Healthy Participants
Conditions
Keywords
PF-07258669, multiple dose, melanocortin-4 receptor, MC4R, healthy participants, safety, tolerability, pharmacokinetics
Brief summary
Part A of this study is to evaluate safety, tolerability, and pharmacokinetics (PK) of PF-07258669 after administration of multiple ascending oral doses to healthy adult participants. Optional cohorts of healthy adult Japanese participants and/or older adult participants may also be evaluated if results in other cohorts support further evaluation. Part B of this study is a 2-period, fixed-sequence, multiple-dose, open-label design to evaluate the effect of PF-07258669 on midazolam PK in healthy adult participants. Part B will be conducted if the results of Part A support further evaluation of PF-07258669.
Interventions
DRUGPF-07258669
PF-07258669 will be administered as tablets; every 8 hour (Q8H) or every 12 hour (Q12H) over 14 days
DRUGPlacebo
Placebo will be administered as tablets; Q8H or Q12H over 14 days
DRUGMidazolam
Single doses of Midazolam will be administered as oral solution alone and in combination with PF-07258669
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. For optional cohort of older adult participants only: Male participants and female participants of non childbearing potential must be 65 to 90 years of age, inclusive, at the time of signing the ICD (informed consent document). Attempts will be made to ensure that the age composition of this cohort (eg, approximately 70% of participants ≥70 years of age) is comparable to that of the anticipated patient population in later clinical studies. 2. Female participants of nonchildbearing potential and male participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. For optional cohort of older adult participants only: Participants must be in a stable condition at admission. These participants must be in reasonably good health as determined by the investigator based on a detailed medical history, full physical examination, vital signs assessments, 12-lead ECG (electrocardiogram), and clinical laboratory tests. Participants with mild, chronic, stable disease (eg, controlled hypertension, noninsulin dependent diabetes, osteoarthritis) may be enrolled if deemed medically prudent by the investigator. 3. Participants who are willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure from admission to the follow-up contact and to apply sunscreen/lotion with a high sun protection factor and to wear eye protection, as appropriate. 4. Body mass index (BMI) of 17.5 to 28.5 kg/m2; and a total body weight \>50 kg (110 lb). For optional cohort of older adult participants only: BMI of 17.5 to 32.4 kg/m2; and a total body weight \>50 kg (110 lbs). Efforts will be made to enroll at least 3 older adult participants with BMI \<25 kg/m2, if feasible. 5. Japanese participants only: Participants enrolling as Japanese must have 4 biological Japanese grandparents who were born in Japan.
Exclusion criteria
1. Evidence or history of clinically significant hematological, renal, endocrine (including, but not limited to, thyroid disease, diabetes insipidus), pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including, but not limited to, primary polydipsia, obsessive compulsive disorder, anxiety disorder, schizophrenia), neurological (including, but not limited to, seizure disorder, traumatic brain injury), immunodeficiency (including, but not limited to, severe infection that required ICU admission, prolonged hospitalization, or prolonged treatment) or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing), as well as presence of clinical laboratory abnormalities. For optional cohort of older adult participants only: Participants with chronic conditions (eg, hypertension) that are controlled by either diet or stable doses of medications may be included. Recent evidence (ie, within previous 6 months) or history of unstable disease or moderate to severe conditions which would, in the investigator's opinion, interfere with the study evaluations or have an impact on the safety of participants. 2. History of symptomatic orthostatic hypotension or symptomatic bradycardia. 3. History of eating disorders (eg, anorexia or bulimia nervosa, binge-eating disorder, avoidant/restrictive food intake disorder). 4. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention. For optional cohort of older adult participants only: Participants taking daily prescription or non-prescription medications (that are not moderate or strong cytochrome P450 (CYP3A) inducers or inhibitors) for management of acceptable chronic medical conditions are to be on a stable dose, as defined by no change in dose for the 28 days or 5 half-lives (whichever is longer) before the screening visit. 1. Use of stable concomitant mediations noted above that are CYP3A substrates may be restricted. 2. All medications must be reviewed on a case-by-case basis by the investigator and approved by the sponsor during the screening period for eligibility purposes. 5. Use of moderate or strong cytochrome P450 3A (CYP3A) inhibitors or inducers within 28 days or 5 half-lives (whichever is longer) prior to first dose of study intervention. 6. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). 7. Fasting serum triglycerides \>2× ULN (upper limit of normal).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 | Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10 | AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time. |
| Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing]) | All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by clinical research unit (CRU) staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours. |
| Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | Part A: Day -1 (1 day prior to dosing) | All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours. |
| Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | Part A: Day 7 | All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours. |
| Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | Part A: Day 14 | All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours. |
| Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone on Day 1 of Period 1 | Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1 | Cmax was defined as the maximum observed plasma concentration. |
| Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 | Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2 | Cmax is the maximum observed plasma concentration. |
| Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 | Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10 | Cmax was defined as the maximum observed plasma concentration. |
| Part B: Area Under the Plasma Concentration-Time Curve From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam Alone on Day 1 of Period 1 | Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1 | AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. |
| Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 | Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2 | AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. |
| Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 | Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10 | AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. |
| Part B: Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam Alone on Day 1 of Period 1 | Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1 | AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time. |
| Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 | Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2 | AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time. |
| Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study intervention and up to 35 days after last dose of study intervention that were absent before treatment or that worsened after treatment. |
| Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days) | Laboratory assessments included clinical chemistry, hematology, and urinalysis. Abnormality was determined based on the criteria specified in the sponsor reporting standards. The primary criteria was less than (\<) 0.8\* lower limit of normal (LLN) for lymphocytes and lymphocytes/leukocytes, greater than (\>) 1.2\* upper limit of normal (ULN) for lymphocytes, eosinophils/leukocytes, monocytes, and monocytes/leukocytes; greater than (\>) 3.0\* ULN for alanine aminotransferase, \>1.3\* ULN for urea nitrogen, cholesterol, and triglycerides; \>1.030 for specific gravity (scalar), greater than or equal to (\>=) 1 for ketones, urine protein, urine hemoglobin, urine bilirubin, leukocyte esterase. |
| Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days) | Vital signs included: a) supine systolic blood pressure (SBP): change greater than or equal to (\>=) 30 millimeters of mercury (mmHg) increase, postural difference (supine standing) \>= 20 mmHg, standing systolic SBP (mmHg) less than (\<) 90 mmHg, \>= 160 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; b) supine diastolic blood pressure (DBP) \< 50 mmHg, \>= 90 mmHg, change \>= 20 mmHg increase, change \>= 20mmHg decrease; postural difference (supine standing) \>= 10 mmHg; standing \<50 mmHg, value \>=90 mmHg, change \>=20 mmHg increase, change \>=20 mmHg decrease, C) standing pulse rate (PR) greater than (\>) 140 bpm. Baseline for supine BP and pulse rate was defined as the average of the triplicate measurements collected at the pre-dose (0 hour) assessment on Day 1. Baseline for standing BP, standing pulse rate, respiratory rate and oral body temperature were defined as the pre-dose (0 hour) assessment on Day 1. |
| Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days) | ECG criteria: QTc corrected using Fridericia's formula (QTCF) interval aggregate in milliseconds (msec): less than or equal to (\<=) change \<= 60 msec. Baseline was defined as the average of the triplicate ECG measurements over the 3 pre-dose measurement times (-1 hour, -0.5 hour, and pre-dose 0 hour; total of 9 ECG measurements) on Day 1. |
| Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing]) | C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported. |
| Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | Part A: On Day -2 (2 days prior to dosing) | C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported. |
| Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | Part A: On Day 7 | C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported. |
| Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | Part A: Day 14 | C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported. |
| Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | Part A: Day 21 | C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14 | Cmax was defined as the maximum plasma concentration. |
| Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14 | Cmax was defined maximum observed serum concentration. Cmax (dn) was calculated as Cmax/dose. |
| Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14 | Area under the plasma concentration-time profile from time zero to time tau, the dosing interval, where tau = 8 hours. |
| Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14 | — |
| Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14 | Tmax was defined as the time taken (in hours) to reach the maximum plasma drug concentration. |
| Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14 | Aetau was defined as the amount of unchanged drug recovered in urine during the dosing interval. |
| Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14 | Aetau% was defined as the percentage of dose recovered in urine as unchanged drug. |
| Part B: Number of Participants With TEAEs | Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days) | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. |
| Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days) | Vital signs examination included: supine systolic blood pressure with criteria change \>= 30 mmHg decrease, supine diastolic blood pressure with criteria value \>= 90 mmHg and change \>= 20 mmHg decrease. |
| Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days) | Following ECG parameters were analyzed: QTCF interval with criteria 450 less than (\<) value less than or equal to (\<=) 480. A standard 12-lead ECGs utilizing limb leads were collected using an ECG machine that automatically calculated the heart rate and measures PR, QT, and QTc intervals and QRS complex. On Day 1 at -1 hour (h), -0.5h, and 0h prior to the morning dose, triplicate 12-lead ECGs were obtained approximately 2 to 4 minutes apart at each time point. The average of the triplicate ECG measurements over the 3 pre dose measurement times (total of 9 ECG measurements) collected before morning dose administration on Day 1 served as each participant's baseline QTc value. |
| Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days) | Laboratory parameters assessed included: hematology (monocytes, monocytes/leukocytes) with primary criteria greater than (\>) 1.2\*upper limit of normal (ULN), clinical chemistry (bilirubin, direct bilirubin and indirect bilirubin with primary criteria \>1.5\*ULN, alanine aminotransferase with primary criteria \>3.0\*ULN, creatine kinase with primary criteria \>2.0\*ULN, urobilinogen with primary criteria greater than or equal to (\>=)1, cholesterol and triglycerides-fasting with primary criteria \>1.3\*ULN), urinalysis (ketones and urine hemoglobin with primary criteria \>=1). |
| Part A: Renal Clearance (CLr) of PF-07258669 | Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14 | Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau). |
Countries
Belgium
Participant flow
Recruitment details
This study consisted of two parts: Part A and Part B. A total of 120 participants were enrolled in the study.
