817883 3000 mg as an oral suspension in the fasted state on Day 1 of Period 2. Participants were administered a single dose of placebo as an oral suspension in the fed state on Day 1 of Period 3. There was a washout of at least 5 days between two doses. | 2 |
| P1: C2: PF-07817883 500mg,Fast/Placebo,Fast/PF-07817883 500mg,Fed Participants received a single dose of PF-07817883 500 mg as an oral suspension in the fasted state on Day 1 of Period 1 followed by a single dose of placebo as an oral suspension in the fasted state on Day 1 of Period 2. Participants were administered a single dose of PF-07817883 500 mg as an oral suspension in the fed state on Day 1 of Period 3. There was a washout of at least 5 days between two doses. | 2 |
| P1: C2: PF-07817883 500mg,Fast/PF-07817883 3000mg,Fast/PF-07817883 500mg,Fed Participants received a single dose of PF-07817883 500 mg as an oral suspension in the fasted state on Day 1 of Period 1 followed by a single dose of PF-07817883 3000 mg as an oral suspension in the fasted state on Day 1 of Period 2. Participants were administered a single dose of PF-07817883 500 mg as an oral suspension in the fed state on Day 1 of Period 3. There was a washout of at least 5 days between two doses. | 4 |
| Part 2: Placebo (Suspension) BID, Fasted Participants received placebo oral suspension twice a day (BID) administered every 12 hours on Days 1 to 9. On Day 10, participants received only one dose of placebo in the morning under fasted conditions. | 6 |
| Part 2: PF-07817883 200 mg (Suspension) BID, Fasted Participants received PF-07817883 200 mg oral suspension BID administered every 12 hours on Days 1 to 9. On Day 10, participants received only one dose of PF-07817883 200 mg in the morning under fasted conditions. | 4 |
| Part 2: PF-07817883 600 mg (Suspension) BID, Fasted Participants received PF-07817883 600 mg oral suspension BID administered every 12 hours on Days 1 to 9. On Day 10, participants received only one dose of PF-07817883 600 mg in the morning under fasted conditions. | 4 |
| Part 2: PF-07817883 1500 mg (Suspension) BID, Fasted Participants received PF-07817883 1500 mg oral suspension BID administered every 12 hours on Days 1 to 9. On Day 10, participants received only one dose of PF-07817883 1500 mg in the morning under fasted conditions. | 4 |
| Part 2: Placebo (Suspension) BID, Fasted, Chinese Chinese participants received placebo oral suspension BID administered every 12 hours on Days 1 to 9. On Day 10, participants received only one dose of placebo in the morning under fasted conditions. | 1 |
| Part 2: PF-07817883 600 mg (Suspension) BID, Fasted, Chinese Chinese participants received PF-07817883 600 mg oral suspension BID administered every 12 hours on Days 1 to 9. On Day 10, participants received only one dose of PF-07817883 600 mg in the morning under fasted conditions. | 3 |
| Part 3: Treatment Sequence ABCD Participants received treatments A, B, C and D in Period 1, 2, 3 and 4 respectively. Treatment A: Single dose of PF-07817883 spray dried dispersion (SDD) 600 mg tablets in fasted conditions. Treatment B: Single dose of PF-07817883 crystalline 600 mg tablet in fasted conditions. Treatment C: Single dose of PF-07817883 600 mg suspension in fasted conditions. Treatment D: Single dose of PF-07817883 SDD 600 mg tablet in fed conditions. There was a washout of at least 3 days between 2 doses. | 2 |
| Part 3: Treatment Sequence BCAD Participants received treatments B, C, A and D in Period 1, 2, 3 and 4 respectively. Treatment B: Single dose of PF-07817883 crystalline 600 mg tablet in fasted conditions. Treatment C: Single dose of PF-07817883 600 mg suspension in fasted conditions. Treatment A: Single dose of PF-07817883 SDD 600 mg tablets in fasted conditions. Treatment D: Single dose of PF-07817883 SDD 600 mg tablet in fed conditions. There was a washout of at least 3 days between 2 doses. | 2 |
| Part 3: Treatment Sequence CABD Participants received treatments C, A, B and D in Period 1, 2, 3 and 4 respectively. Treatment C: Single dose of PF-07817883 600 mg suspension in fasted conditions. Treatment A: Single dose of PF-07817883 SDD 600 mg tablets in fasted conditions. Treatment B: Single dose of PF-07817883 crystalline 600 mg tablet in fasted conditions. Treatment D: Single dose of PF-07817883 SDD 600 mg tablet in fed conditions. There was a washout of at least 3 days between 2 doses. | 2 |
| Part 3: Treatment Sequence BACE Participants received treatments B, A, C and E in Period 1, 2, 3 and 4 respectively. Treatment B: Single dose of PF-07817883 crystalline 600 mg tablet in fasted conditions. Treatment A: Single dose of PF-07817883 SDD 600 mg tablets in fasted conditions. Treatment C: Single dose of PF-07817883 600 mg suspension in fasted conditions. Treatment E: Single dose of PF-07817883 crystalline 600 mg tablet in fed conditions. There was a washout of at least 3 days between 2 doses. | 2 |
| Part 3: Treatment Sequence ACBE Participants received treatments A, C, B and E in Period 1, 2, 3 and 4 respectively. Treatment A: Single dose of PF-07817883 SDD 600 mg tablets in fasted conditions. Treatment C: Single dose of PF-07817883 600 mg suspension in fasted conditions. Treatment B: Single dose of PF-07817883 crystalline 600 mg tablet in fasted conditions. Treatment E: Single dose of PF-07817883 crystalline 600 mg tablet in fed conditions. There was a washout of at least 3 days between 2 doses. | 2 |
| Part 3: Treatment Sequence CBAE Participants received treatments C, B, A and E in Period 1, 2, 3 and 4 respectively. Treatment C: Single dose of PF-07817883 600 mg suspension in fasted conditions. Treatment B: Single dose of PF-07817883 crystalline 600 mg tablet in fasted conditions. Treatment A: Single dose of PF-07817883 SDD 600 mg tablets in fasted conditions. Treatment E: Single dose of PF-07817883 crystalline 600 mg tablet in fed conditions. There was a washout of at least 3 days between 2 doses. | 2 |
| Part 4: PF-07817883 600 mg (Suspension), Fasted Participants received a single dose of PF-07817883 600 mg oral suspension on Day 1 following an overnight fast of approximately 10 hours. | 6 |
| Part 5: Treatment Sequence AB Participants received a single dose of midazolam 5 mg orally on Day 1 of Period 1 followed by a 2-day washout period. In Period 2, participants received PF-07817883 BID orally for 10 days followed by single dose of midazolam 5 mg on Day 10 followed by a washout of at least 7 days. | 7 |
| Part 5: Treatment Sequence BA In Period 1, participants received PF-07817883 BID orally for 10 days and on Day 10, participants received a single oral dose of 5 mg midazolam administered with PF-07817883 followed by a washout of at least 7 days. In Period 2, participants received a single dose of midazolam 5 mg orally followed by a 2-day washout period. | 7 |
| Part 6: Treatment Sequence ABC Participants received treatment A, B and C in Period 1, 2 and 3 respectively. Treatment A: PF-07817883 6000 mg oral suspension administered as 2 split doses of 3000 mg at 0 and 1 hour under fasted conditions. Treatment B: Single dose of Placebo oral suspension following an overnight fast of at least 10 hours. Treatment C: Single dose of Moxifloxacin 400 mg oral tablet at 0 hour and placebo at 1 hour following an overnight fast of at least 10 hours. Each period was separated by a washout of at least 7 days. | 4 |
