Healthy
Conditions
Keywords
PF-06821497, Relative Bioavailability, Food Effect
Brief summary
The purpose of this study is to understand the effect of tablet formulation and presence of food on the study medicine PF-06821497 in healthy adult participants. The study is seeking for male and female participants who: * Are 18 years of age or more. * Are confirmed to be healthy after performing some medical and physical tests. * Weigh more than 50kgs of body weight and have a body mass index of 17 and a half kg per meter squared or more. The study consists of two parts. In each part of the study, the selected participants will take part in 3 study periods to receive 3 different treatments which are randomly assigned. There will also be a 5-day gap between each study period. This is done so that the medicine is passed out of the body before the start of next study period. Each treatment consists of a single dose of PF-06821497. The treatments differ by tablet formulation and/or whether the medicine is to be given with food or without food conditions. How the medicine is processed in the body will be studied after giving the medicines to the participants. This will be done by collecting blood samples after each administration. The results will be used to see the effect of tablet formulation and presence of food on the amount of PF-06821497 available in the blood of the participants. In each part, participants will be on the study up to 10 weeks, including the screening and follow-up periods.
Interventions
DRUGPF-06821497 Treatment A
A single dose of PF-06821497 administered under fasting conditions.
DRUGPF-06821497 Treatment B
A single dose of PF-06821497 administered under fasting conditions.
DRUGPF-06821497 Treatment C
A single dose of PF-06821497 administered under fasting conditions.
DRUGPF-06821497 Treatment D
A single dose of PF-06821497 administered under fasting conditions.
DRUGPF-06821497 Treatment E
A single dose of PF-06821497 administered after low fat meal
DRUGPF-06821497 Treatment F
A single dose of PF-06821497 administered after high fat meal.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
Open-label Study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants ≥18 years of age, inclusive, at screening. * Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and 12-lead ECGs. * BMI of ≥17.5 kg/m2; and a total body weight \>50 kg (110 lb) * Evidence of a personally signed and dated ICD indicating that the participant has been informed of all pertinent aspects of the study. * Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) or prior allergic reaction to any component of PF-06821497. * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * 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. * Previous administration with an investigational product (drug or vaccine) 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497 | Days 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose), 2 and 3 in Periods 1 to 3. | The AUCinf was determined by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. AUClast is the area under the concentration-time curve from 0 to time of last measurable concentration |
| Maximum Plasma Concentration (Cmax) for PF-06821497. | Days 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose), 2 and 3 in Periods 1 to 3. | The Cmax was observed directly from data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs). | From screening up to Day 35 | 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. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic, was considered serious. |
| Number of Participants With Laboratory Abnormalities | From screening up to Day 3 of Period 3, and prior to early termination/discontinuation, up to 10 weeks. | Safety laboratory assessments included urinalysis, hematology, chemistry and other. All the safety laboratory samples were collected following at least a 4-hour fast. |
| Number of Participants With Clinically Significant ECG Findings | From screening up to Day 3 of Period 3, and prior to early termination/discontinuation, up to 10 weeks. | Single 12-lead electrocardiogram or electrocardiography (ECG) readings were taken at approximately each test. All ECG assessments were made after at least a 5-minute rest in a supine position and prior to any blood draws or vital sign measurements. |
Countries
United States
Participant flow
Pre-assignment details
A total of 18 participants (12 participants in Part 1 and 6 participants in Part 2) were randomized and assigned to study treatments.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 In Part 1, each enrolled participant participated in 3 study periods to receive 3 different treatments(Treatment A: Single 250 mg dose (1 × 250 mg) of MST tablet formulation (Formulation 1), fasted; Treatment B: Single 250 mg dose (1 × 250 mg) of WG tablet formulation (Formulation 2), fasted; Treatment C: Single 250 mg dose (1 × 250 mg) of WG tablet formulation (larger API particle size) (Formulation 3), fasted.) according to the sequence determined by randomization with 5-day washouts between PF-06821497 administration. | 12 |
| Part 2 In Part 2, each enrolled participant participated in 3 study periods to receive 3 different treatments (Treatment D: Single 1250 mg dose (5 × 250 mg) of WG tablet formulation (Formulation 2), fasted; Treatment E: Single 1250 mg dose (5 × 250 mg) of WG tablet formulation (Formulation 2), fed, low-fat; Treatment F: Single 1250 mg dose (5 × 250 mg) of WG tablet formulation (Formulation 2), fed, high-fat.) according to the sequence determined by randomization with 5-day washouts between PF-06821497 administration. | 6 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1 | Part 2 | Total |
|---|---|---|---|
| Age, Customized 18 -44 years | 7 Participants | 2 Participants | 9 Participants |
| Age, Customized 45 - 64 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Customized >= 65 years | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American, White | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American, White, American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 7 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 5 / 12 | 4 / 12 | 2 / 12 | 3 / 6 | 3 / 6 | 2 / 5 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 6 | 0 / 6 | 1 / 5 |
Outcome results
Primary
Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497
The AUCinf was determined by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. AUClast is the area under the concentration-time curve from 0 to time of last measurable concentration
Time frame: Days 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose), 2 and 3 in Periods 1 to 3.