Pre-assignment details
Part A of this study was placebo-controlled evaluation of safety, tolerability, and PK of PF-07258669 after multiple ascending oral doses to healthy adult participants under 3 different dietary allocations: standard, high-carbohydrate high-calorie (HCHC), and high-fat, high-calorie (HFHC) diets. Part B was a 2-period, fixed-sequence, multiple-dose design to evaluate the effect of PF-07258669 on midazolam PK in healthy adult participants.
Participants by arm
| Arm | Count |
|---|---|
| Placebo: 18-60 Years (HC-HC Diet) Healthy non-Japanese participants aged 18-60 years who were on high carbohydrate-high calorie (HC-HC) diet, received placebo matched to PF-07258669 tablets orally, every eight hours (Q8H) for 14 consecutive days (only a single morning dose administered on Day 14). | 6 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) Healthy non-Japanese participants aged 18-60 years who were on HC-HC diet, received PF-07258669 2 milligrams (mg) tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 8 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) Healthy non-Japanese participants aged 18-60 years who were on HC-HC diet, received oral PF-07258669 3 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 8 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) Healthy non-Japanese participants aged 18-60 years who were on HC-HC diet, received PF-07258669 6 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 7 |
| Placebo: 18-60 Years (Standard Diet) Healthy non-Japanese participants aged 18-60 years who were on standard diet, received placebo matched to PF-07258669 tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 10 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) Healthy non-Japanese participants aged 18-60 years who were on standard diet, received PF-07258669 6 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 8 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) Healthy non-Japanese participants aged 18-60 years who were on standard diet, received PF-07258669 20 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 8 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) Healthy non-Japanese participants aged 18-60 years who were on standard diet, received PF-07258669 60 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 8 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) Healthy non-Japanese participants aged 18-60 years who were on standard diet, received PF-07258669 125 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 8 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) Healthy non-Japanese participants aged 18-60 years who were on standard diet, received PF-07258669 180 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 8 |
| Placebo: 18-60 Years (HF-HC Diet) Healthy participants aged 18-60 years who were on high fat-high calorie (HF-HC) diet, received placebo matched to PF-07258669 tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 12 |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) Healthy non-Japanese participants aged 18-60 years who were on HF-HC diet, received PF-07258669 180 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 12 |
| Placebo: Japanese 18-60 Years (Standard Diet) Healthy Japanese participants aged 18-60 years who were on standard diet, received placebo matched to PF-07258669 tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 1 |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) Healthy Japanese participants aged 18-60 years who were on standard diet, received PF-07258669 180 mg tablets orally, Q8H for 14 consecutive days (only a single morning dose administered on Day 14). | 5 |
| Midazolam Then PF-07258669 + Midazolam: Standard Diet Healthy non-Japanese participants aged 18-60 years who were on standard diet, received midazolam 1 milligram (mg) oral solution on Day 1 of Period 1 and then oral PF-07258669 180 mg tablets, Q8H from Day 1 to Day 10 of Period 2. On Days 2 and 10 of Period 2, participants received midazolam 1 mg oral solution. | 11 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part A (18 Days) | Adverse Event | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Part B- Period 2 (8 Days) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Placebo: 18-60 Years (Standard Diet) | PF-07258669 6 mg: 18-60 Years (Standard Diet) | PF-07258669 20 mg: 18-60 Years (Standard Diet) | PF-07258669 60 mg: 18-60 Years (Standard Diet) | PF-07258669 125 mg: 18-60 Years (Standard Diet) | Placebo: 18-60 Years (HC-HC Diet) | PF-07258669 180 mg: 18-60 Years (Standard Diet) | Placebo: 18-60 Years (HF-HC Diet) | PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Placebo: Japanese 18-60 Years (Standard Diet) | PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Midazolam Then PF-07258669 + Midazolam: Standard Diet | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 Years | 7 Participants | 7 Participants | 6 Participants | 7 Participants | 6 Participants | 5 Participants | 5 Participants | 6 Participants | 2 Participants | 7 Participants | 10 Participants | 10 Participants | 0 Participants | 5 Participants | 9 Participants | 92 Participants |