| Part 6: Treatment Sequence BCA Participants received treatment B, C and A in Period 1, 2 and 3 respectively. Treatment B: Single dose of Placebo oral suspension following an overnight fast of at least 10 hours. Treatment C: Single dose of Moxifloxacin 400 mg oral tablet at 0 hour and placebo at 1 hour following an overnight fast of at least 10 hours. Treatment A: PF-07817883 6000 mg oral suspension administered as 2 split doses of 3000 mg at 0 and 1 hour under fasted conditions. Each period was separated by a washout of at least 7 days. | 4 |
| Part 6: Treatment Sequence CAB Participants received treatment C, A and B in Period 1, 2 and 3 respectively. Treatment C: Single dose of Moxifloxacin 400 mg oral tablet at 0 hour and placebo at 1 hour following an overnight fast of at least 10 hours. Treatment A: PF-07817883 6000 mg oral suspension administered as 2 split doses of 3000 mg at 0 and 1 hour under fasted conditions. Treatment B: Single dose of Placebo oral suspension following an overnight fast of at least 10 hours. Each period was separated by a washout of at least 7 days. | 4 |
| Part 6: Treatment Sequence BAC Participants received treatment B, A and C in Period 1, 2 and 3 respectively. Treatment B: Single dose of Placebo oral suspension following an overnight fast of at least 10 hours. Treatment A: PF-07817883 6000 mg oral suspension administered as 2 split doses of 3000 mg at 0 and 1 hour under fasted conditions. Treatment C: Single dose of Moxifloxacin 400 mg oral tablet at 0 hour and placebo at 1 hour following an overnight fast of at least 10 hours. Each period was separated by a washout of at least 7 days. | 4 |
| Part 6: Treatment Sequence ACB Participants received treatment A, C and B in Period 1, 2 and 3 respectively. Treatment A: PF-07817883 6000 mg oral suspension administered as 2 split doses of 3000 mg at 0 and 1 hour under fasted conditions. Treatment C: Single dose of Moxifloxacin 400 mg oral tablet at 0 hour and placebo at 1 hour following an overnight fast of at least 10 hours. Treatment B: Single dose of Placebo oral suspension following an overnight fast of at least 10 hours. Each period was separated by a washout of at least 7 days. | 4 |
| Part 6: Treatment Sequence CBA Participants received treatment C, B and A in Period 1, 2 and 3 respectively. Treatment C: Single dose of Moxifloxacin 400 mg oral tablet at 0 hour and placebo at 1 hour following an overnight fast of at least 10 hours. Treatment B: Single dose of Placebo oral suspension following an overnight fast of at least 10 hours. Treatment A: PF-07817883 6000 mg oral suspension administered as 2 split doses of 3000 mg at 0 and 1 hour under fasted conditions. Each period was separated by a washout of at least 7 days. | 4 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 | FG026 | FG027 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 Treatment Period 2 (Day 1) | Other | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1 Treatment Period 2 (Day 1) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Treatment Period 3 (Day 1) | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 (up to 10 Days) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 4 (Day 1 to Day 11) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 5: Sequence AB: Period 1 (Day 1) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part5:Sequence BA:Period1(up to 10 Days) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 6 Period 2 (Day 1) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Part 6 Period 2 (Day 1) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part (P) 1 Treatment Period 1 (Day 1) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | P1: C1: Placebo,Fast/PF-07817883 1500mg,Fast/PF-07817883 4000mg, Fast | P1: C1: PF-07817883 150mg,Fast/Placebo,Fast/PF-07817883 4000mg,Fast | P1: C1: PF-07817883 150 mg,Fast/PF-07817883 1500mg,Fast/Placebo,Fast | P1: C1: PF-07817883 150 mg,Fast/PF-07817883 1500mg,Fast/PF-07817883 4000mg,Fast | P1: C2: Placebo,Fast/PF-07817883 3000mg,Fast/Placebo,Fed | P1: C2: PF-07817883 500mg,Fast/Placebo,Fast/PF-07817883 500mg,Fed | P1: C2: PF-07817883 500mg,Fast/PF-07817883 3000mg,Fast/PF-07817883 500mg,Fed | Part 2: Placebo (Suspension) BID, Fasted | Part 2: PF-07817883 200 mg (Suspension) BID, Fasted | Part 2: PF-07817883 600 mg (Suspension) BID, Fasted | Part 2: PF-07817883 1500 mg (Suspension) BID, Fasted | Part 2: Placebo (Suspension) BID, Fasted, Chinese | Part 2: PF-07817883 600 mg (Suspension) BID, Fasted, Chinese | Part 3: Treatment Sequence ABCD | Part 3: Treatment Sequence BCAD | Part 3: Treatment Sequence CABD | Part 3: Treatment Sequence BACE | Part 3: Treatment Sequence ACBE | Part 3: Treatment Sequence CBAE | Part 4: PF-07817883 600 mg (Suspension), Fasted | Part 5: Treatment Sequence AB | Part 5: Treatment Sequence BA | Part 6: Treatment Sequence ABC | Part 6: Treatment Sequence BCA | Part 6: Treatment Sequence CAB | Part 6: Treatment Sequence BAC | Part 6: Treatment Sequence ACB | Part 6: Treatment Sequence CBA | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 Years | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 64 Participants |
| Age, Customized 45-60 Years | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 29 Participants |
| Age, Customized Not Disclosed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 19 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 31 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 33 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Disclosed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 0 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 60 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 39 Participants |
| Sex/Gender, Customized Female | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 19 Participants |
| Sex/Gender, Customized Male | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 6 Participants | 4 Participants | 2 Participants | 4 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants | 5 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 4 Participants | 74 Participants |
| Sex/Gender, Customized Not Disclosed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 1 | 0 / 3 | 0 / 12 | 0 / 12 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 13 | 0 / 13 | 0 / 23 | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 4 / 10 | 1 / 2 | 2 / 6 | 1 / 6 | 0 / 4 | 3 / 6 | 0 / 5 | 1 / 5 | 2 / 6 | 1 / 4 | 0 / 4 | 2 / 4 | 0 / 1 | 2 / 3 | 4 / 12 | 1 / 12 | 1 / 6 | 4 / 12 | 2 / 6 | 4 / 6 | 11 / 13 | 10 / 13 | 0 / 23 | 0 / 23 | 0 / 24 |
| serious Total, serious adverse events | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 1 | 0 / 3 | 0 / 12 | 0 / 12 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 13 | 0 / 13 | 0 / 23 | 0 / 23 | 0 / 24 |
Outcome results
Primary
Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities
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.