| Age, Customized 45-64 Years | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 27 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 | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 7 Participants | 6 Participants | 10 Participants | 8 Participants | 8 Participants | 7 Participants | 5 Participants | 6 Participants | 8 Participants | 11 Participants | 12 Participants | 0 Participants | 5 Participants | 10 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 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 |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 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 | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 6 Participants | 7 Participants | 8 Participants | 6 Participants | 8 Participants | 7 Participants | 6 Participants | 7 Participants | 7 Participants | 11 Participants | 0 Participants | 0 Participants | 10 Participants | 97 Participants |
| Sex/Gender, Customized Female | 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 | 1 Participants |
| Sex/Gender, Customized Male | 8 Participants | 8 Participants | 7 Participants | 10 Participants | 8 Participants | 8 Participants | 8 Participants | 7 Participants | 6 Participants | 8 Participants | 12 Participants | 12 Participants | 0 Participants | 5 Participants | 11 Participants | 118 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 | 0 Participants | 1 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 12 | 0 / 1 | 0 / 5 | 0 / 11 | 0 / 11 | 0 / 9 |
| other Total, other adverse events | 5 / 6 | 8 / 8 | 6 / 8 | 6 / 7 | 9 / 10 | 6 / 8 | 7 / 8 | 4 / 8 | 7 / 8 | 8 / 8 | 8 / 12 | 10 / 12 | 0 / 1 | 3 / 5 | 2 / 11 | 8 / 11 | 2 / 9 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 1 / 8 | 0 / 7 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 12 | 0 / 1 | 0 / 5 | 0 / 11 | 0 / 11 | 0 / 9 |
Outcome results
Primary
Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
ECG criteria: QTc corrected using Fridericia's formula (QTCF) interval aggregate in milliseconds (msec): less than or equal to (\<=) change \<= 60 msec. Baseline was defined as the average of the triplicate ECG measurements over the 3 pre-dose measurement times (-1 hour, -0.5 hour, and pre-dose 0 hour; total of 9 ECG measurements) on Day 1.
Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 1 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 1 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
Primary
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by clinical research unit (CRU) staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Time frame: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day at Screening | 0 Participants |
Primary
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Time frame: Part A: Day -1 (1 day prior to dosing)
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day -1 | 0 Participants |
Primary
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Time frame: Part A: Day 14
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 14 | 0 Participants |
Primary
Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7
All fluids consumed by the participants between 0 to 24 hours on days requiring 24-hour fluid intake assessments were recorded by CRU staff. The cumulative fluid intake for the 24-hour period was measured and recorded. Participants were instructed to void urine to empty their bladder at 0 hours. All urine voided after this time was collected up to, and including, a final void of urine at 24 hours.
Time frame: Part A: Day 7
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With 24-Hour Fluid Intake and Urine Output >6 Liters Per Day on Day 7 | 0 Participants |
Primary
Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
Vital signs included: a) supine systolic blood pressure (SBP): change greater than or equal to (\>=) 30 millimeters of mercury (mmHg) increase, postural difference (supine standing) \>= 20 mmHg, standing systolic SBP (mmHg) less than (\<) 90 mmHg, \>= 160 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; b) supine diastolic blood pressure (DBP) \< 50 mmHg, \>= 90 mmHg, change \>= 20 mmHg increase, change \>= 20mmHg decrease; postural difference (supine standing) \>= 10 mmHg; standing \<50 mmHg, value \>=90 mmHg, change \>=20 mmHg increase, change \>=20 mmHg decrease, C) standing pulse rate (PR) greater than (\>) 140 bpm. Baseline for supine BP and pulse rate was defined as the average of the triplicate measurements collected at the pre-dose (0 hour) assessment on Day 1. Baseline for standing BP, standing pulse rate, respiratory rate and oral body temperature were defined as the pre-dose (0 hour) assessment on Day 1.
Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 1 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 1 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 2 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 1 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 1 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 1 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 4 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 1 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 1 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 3 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 1 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 1 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 1 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 1 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 1 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 1 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 1 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 3 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 1 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 1 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 1 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 1 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 1 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 2 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 1 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 1 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 2 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 1 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 1 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 3 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 2 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 1 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 1 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 1 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 1 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 1 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 1 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 2 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 2 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 1 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 1 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 3 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 2 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 3 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 3 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 2 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 1 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 1 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value < 50 mmHg | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value < 50 mmHg | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing PR >140 bpm | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine SBP Change >= 30mmHg increase | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | SBP postural difference >=20mmHg | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 30 mmHg increase | 1 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP change >= 20 mmHg increase | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value >= 160 mmHg | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic BP change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing SBP Value < 90 mmHg | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Supine DBP value >= 90 mmHg | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | DBP (mmHg) postural difference (supine standing) | 0 Participants |
Primary
Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
Laboratory assessments included clinical chemistry, hematology, and urinalysis. Abnormality was determined based on the criteria specified in the sponsor reporting standards. The primary criteria was less than (\<) 0.8\* lower limit of normal (LLN) for lymphocytes and lymphocytes/leukocytes, greater than (\>) 1.2\* upper limit of normal (ULN) for lymphocytes, eosinophils/leukocytes, monocytes, and monocytes/leukocytes; greater than (\>) 3.0\* ULN for alanine aminotransferase, \>1.3\* ULN for urea nitrogen, cholesterol, and triglycerides; \>1.030 for specific gravity (scalar), greater than or equal to (\>=) 1 for ketones, urine protein, urine hemoglobin, urine bilirubin, leukocyte esterase.
Time frame: Part A: Baseline to maximum up to 10 days after administration of the final dose of study intervention (maximum up to 24 days)
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 5 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 6 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 6 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 6 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 9 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 5 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 8 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 7 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 8 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 4 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 11 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 8 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 1 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 3 Participants |
Primary
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported.
Time frame: Part A: At Screening (Day-28 [28 days prior to dosing] to Day -3 [3 days prior to dosing])
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 1 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 1 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) at Screening | 0 Participants |
Primary
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported.
Time frame: Part A: Day 14
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 14 | 0 Participants |
Primary
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported.
Time frame: Part A: On Day -2 (2 days prior to dosing)
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day -2 | 0 Participants |
Primary
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported.
Time frame: Part A: Day 21
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 21 | 0 Participants |
Primary
Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7
C-SSRS is interview-based rating scale to assess suicidal ideation and behavior. C-SSRS was mapped to Columbia-Classification Algorithm of Suicide Assessment(C-CASA) and suicidal behavior events were scored as follows:1.Completed suicide,2.Suicide attempt,3.Interrupted attempt,4.Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors. Participants with response Yes to items 4,5 or behavioral question of C-SSRS were assessed by clinician and had their suicidality managed. Suicidal behaviors were scored as1.Completed suicide response Yes on Completed Suicide,2.Suicide attempt had response Yes on Actual Attempt,3.Interrupted attempt, had response Yes on Interrupted attempt,4.Aborted attempt, had response Yes on Aborted attempt,5.Preparatory actions toward imminent suicidal behaviors, had response Yes on Preparatory Acts or Behavior.Here, number of participants with positive response (response of yes) to suicidal behavior or ideation were reported.
Time frame: Part A: On Day 7
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Positive Response on Columbia Suicide Severity Rating Scale (C-SSRS) on Day 7 | 0 Participants |
Primary
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study intervention and up to 35 days after last dose of study intervention that were absent before treatment or that worsened after treatment.
Time frame: Part A: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 49 days)
Population: The safety analysis set for Part A included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part A.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Placebo: 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 9 Participants |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| Placebo: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| PF-07258669 180 mg: 18-60 Years (HF-HC Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 10 Participants |
| Placebo: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 0 Participants |
| PF-07258669 180 mg: Japanese 18-60 Years (Standard Diet) | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
Primary
Part B: Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam Alone on Day 1 of Period 1
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Time frame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Area Under the Plasma Concentration-Time Curve From Time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam Alone on Day 1 of Period 1 | 19.35 Nanogram*hour per milliliter | Geometric Coefficient of Variation 48 |
Primary
Part B: Area Under the Plasma Concentration-Time Curve From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam Alone on Day 1 of Period 1
AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Time frame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Area Under the Plasma Concentration-Time Curve From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam Alone on Day 1 of Period 1 | 18.56 Nanogram*hour per milliliter | Geometric Coefficient of Variation 47 |
Primary
Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Time frame: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 | 41.16 Nanogram*hour per milliliter | Geometric Coefficient of Variation 34 |
Primary
Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
AUCinf was defined as the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: AUCinf of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 | 32.84 Nanogram*hour per milliliter | Geometric Coefficient of Variation 32 |
Primary
Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Time frame: Part B/ Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 | 40.41 Nanogram*hour per milliliter | Geometric Coefficient of Variation 33 |
Primary
Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
AUClast was defined as the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: AUClast of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 | 30.27 Nanogram*hour per milliliter | Geometric Coefficient of Variation 35 |
Primary
Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 10 of Period 2
Cmax was defined as the maximum observed plasma concentration.
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 10
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 10 of Period 2 | 11.73 Nanogram per milliliter | Geometric Coefficient of Variation 30 |
Primary
Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 2 of Period 2
Cmax is the maximum observed plasma concentration.
Time frame: Part B/Period 2: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 2
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Cmax of Midazolam in Combination With PF-07258669 on Day 2 of Period 2 | 10.83 Nanogram per milliliter | Geometric Coefficient of Variation 27 |
Primary
Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone on Day 1 of Period 1
Cmax was defined as the maximum observed plasma concentration.
Time frame: Part B/Period 1: 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours post-dose on Day 1
Population: Pharmacokinetic (PK) parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and had at least one of the PK parameters of interest calculated, for Part B of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone on Day 1 of Period 1 | 6.213 Nanogram per milliliter | Geometric Coefficient of Variation 43 |
Secondary
Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Aetau was defined as the amount of unchanged drug recovered in urine during the dosing interval.
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Population: PK analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.004304 Milligrams | Geometric Coefficient of Variation 45 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.004490 Milligrams | Geometric Coefficient of Variation 153 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.01690 Milligrams | Geometric Coefficient of Variation 34 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.01462 Milligrams | Geometric Coefficient of Variation 49 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.04039 Milligrams | Geometric Coefficient of Variation 70 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.1440 Milligrams | Geometric Coefficient of Variation 43 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.3173 Milligrams | Geometric Coefficient of Variation 109 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.3371 Milligrams | Geometric Coefficient of Variation 188 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.3146 Milligrams | Geometric Coefficient of Variation 314 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Amount of PF-0728669 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau) | 0.6581 Milligrams | Geometric Coefficient of Variation 37 |
Secondary
Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14
Area under the plasma concentration-time profile from time zero to time tau, the dosing interval, where tau = 8 hours.
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
Population: PK analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 46.27 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 26 |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 62.40 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 32 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 60.42 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 27 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 76.25 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 30 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 113.6 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 15 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 162.0 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 28 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 107.2 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 42 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 147.0 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 45 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 480.4 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 28 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 388.1 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 38 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 1795 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 26 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 1207 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 26 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 3946 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 28 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 2597 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 29 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 3357 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 34 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 5313 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 31 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 3361 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 27 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 5845 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 19 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 1 | 3331 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 13 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (Tau) (AUCtau) of PF-07258669 on Days 1 and 14 | Day 14 | 6074 Nanograms*hours per (/) milliliter | Geometric Coefficient of Variation 21 |
Secondary
Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 1 and Day 14
Population: PK analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 23.16 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 26 |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 31.21 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 32 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 20.15 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 27 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 25.44 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 30 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 18.93 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 15 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 27.01 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 28 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 17.87 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 42 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 24.47 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 45 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 24.04 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 28 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 19.42 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 38 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 29.90 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 26 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 20.14 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 26 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 31.57 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 28 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 20.75 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 29 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 18.64 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 34 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 29.49 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 31 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 18.67 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 27 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 32.49 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 19 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 1 | 18.52 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 13 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Area Under the Curve From Time 0 to Dosing Interval (Tau) (AUCtau, dn) of PF-07258669 on Days 1 and 14 | Day 14 | 33.74 Nanograms*hours/ milliliter/ milligrams | Geometric Coefficient of Variation 21 |
Secondary
Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14
Cmax was defined maximum observed serum concentration. Cmax (dn) was calculated as Cmax/dose.