Time frame: Up to Day 2 of each period
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
Primary
Part 1: Number of Participants With Laboratory Test Abnormalities
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.
Time frame: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Laboratory Test Abnormalities | 5 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
Primary
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
Primary
Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
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.
Time frame: Up to Day 2 of each period
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 0 Participants |
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| Placebo (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| Placebo (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 2 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 1 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 1 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 1 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 1 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 1 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| PF-07817883 3000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg decrease | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP Change >= 30 mmHg increase | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value < 40 bpm | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | PR Value > 120 bpm | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg decrease | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Value < 50 mmHg | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP Change >= 20 mmHg increase | 0 Participants |
| PF-07817883 4000 mg (Suspension), Fasted | Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 0 Participants |
Primary
Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities
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.
Time frame: Up to Day 12
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Placebo (Suspension), Fed | Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities | 0 Participants |
Primary
Part 2: Number of Participants With Laboratory Test Abnormalities
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.
Time frame: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| Placebo (Suspension), Fed | Part 2: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 2: Number of Participants With Laboratory Test Abnormalities | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 2: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
Primary
Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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.
Time frame: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| Placebo (Suspension), Fed | Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
Primary
Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
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.
Time frame: Up to Day 12
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| Placebo (Suspension), Fed | Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| PF-07817883 1500 mg (Suspension), Fasted | Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
Primary
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 Suspension
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | 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 Suspension | AUClast | 42540 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| Placebo (Suspension), Fasted | 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 Suspension | AUCinf | 42970 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| Placebo (Suspension), Fed | 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 Suspension | AUCinf | 44140 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| Placebo (Suspension), Fed | 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 Suspension | AUClast | 43570 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| PF-07817883 150 mg (Suspension), Fasted | 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 Suspension | AUCinf | 28430 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-07817883 150 mg (Suspension), Fasted | 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 Suspension | AUClast | 27750 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-07817883 500 mg (Suspension), Fasted | 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 Suspension | AUCinf | 42930 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| PF-07817883 500 mg (Suspension), Fasted | 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 Suspension | AUClast | 41620 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 41 |
| PF-07817883 500 mg (Suspension), Fed | 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 Suspension | AUClast | 35930 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
| PF-07817883 500 mg (Suspension), Fed | 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 Suspension | AUCinf | 46170 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
Comparison: AUCinf90% CI: [95.71, 107.18]
Comparison: AUCinf90% CI: [97.28, 108.5]
Comparison: AUClast90% CI: [91.32, 104.8]
Comparison: AUClast90% CI: [95.6, 109.7]
Primary
Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension
Data for Cmax are reported in the descriptive section. Ratio based on Cmax of oral formulation and suspension were reported in statistical analysis.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension | 9354 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| Placebo (Suspension), Fed | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension | 6934 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension | 4590 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension | 6284 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension | 5008 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
90% CI: [58.13, 77.65]
90% CI: [64.14, 85.67]
Primary
Part 4: Percentage of Total Dose Administered Recovered in Feces
The percentage of total dose administered recovered in feces was reported in this outcome measure.
Time frame: Up to 144 hours post-dose
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Percentage of Total Dose Administered Recovered in Feces | 88.9 Percentage dose excreted | Standard Deviation 10 |
Primary
Part 4: Percentage of Total Dose Administered Recovered in Urine
The percentage of total dose administered recovered in urine was reported in this outcome measure.
Time frame: Up to 144 hours post-dose
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Percentage of Total Dose Administered Recovered in Urine | 12.6 Percentage dose excreted | Standard Deviation 4.7 |
Primary
Part 4: Percentage of Total Dose Administered Recovered in Urine and Feces
The percentage of total dose administered recovered in urine and feces was reported in this outcome measure.
Time frame: Up to 144 hours post-dose
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Percentage of Total Dose Administered Recovered in Urine and Feces | 101.5 Percentage dose excreted | Standard Deviation 7.7 |
Primary
Part 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Midazolam
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.
Time frame: Day 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
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Midazolam | 94.30 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| Placebo (Suspension), Fed | Part 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Midazolam | 79.85 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
Primary
Part 5: Maximum Observed Concentration (Cmax) of Midazolam
Cmax of midazolam was reported in this outcome measure.
Time frame: Day 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
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Maximum Observed Concentration (Cmax) of Midazolam | 33.71 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| Placebo (Suspension), Fed | Part 5: Maximum Observed Concentration (Cmax) of Midazolam | 30.20 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Primary
Part 6: Number of Participants According to Categorization of ECG Data
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.