Time frame: Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14
Population: PK analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 9.742 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 25 |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 10.99 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 22 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 8.352 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 22 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 9.301 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 25 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 8.403 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 22 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 9.952 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 29 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 7.666 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 47 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 9.515 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 39 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 8.269 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 25 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 6.562 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 32 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 9.473 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 26 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 7.803 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 27 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 9.982 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 25 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 7.899 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 28 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 7.013 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 37 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 8.134 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 22 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 6.770 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 42 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 9.849 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 19 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 1 | 6.719 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 9 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax,dn) of PF-07258669 on Days 1 and 14 | Day 14 | 9.723 Nanograms per milliliter per milligram | Geometric Coefficient of Variation 26 |
Secondary
Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14
Cmax was defined as the maximum plasma concentration.
Time frame: Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14
Population: PK parameter set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 19.47 Nanogram per milliliter | Geometric Coefficient of Variation 25 |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 21.96 Nanogram per milliliter | Geometric Coefficient of Variation 21 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 25.06 Nanogram per milliliter | Geometric Coefficient of Variation 22 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 27.91 Nanogram per milliliter | Geometric Coefficient of Variation 25 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 50.41 Nanogram per milliliter | Geometric Coefficient of Variation 22 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 59.76 Nanogram per milliliter | Geometric Coefficient of Variation 29 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 45.99 Nanogram per milliliter | Geometric Coefficient of Variation 47 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 57.08 Nanogram per milliliter | Geometric Coefficient of Variation 39 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 165.2 Nanogram per milliliter | Geometric Coefficient of Variation 25 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 131.2 Nanogram per milliliter | Geometric Coefficient of Variation 32 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 568.5 Nanogram per milliliter | Geometric Coefficient of Variation 26 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 468.3 Nanogram per milliliter | Geometric Coefficient of Variation 27 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1246 Nanogram per milliliter | Geometric Coefficient of Variation 25 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 987.2 Nanogram per milliliter | Geometric Coefficient of Variation 28 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1263 Nanogram per milliliter | Geometric Coefficient of Variation 37 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1464 Nanogram per milliliter | Geometric Coefficient of Variation 21 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1218 Nanogram per milliliter | Geometric Coefficient of Variation 42 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1772 Nanogram per milliliter | Geometric Coefficient of Variation 19 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1210 Nanogram per milliliter | Geometric Coefficient of Variation 9 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1750 Nanogram per milliliter | Geometric Coefficient of Variation 26 |
Secondary
Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
Aetau% was defined as the percentage of dose recovered in urine as unchanged drug.
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Population: PK analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.2152 Percentage of dose | Geometric Coefficient of Variation 45 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.1496 Percentage of dose | Geometric Coefficient of Variation 153 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.2814 Percentage of dose | Geometric Coefficient of Variation 34 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.2436 Percentage of dose | Geometric Coefficient of Variation 49 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.2020 Percentage of dose | Geometric Coefficient of Variation 70 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.2400 Percentage of dose | Geometric Coefficient of Variation 43 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.2536 Percentage of dose | Geometric Coefficient of Variation 109 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.1872 Percentage of dose | Geometric Coefficient of Variation 189 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.1748 Percentage of dose | Geometric Coefficient of Variation 314 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Percentage Dose of PF-07258669 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%) | 0.3654 Percentage of dose | Geometric Coefficient of Variation 37 |
Secondary
Part A: Renal Clearance (CLr) of PF-07258669
Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau).
Time frame: Part A: 0 to 8, 8 to 16, and 16 to 24 hours post dose on Day 14
Population: PK analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.06896 Liter/ hour | Geometric Coefficient of Variation 37 |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.05887 Liter/ hour | Geometric Coefficient of Variation 171 |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.1042 Liter/ hour | Geometric Coefficient of Variation 44 |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.09946 Liter/ hour | Geometric Coefficient of Variation 33 |
| Placebo: 18-60 Years (Standard Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.08412 Liter/ hour | Geometric Coefficient of Variation 48 |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.08026 Liter/ hour | Geometric Coefficient of Variation 55 |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.08040 Liter/ hour | Geometric Coefficient of Variation 116 |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.06341 Liter/ hour | Geometric Coefficient of Variation 241 |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.05381 Liter/ hour | Geometric Coefficient of Variation 350 |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Renal Clearance (CLr) of PF-07258669 | 0.1083 Liter/ hour | Geometric Coefficient of Variation 31 |
Secondary
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14
Tmax was defined as the time taken (in hours) to reach the maximum plasma drug concentration.