Time frame: Up to Day 6 of each period
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Number of Participants According to Categorization of ECG Data | QTCF interval, aggregate 450 msec < Value <= 480 msec | 0 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants According to Categorization of ECG Data | QTCF interval, aggregate 30 msec < Change <= 60 msec | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants According to Categorization of ECG Data | QTCF interval, aggregate 450 msec < Value <= 480 msec | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants According to Categorization of ECG Data | QTCF interval, aggregate 30 msec < Change <= 60 msec | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants According to Categorization of ECG Data | QTCF interval, aggregate 450 msec < Value <= 480 msec | 1 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants According to Categorization of ECG Data | QTCF interval, aggregate 30 msec < Change <= 60 msec | 1 Participants |
Primary
Part 6: Number of Participants With Laboratory Test Abnormalities
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.
Time frame: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Laboratory Test Abnormalities | 12 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Laboratory Test Abnormalities | 12 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Laboratory Test Abnormalities | 7 Participants |
Primary
Part 6: Number of Participants With TEAEs
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.
Time frame: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Number of Participants With TEAEs | 4 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With TEAEs | 6 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With TEAEs | 4 Participants |
Primary
Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
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.
Time frame: Up to Day 6 of each period
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value > 120 bpm | 0 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg increase | 0 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value < 40 bpm | 0 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 1 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP value < 50 mmHg | 0 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg increase | 0 Participants |
| Placebo (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP value < 50 mmHg | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 2 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value < 40 bpm | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg increase | 1 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value > 120 bpm | 0 Participants |
| Placebo (Suspension), Fed | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg increase | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value > 120 bpm | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 3 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg increase | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg decrease | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg increase | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg decrease | 1 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value < 40 bpm | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP value < 50 mmHg | 0 Participants |
Secondary
Part 1: Apparent Clearance (CL/F) of PF-07817883
CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Apparent Clearance (CL/F) of PF-07817883 | 13.33 Liter per hour (L/hr) | Geometric Coefficient of Variation 53 |
| Placebo (Suspension), Fed | Part 1: Apparent Clearance (CL/F) of PF-07817883 | 13.93 Liter per hour (L/hr) | Geometric Coefficient of Variation 25 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Apparent Clearance (CL/F) of PF-07817883 | 17.79 Liter per hour (L/hr) | Geometric Coefficient of Variation 28 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Apparent Clearance (CL/F) of PF-07817883 | 17.58 Liter per hour (L/hr) | Geometric Coefficient of Variation 35 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Apparent Clearance (CL/F) of PF-07817883 | 18.09 Liter per hour (L/hr) | Geometric Coefficient of Variation 35 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Apparent Clearance (CL/F) of PF-07817883 | 21.13 Liter per hour (L/hr) | Geometric Coefficient of Variation 19 |
Secondary
Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883
Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCinf\*kel).
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 86.87 Liter (L) | Geometric Coefficient of Variation 48 |
| Placebo (Suspension), Fed | Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 209.5 Liter (L) | Geometric Coefficient of Variation 101 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 366.1 Liter (L) | Geometric Coefficient of Variation 50 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 242.9 Liter (L) | Geometric Coefficient of Variation 80 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 367.4 Liter (L) | Geometric Coefficient of Variation 87 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 358.7 Liter (L) | Geometric Coefficient of Variation 44 |
Secondary
Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883
AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 10890 Nanogram*hour per milliliter | Geometric Coefficient of Variation 47 |
| Placebo (Suspension), Fed | Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 34580 Nanogram*hour per milliliter | Geometric Coefficient of Variation 25 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 27080 Nanogram*hour per milliliter | Geometric Coefficient of Variation 25 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 83490 Nanogram*hour per milliliter | Geometric Coefficient of Variation 36 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 160700 Nanogram*hour per milliliter | Geometric Coefficient of Variation 33 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 185700 Nanogram*hour per milliliter | Geometric Coefficient of Variation 17 |
Secondary
Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 11250 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 53 |
| Placebo (Suspension), Fed | Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 35950 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 28120 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 85320 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 166100 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 189400 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
Secondary
Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883
AUCinf(dn) of PF-07817883 was reported in this outcome measure. AUCinf(dn) was calculated as AUCinf/dose.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883 | 74.99 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 53 |
| Placebo (Suspension), Fed | Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883 | 71.81 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 25 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883 | 56.23 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 28 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883 | 56.86 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 34 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883 | 55.33 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 35 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883 | 47.34 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 19 |
Secondary
Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883
AUClast(dn) of PF-07817883 was reported in this outcome measure. AUClast(dn) was calculated by AUClast/dose.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883 | 72.61 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 47 |
| Placebo (Suspension), Fed | Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883 | 69.17 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 25 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883 | 54.16 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 25 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883 | 55.64 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 35 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883 | 53.53 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 33 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883 | 46.43 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 17 |
Secondary
Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883
Cmax(dn) of PF-07817883 was reported in this outcome measure. Cmax(dn) was calculated as Cmax/dose.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 | 15.14 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 51 |
| Placebo (Suspension), Fed | Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 | 12.48 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 19 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 | 6.445 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 13 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 | 11.61 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 36 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 | 11.49 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 12 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 | 8.672 Nanogram per milliliter per milligram | Geometric Coefficient of Variation 36 |
Secondary
Part 1: Maximum Observed Concentration (Cmax) of PF-07817883
Cmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Maximum Observed Concentration (Cmax) of PF-07817883 | 2269 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| Placebo (Suspension), Fed | Part 1: Maximum Observed Concentration (Cmax) of PF-07817883 | 6235 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Maximum Observed Concentration (Cmax) of PF-07817883 | 3223 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Maximum Observed Concentration (Cmax) of PF-07817883 | 17420 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Maximum Observed Concentration (Cmax) of PF-07817883 | 34420 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Maximum Observed Concentration (Cmax) of PF-07817883 | 34670 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
Secondary
Part 1: Terminal Half-Life (t1/2) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Terminal Half-Life (t1/2) of PF-07817883 | 4.534 Hours | Standard Deviation 0.50659 |
| Placebo (Suspension), Fed | Part 1: Terminal Half-Life (t1/2) of PF-07817883 | 13.88 Hours | Standard Deviation 10.838 |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Terminal Half-Life (t1/2) of PF-07817883 | 15.95 Hours | Standard Deviation 8.4657 |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Terminal Half-Life (t1/2) of PF-07817883 | 10.84 Hours | Standard Deviation 6.1747 |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Terminal Half-Life (t1/2) of PF-07817883 | 18.79 Hours | Standard Deviation 14.234 |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Terminal Half-Life (t1/2) of PF-07817883 | 13.05 Hours | Standard Deviation 7.3974 |
Secondary
Part 1: Time for Cmax (Tmax) of PF-07817883
Tmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 1: Time for Cmax (Tmax) of PF-07817883 | 1.00 Hours |
| Placebo (Suspension), Fed | Part 1: Time for Cmax (Tmax) of PF-07817883 | 0.792 Hours |
| PF-07817883 150 mg (Suspension), Fasted | Part 1: Time for Cmax (Tmax) of PF-07817883 | 1.25 Hours |
| PF-07817883 500 mg (Suspension), Fasted | Part 1: Time for Cmax (Tmax) of PF-07817883 | 0.500 Hours |
| PF-07817883 500 mg (Suspension), Fed | Part 1: Time for Cmax (Tmax) of PF-07817883 | 0.500 Hours |
| PF-07817883 1500 mg (Suspension), Fasted | Part 1: Time for Cmax (Tmax) of PF-07817883 | 1.00 Hours |
Secondary
Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10
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.
Time frame: Day 10 (0 to 12 hours)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10 | 18.47 Milligram (mg) | Geometric Coefficient of Variation 16 |
| Placebo (Suspension), Fed | Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10 | 96.86 Milligram (mg) | Geometric Coefficient of Variation 5 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10 | 373.2 Milligram (mg) | Geometric Coefficient of Variation 10 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10 | 85.85 Milligram (mg) | Geometric Coefficient of Variation 20 |
Secondary
Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10
CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.
Time frame: 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 5 | 10.83 Liter/hour (L/hr) | Geometric Coefficient of Variation 15 |
| Placebo (Suspension), Fasted | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 10 | 11.60 Liter/hour (L/hr) | Geometric Coefficient of Variation 10 |
| Placebo (Suspension), Fed | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 10 | 17.13 Liter/hour (L/hr) | Geometric Coefficient of Variation 8 |
| Placebo (Suspension), Fed | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 5 | 16.57 Liter/hour (L/hr) | Geometric Coefficient of Variation 10 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 10 | 14.37 Liter/hour (L/hr) | Geometric Coefficient of Variation 18 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 5 | 13.12 Liter/hour (L/hr) | Geometric Coefficient of Variation 22 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 5 | 15.88 Liter/hour (L/hr) | Geometric Coefficient of Variation 29 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10 | Day 10 | 17.32 Liter/hour (L/hr) | Geometric Coefficient of Variation 29 |
Secondary
Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10
Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau\*kel).
Time frame: Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10 | 200.1 Liter | Geometric Coefficient of Variation 84 |
| Placebo (Suspension), Fed | Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10 | 279.6 Liter | Geometric Coefficient of Variation 62 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10 | 198.1 Liter | Geometric Coefficient of Variation 98 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10 | 186.0 Liter | Geometric Coefficient of Variation 115 |
Secondary
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 10
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.
Time frame: Day 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | 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 10 | Day 10 | 17180 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 10 |
| Placebo (Suspension), Fasted | 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 10 | Day 1 | 14760 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| Placebo (Suspension), Fasted | 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 10 | Day 5 | 18460 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 15 |
| Placebo (Suspension), Fed | 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 10 | Day 5 | 36300 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 10 |
| Placebo (Suspension), Fed | 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 10 | Day 1 | 36440 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| Placebo (Suspension), Fed | 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 10 | Day 10 | 34960 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 8 |
| PF-07817883 150 mg (Suspension), Fasted | 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 10 | Day 10 | 103900 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 18 |
| PF-07817883 150 mg (Suspension), Fasted | 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 10 | Day 1 | 108400 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 15 |
| PF-07817883 150 mg (Suspension), Fasted | 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 10 | Day 5 | 114000 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 22 |
| PF-07817883 500 mg (Suspension), Fasted | 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 10 | Day 5 | 37680 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-07817883 500 mg (Suspension), Fasted | 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 10 | Day 1 | 36880 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 22 |
| PF-07817883 500 mg (Suspension), Fasted | 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 10 | Day 10 | 34650 Nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
Secondary
Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10
Cav of PF-07817883 was reported in this outcome measure. Cav was calculated as AUCtau/12.
Time frame: 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 5 | 1542 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| Placebo (Suspension), Fasted | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 10 | 1434 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| Placebo (Suspension), Fed | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 10 | 2914 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 8 |
| Placebo (Suspension), Fed | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 5 | 3022 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 5 | 9515 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 10 | 8672 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 5 | 3140 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10 | Day 10 | 2890 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
Secondary
Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10
C12 of PF-07817883 was reported in this outcome measure.
Time frame: 12 hours on Day 5 and Day 10
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 5 | 389.3 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| Placebo (Suspension), Fasted | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 10 | 425.7 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 12 |
| Placebo (Suspension), Fed | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 10 | 865.9 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| Placebo (Suspension), Fed | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 5 | 734.5 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 5 | 2598 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 10 | 2315 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 5 | 716.0 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10 | Day 10 | 585.5 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Secondary
Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10
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.
Time frame: Day 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 73.94 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 26 |
| Placebo (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 86.04 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 10 |
| Placebo (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 92.46 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 15 |
| Placebo (Suspension), Fed | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 60.70 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 27 |
| Placebo (Suspension), Fed | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 60.49 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 10 |
| Placebo (Suspension), Fed | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 58.28 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 8 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 76.20 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 23 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 72.25 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 15 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 69.43 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 18 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 57.78 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 29 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 62.82 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 29 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 61.44 Nanogram*hour/milliliter/milligram | Geometric Coefficient of Variation 22 |
Secondary
Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10
Cmax(dn) of PF-07817883 was reported in this outcome measure. Cmax(dn) was calculated as Cmax/dose.