Time frame: Part A: 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose on Day 1 and Day 14
Population: PK analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of midazolam and/or study intervention and had at least one of the PK parameters of interest calculated, for part A of the study. Here, 'Number Analyzed' signifies participants evaluable for the specified rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.010 Hours |
| Placebo: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1.000 Hours |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1.000 Hours |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.000 Hours |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 0.5830 Hours |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 0.7415 Hours |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 0.8265 Hours |
| PF-07258669 6 mg: 18-60 Years (HC-HC Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 0.7665 Hours |
| Placebo: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.000 Hours |
| Placebo: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1.010 Hours |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.000 Hours |
| PF-07258669 6 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1.000 Hours |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.000 Hours |
| PF-07258669 20 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1.000 Hours |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1.000 Hours |
| PF-07258669 60 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.500 Hours |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 1.000 Hours |
| PF-07258669 125 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.000 Hours |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 1 | 0.5830 Hours |
| PF-07258669 180 mg: 18-60 Years (Standard Diet) | Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07258669 on Days 1 and 14 | Day 14 | 1.000 Hours |
Secondary
Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria
Following ECG parameters were analyzed: QTCF interval with criteria 450 less than (\<) value less than or equal to (\<=) 480. A standard 12-lead ECGs utilizing limb leads were collected using an ECG machine that automatically calculated the heart rate and measures PR, QT, and QTc intervals and QRS complex. On Day 1 at -1 hour (h), -0.5h, and 0h prior to the morning dose, triplicate 12-lead ECGs were obtained approximately 2 to 4 minutes apart at each time point. The average of the triplicate ECG measurements over the 3 pre dose measurement times (total of 9 ECG measurements) collected before morning dose administration on Day 1 served as each participant's baseline QTc value.
Time frame: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
Population: The safety analysis set for Part B included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 0 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants Who Met Defined Electrocardiogram (ECG) Criteria | 1 Participants |
Secondary
Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data
Vital signs examination included: supine systolic blood pressure with criteria change \>= 30 mmHg decrease, supine diastolic blood pressure with criteria value \>= 90 mmHg and change \>= 20 mmHg decrease.
Time frame: Part B: Day 1 of Period 1 up to Day 10 of Period 2 (12 days)
Population: The safety analysis set for Part B included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part B.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic blood pressure: value >= 90 mmHg | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing systolic blood pressure | 0 Participants |
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic blood pressure: value change >= 20 mmHg decrease | 0 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic blood pressure: value >= 90 mmHg | 1 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing systolic blood pressure | 1 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic blood pressure: value change >= 20 mmHg decrease | 2 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing systolic blood pressure | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic blood pressure: value change >= 20 mmHg decrease | 1 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Categorical Summary of Post-Baseline Vital Signs Data | Standing diastolic blood pressure: value >= 90 mmHg | 1 Participants |
Secondary
Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality
Laboratory parameters assessed included: hematology (monocytes, monocytes/leukocytes) with primary criteria greater than (\>) 1.2\*upper limit of normal (ULN), clinical chemistry (bilirubin, direct bilirubin and indirect bilirubin with primary criteria \>1.5\*ULN, alanine aminotransferase with primary criteria \>3.0\*ULN, creatine kinase with primary criteria \>2.0\*ULN, urobilinogen with primary criteria greater than or equal to (\>=)1, cholesterol and triglycerides-fasting with primary criteria \>1.3\*ULN), urinalysis (ketones and urine hemoglobin with primary criteria \>=1).
Time frame: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)
Population: The safety analysis set for Part B included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 2 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 4 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality | 4 Participants |
Secondary
Part B: Number of Participants With TEAEs
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment.
Time frame: Part B: Day 1 to maximum up to 35 days after administration of the final dose of study intervention (maximum up to 46 days)
Population: The safety analysis set for Part B included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention in Part B.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With TEAEs | 2 Participants |
| PF-07258669 2 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With TEAEs | 8 Participants |
| PF-07258669 3 mg: 18-60 Years (HC-HC Diet) | Part B: Number of Participants With TEAEs | 2 Participants |