Time frame: Day 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 17.93 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 20 |
| Placebo (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 17.47 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 15 |
| Placebo (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 21.18 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 7 |
| Placebo (Suspension), Fed | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 14.15 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 39 |
| Placebo (Suspension), Fed | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 13.07 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 21 |
| Placebo (Suspension), Fed | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 15.20 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 13 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 18.35 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 22 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 16.07 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 22 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 15.61 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 14 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 14.00 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 12 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 12.20 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 25 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 13.76 Nanogram/milliliter/milligram (ng/mL/mg) | Geometric Coefficient of Variation 18 |
Secondary
Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10
Cmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 3582 Nanogram/milliliter | Geometric Coefficient of Variation 20 |
| Placebo (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 3492 Nanogram/milliliter | Geometric Coefficient of Variation 15 |
| Placebo (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 4234 Nanogram/milliliter | Geometric Coefficient of Variation 7 |
| Placebo (Suspension), Fed | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 8470 Nanogram/milliliter | Geometric Coefficient of Variation 39 |
| Placebo (Suspension), Fed | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 7852 Nanogram/milliliter | Geometric Coefficient of Variation 21 |
| Placebo (Suspension), Fed | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 9112 Nanogram/milliliter | Geometric Coefficient of Variation 14 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 27530 Nanogram/milliliter | Geometric Coefficient of Variation 22 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 24100 Nanogram/milliliter | Geometric Coefficient of Variation 22 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 23420 Nanogram/milliliter | Geometric Coefficient of Variation 14 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 8381 Nanogram/milliliter | Geometric Coefficient of Variation 12 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 7306 Nanogram/milliliter | Geometric Coefficient of Variation 25 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 8260 Nanogram/milliliter | Geometric Coefficient of Variation 18 |
Secondary
Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10
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.
Time frame: 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 5 | 1.250 Ratio | Geometric Coefficient of Variation 28 |
| Placebo (Suspension), Fasted | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 10 | 1.163 Ratio | Geometric Coefficient of Variation 18 |
| Placebo (Suspension), Fed | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 5 | 0.9972 Ratio | Geometric Coefficient of Variation 18 |
| Placebo (Suspension), Fed | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 10 | 0.8962 Ratio | Geometric Coefficient of Variation 20 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 5 | 1.054 Ratio | Geometric Coefficient of Variation 9 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 10 | 0.9605 Ratio | Geometric Coefficient of Variation 4 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 10 | 0.9412 Ratio | Geometric Coefficient of Variation 8 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10 | Day 5 | 1.022 Ratio | Geometric Coefficient of Variation 7 |
Secondary
Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10
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.
Time frame: 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 10 | 0.9744 Ratio | Geometric Coefficient of Variation 20 |
| Placebo (Suspension), Fasted | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 5 | 1.183 Ratio | Geometric Coefficient of Variation 22 |
| Placebo (Suspension), Fed | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 10 | 0.8471 Ratio | Geometric Coefficient of Variation 36 |
| Placebo (Suspension), Fed | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 5 | 1.075 Ratio | Geometric Coefficient of Variation 30 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 5 | 1.142 Ratio | Geometric Coefficient of Variation 33 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 10 | 0.9717 Ratio | Geometric Coefficient of Variation 18 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 10 | 0.8712 Ratio | Geometric Coefficient of Variation 21 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10 | Day 5 | 0.9844 Ratio | Geometric Coefficient of Variation 18 |
Secondary
Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10
PTR of PF-07817883 was reported in this outcome measure. PTR was calculated as Cmax/Cmin.
Time frame: 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 5 | 10.88 Ratio | Geometric Coefficient of Variation 10 |
| Placebo (Suspension), Fasted | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 10 | 8.566 Ratio | Geometric Coefficient of Variation 14 |
| Placebo (Suspension), Fed | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 5 | 13.47 Ratio | Geometric Coefficient of Variation 21 |
| Placebo (Suspension), Fed | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 10 | 11.05 Ratio | Geometric Coefficient of Variation 30 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 10 | 10.13 Ratio | Geometric Coefficient of Variation 23 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 5 | 10.60 Ratio | Geometric Coefficient of Variation 49 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 10 | 12.46 Ratio | Geometric Coefficient of Variation 9 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10 | Day 5 | 13.22 Ratio | Geometric Coefficient of Variation 10 |
Secondary
Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10
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.
Time frame: Day 10 (0 to 12 hours)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10 | 9.261 Percentage of Dose Excreted | Geometric Coefficient of Variation 16 |
| Placebo (Suspension), Fed | Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10 | 16.15 Percentage of Dose Excreted | Geometric Coefficient of Variation 5 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10 | 24.90 Percentage of Dose Excreted | Geometric Coefficient of Variation 10 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10 | 14.34 Percentage of Dose Excreted | Geometric Coefficient of Variation 20 |
Secondary
Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10
CLr of PF-07817883 was reported in this outcome measure. CLr was calculated as Aetau/AUCtau.
Time frame: Day 10 (0 to 12 hours)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10 | 1.074 Liter/hour (L/hr) | Geometric Coefficient of Variation 20 |
| Placebo (Suspension), Fed | Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10 | 2.771 Liter/hour (L/hr) | Geometric Coefficient of Variation 5 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10 | 3.586 Liter/hour (L/hr) | Geometric Coefficient of Variation 26 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10 | 2.477 Liter/hour (L/hr) | Geometric Coefficient of Variation 51 |
Secondary
Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10
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.
Time frame: Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10 | 13.95 Hours | Standard Deviation 9.3938 |
| Placebo (Suspension), Fed | Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10 | 13.01 Hours | Standard Deviation 8.8563 |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10 | 11.44 Hours | Standard Deviation 6.8367 |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10 | 8.587 Hours | Standard Deviation 5.8524 |
Secondary
Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10
Tmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 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)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 0.759 Hours |
| Placebo (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 0.500 Hours |
| Placebo (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 0.859 Hours |
| Placebo (Suspension), Fed | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 0.775 Hours |
| Placebo (Suspension), Fed | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 0.500 Hours |
| Placebo (Suspension), Fed | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 0.500 Hours |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 0.500 Hours |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 0.500 Hours |
| PF-07817883 150 mg (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 0.500 Hours |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 1 | 1.00 Hours |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 10 | 0.533 Hours |
| PF-07817883 500 mg (Suspension), Fasted | Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10 | Day 5 | 0.500 Hours |
Secondary
Part 3: Apparent Clearance (CL/F) of PF-07817883
CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Apparent Clearance (CL/F) of PF-07817883 | 13.97 Liter/hour | Geometric Coefficient of Variation 35 |
| Placebo (Suspension), Fed | Part 3: Apparent Clearance (CL/F) of PF-07817883 | 13.58 Liter/hour | Geometric Coefficient of Variation 38 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Apparent Clearance (CL/F) of PF-07817883 | 21.09 Liter/hour | Geometric Coefficient of Variation 28 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Apparent Clearance (CL/F) of PF-07817883 | 13.98 Liter/hour | Geometric Coefficient of Variation 43 |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Apparent Clearance (CL/F) of PF-07817883 | 12.98 Liter/hour | Geometric Coefficient of Variation 27 |
Secondary
Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883
Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau\*kel).
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 136.2 Liter | Geometric Coefficient of Variation 55 |
| Placebo (Suspension), Fed | Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 136.7 Liter | Geometric Coefficient of Variation 50 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 302.2 Liter | Geometric Coefficient of Variation 31 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 120.7 Liter | Geometric Coefficient of Variation 55 |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 192.8 Liter | Geometric Coefficient of Variation 64 |
Secondary
Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883
AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 42540 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| Placebo (Suspension), Fed | Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 43570 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 27750 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 41620 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 41 |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 35930 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
Secondary
Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 42970 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| Placebo (Suspension), Fed | Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 44140 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 28430 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 42930 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 46170 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
Secondary
Part 3: Maximum Observed Concentration (Cmax) of PF-07817883
Cmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Maximum Observed Concentration (Cmax) of PF-07817883 | 9354 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| Placebo (Suspension), Fed | Part 3: Maximum Observed Concentration (Cmax) of PF-07817883 | 6934 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Maximum Observed Concentration (Cmax) of PF-07817883 | 4590 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Maximum Observed Concentration (Cmax) of PF-07817883 | 6284 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Maximum Observed Concentration (Cmax) of PF-07817883 | 5008 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
Secondary
Part 3: Number of Participants With ECG Abnormalities
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.
Time frame: Up to Day 3 of each period
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Number of Participants With ECG Abnormalities | 0 Participants |
| Placebo (Suspension), Fed | Part 3: Number of Participants With ECG Abnormalities | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Number of Participants With ECG Abnormalities | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Number of Participants With ECG Abnormalities | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Number of Participants With ECG Abnormalities | 0 Participants |
Secondary
Part 3: Number of Participants With Laboratory Test Abnormalities
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.
Time frame: From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Number of Participants With Laboratory Test Abnormalities | 0 Participants |
| Placebo (Suspension), Fed | Part 3: Number of Participants With Laboratory Test Abnormalities | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Number of Participants With Laboratory Test Abnormalities | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
Secondary
Part 3: Number of Participants With TEAEs
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.
Time frame: From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Number of Participants With TEAEs | 4 Participants |
| Placebo (Suspension), Fed | Part 3: Number of Participants With TEAEs | 1 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Number of Participants With TEAEs | 1 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Number of Participants With TEAEs | 4 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Number of Participants With TEAEs | 2 Participants |
Secondary
Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
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.
Time frame: Up to Day 3 of each period
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| Placebo (Suspension), Fed | Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | 0 Participants |
Secondary
Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number Analyzed'' signifies participants evaluable for the specified rows. This outcome measure was planned to be analyzed only in the tablet formulation as pre-specified in the protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUCinf | 44140 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| Placebo (Suspension), Fasted | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUClast | 43570 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 37 |
| Placebo (Suspension), Fed | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUCinf | 28430 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Placebo (Suspension), Fed | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUClast | 27750 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUClast | 41620 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 41 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUCinf | 42930 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUClast | 35930 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition | AUCinf | 46170 Nanogram*Hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
Comparison: AUCinf90% CI: [60.98, 87.09]
Comparison: AUCinf90% CI: [68.35, 85.52]
Comparison: AUClast90% CI: [65.7, 82.27]
Comparison: AUClast90% CI: [66.36, 85.13]
Secondary
Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted Condition
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. This outcome measure was planned to be analyzed only in the tablet formulation as pre-specified in the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted Condition | 6934 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Placebo (Suspension), Fed | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted Condition | 4590 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted Condition | 6284 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted Condition | 5008 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
90% CI: [60.21, 97.75]
90% CI: [53.7, 93.67]
Secondary
Part 3: Terminal Half-Life (t1/2) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, ''Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Terminal Half-Life (t1/2) of PF-07817883 | 7.578 Hours | Standard Deviation 3.2536 |
| Placebo (Suspension), Fed | Part 3: Terminal Half-Life (t1/2) of PF-07817883 | 7.957 Hours | Standard Deviation 3.874 |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Terminal Half-Life (t1/2) of PF-07817883 | 10.15 Hours | Standard Deviation 2.289 |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Terminal Half-Life (t1/2) of PF-07817883 | 6.822 Hours | Standard Deviation 3.5964 |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Terminal Half-Life (t1/2) of PF-07817883 | 11.07 Hours | Standard Deviation 4.4518 |
Secondary
Part 3: Time for Cmax (Tmax) of PF-07817883
Tmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 3: Time for Cmax (Tmax) of PF-07817883 | 0.750 Hours |
| Placebo (Suspension), Fed | Part 3: Time for Cmax (Tmax) of PF-07817883 | 1.01 Hours |
| PF-07817883 150 mg (Suspension), Fasted | Part 3: Time for Cmax (Tmax) of PF-07817883 | 4.00 Hours |
| PF-07817883 500 mg (Suspension), Fasted | Part 3: Time for Cmax (Tmax) of PF-07817883 | 1.34 Hours |
| PF-07817883 500 mg (Suspension), Fed | Part 3: Time for Cmax (Tmax) of PF-07817883 | 4.00 Hours |
Secondary
Part 4: Apparent Clearance (CL/F) of PF-07817883
CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Apparent Clearance (CL/F) of PF-07817883 | 16.26 Liter/hour | Geometric Coefficient of Variation 26 |
Secondary
Part 4: Apparent Volume of Distribution (Vz/F) of PF-07817883
Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau\*kel).
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Apparent Volume of Distribution (Vz/F) of PF-07817883 | 146.7 Liter | Geometric Coefficient of Variation 36 |
Secondary
Part 4: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883
AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 35520 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
Secondary
Part 4: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 36910 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
Secondary
Part 4: Maximum Observed Concentration (Cmax) of PF-07817883
Cmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Maximum Observed Concentration (Cmax) of PF-07817883 | 6791 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
Secondary
Part 4: Number of Participants With ECG Abnormalities
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.
Time frame: Up to Day 11
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Number of Participants With ECG Abnormalities | 0 Participants |
Secondary
Part 4: Number of Participants With Laboratory Test Abnormalities
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.
Time frame: From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Laboratory Test Abnormalities | 1 Participants |
Secondary
Part 4: Number of Participants With TEAEs
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.
Time frame: From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Number of Participants With TEAEs | 4 Participants |
Secondary
Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
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.
Time frame: Up to Day 11
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value < 40 bpm | 0 Participants |
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value > 120 bpm | 0 Participants |
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 1 Participants |
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg increase | 0 Participants |
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP value < 50 mmHg | 1 Participants |
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg increase | 0 Participants |
| Placebo (Suspension), Fasted | Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg decrease | 0 Participants |
Secondary
Part 4: Terminal Half-Life (t1/2) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Terminal Half-Life (t1/2) of PF-07817883 | 6.882 Hours | Standard Deviation 3.0621 |
Secondary
Part 4: Time for Cmax (Tmax) of PF-07817883
Tmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 4: Time for Cmax (Tmax) of PF-07817883 | 0.500 Hours |
Secondary
Part 5: Apparent Clearance (CL/F) of Midazolam
CL/F of midazolam was reported in this outcome measure. CL/F was calculated as dose/AUCinf.
Time frame: Day 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
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Apparent Clearance (CL/F) of Midazolam | 53.02 Liter/hour | Geometric Coefficient of Variation 26 |
| Placebo (Suspension), Fed | Part 5: Apparent Clearance (CL/F) of Midazolam | 62.60 Liter/hour | Geometric Coefficient of Variation 31 |
Secondary
Part 5: Apparent Volume of Distribution (Vz/F) of Midazolam
Vz/F of midazolam was reported in this outcome measure. Vz/F was calculated as dose/(AUCinf\*kel).
Time frame: Day 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
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Apparent Volume of Distribution (Vz/F) of Midazolam | 488.5 Liter | Geometric Coefficient of Variation 44 |
| Placebo (Suspension), Fed | Part 5: Apparent Volume of Distribution (Vz/F) of Midazolam | 598.9 Liter | Geometric Coefficient of Variation 45 |
Secondary
Part 5: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam
AUClast of midazolam was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.
Time frame: Day 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
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam | 92.37 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| Placebo (Suspension), Fed | Part 5: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam | 77.46 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
Secondary
Part 5: Number of Participants With ECG Abnormalities
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.
Time frame: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Number of Participants With ECG Abnormalities | 0 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With ECG Abnormalities | 0 Participants |
Secondary
Part 5: Number of Participants With Laboratory Test Abnormalities
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.
Time frame: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Laboratory Test Abnormalities | 5 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Laboratory Test Abnormalities | 2 Participants |
Secondary
Part 5: Number of Participants With TEAEs
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.
Time frame: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Number of Participants With TEAEs | 11 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With TEAEs | 10 Participants |
Secondary
Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
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.
Time frame: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 3 Participants |
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg increase | 0 Participants |
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP value < 50 mmHg | 2 Participants |
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg increase | 0 Participants |
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value < 40 bpm | 0 Participants |
| Placebo (Suspension), Fasted | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value > 120 bpm | 0 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value > 120 bpm | 0 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP value < 90 mmHg | 3 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg increase | 0 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg increase | 0 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | Pulse rate value < 40 bpm | 0 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | SBP change >= 30 mmHg decrease | 1 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo (Suspension), Fed | Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria | DBP value < 50 mmHg | 2 Participants |
Secondary
Part 5: Terminal Half-Life (t1/2) of Midazolam
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.
Time frame: Day 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
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Terminal Half-Life (t1/2) of Midazolam | 6.589 Hours | Standard Deviation 1.6566 |
| Placebo (Suspension), Fed | Part 5: Terminal Half-Life (t1/2) of Midazolam | 6.923 Hours | Standard Deviation 1.9185 |
Secondary
Part 5: Time for Cmax (Tmax) of Midazolam
Tmax of midazolam was reported in this outcome measure.
Time frame: Day 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
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 5: Time for Cmax (Tmax) of Midazolam | 0.500 Hours |
| Placebo (Suspension), Fed | Part 5: Time for Cmax (Tmax) of Midazolam | 0.500 Hours |
Secondary
Part 6: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883
AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. This outcome measure was planned to be analyzed only in the PF-07817883 6000 mg (suspension), fasted arm, as pre-specified in the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883 | 248300 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 17 |
Secondary
Part 6: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure. This outcome measure was planned to be analyzed only in the PF-07817883 6000 mg (suspension), fasted arm, as pre-specified in the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883 | 253000 Nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 17 |
Secondary
Part 6: Maximum Observed Concentration (Cmax) of PF-07817883
Cmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. This outcome measure was planned to be analyzed only in the PF-07817883 6000 mg (suspension), fasted arm, as pre-specified in the protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Maximum Observed Concentration (Cmax) of PF-07817883 | 53160 Nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
Secondary
Part 6: Terminal Half-Life (t1/2) of PF-07817883
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.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure. This outcome measure was planned to be analyzed only in the PF-07817883 6000 mg (suspension), fasted arm, as pre-specified in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Terminal Half-Life (t1/2) of PF-07817883 | 12.64 Hours | Standard Deviation 7.1787 |
Secondary
Part 6: Time for Cmax (Tmax) of PF-07817883
Tmax of PF-07817883 was reported in this outcome measure.
Time frame: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest were reported. This outcome measure was planned to be analyzed only in the PF-07817883 6000 mg (suspension), fasted arm, as pre-specified in the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Suspension), Fasted | Part 6: Time for Cmax (Tmax) of PF-07817883 | 1.00 Hours |