Population: The pharmacokinetic (PK) parameter analysis population was defined as all participants randomized and treated who had at least 1 of the PF-06821497 PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 PF-06821497 Form 1 250 mg Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497 | 3302 ng*hr/mL | Geometric Coefficient of Variation 33 |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497 | 3375 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497 | 3479 ng*hr/mL | Geometric Coefficient of Variation 39 |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497 | 11220 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497 | 22810 ng*hr/mL | Geometric Coefficient of Variation 24 |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06821497 | 25690 ng*hr/mL | Geometric Coefficient of Variation 35 |
Comparison: Part 1 PF-06821497 Form 1 250 mg Fasted was the Reference treatment and Part 1 PF-06821497 Form 3 250 mg Fasted was the Test treatment.90% CI: [100.55, 117.05]Mixed Models Analysis
Comparison: Part 1 PF-06821497 Form 3 250 mg Fasted was the Test treatment and Part 1 PF-06821497 Form 2 250 mg Fasted was the Reference treatment.90% CI: [98.39, 114.54]Mixed Models Analysis
Comparison: Part 2 PF-06821497 Form 2 1250 mg Fed High-fat was the Test treatment and Part 2 PF-06821497 Form 2 1250 mg Fasted was the Reference treatment.90% CI: [178.67, 293.48]Mixed Models Analysis
Comparison: Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat was the Test treatment and Part 2 PF-06821497 Form 2 1250 mg Fasted was the Reference treatment.90% CI: [164.41, 261.09]
Comparison: Part 1 PF-06821497 Form 1 250 mg Fasted was the Reference treatment, and Part 1 PF-06821497 Form 2 250 mg Fasted was the Test treatment90% CI: [95.55, 109.3]Mixed Models Analysis
Primary
Maximum Plasma Concentration (Cmax) for PF-06821497.
The Cmax was observed directly from data.
Time frame: Days 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose), 2 and 3 in Periods 1 to 3.
Population: The PK concentration population was defined as all participants randomized and treated who had at least 1 PF-06821497 concentration in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1 PF-06821497 Form 1 250 mg Fasted | Maximum Plasma Concentration (Cmax) for PF-06821497. | 862.6 ng/mL | Geometric Coefficient of Variation 50 |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Maximum Plasma Concentration (Cmax) for PF-06821497. | 1023 ng/mL | Geometric Coefficient of Variation 35 |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Maximum Plasma Concentration (Cmax) for PF-06821497. | 1255 ng/mL | Geometric Coefficient of Variation 37 |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Maximum Plasma Concentration (Cmax) for PF-06821497. | 2699 ng/mL | Geometric Coefficient of Variation 31 |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Maximum Plasma Concentration (Cmax) for PF-06821497. | 7685 ng/mL | Geometric Coefficient of Variation 28 |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Maximum Plasma Concentration (Cmax) for PF-06821497. | 8905 ng/mL | Geometric Coefficient of Variation 7 |
Comparison: Part 1 PF-06821497 Form 3 250 mg Fasted was the Test treatment and Part 1 PF-06821497 Form 1 250 mg Fasted was the Reference treatment.90% CI: [121.29, 174.53]Mixed Models Analysis
Comparison: Part 1 PF-06821497 Form 3 250 mg Fasted was the Test treatment and Part 1 PF-06821497 Form 2 250 mg Fasted was the Reference treatment.90% CI: [102.24, 147.12]Mixed Models Analysis
Comparison: Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat was the Test treatment and Part 2 PF-06821497 Form 2 1250 mg Fasted was the Reference treatment.90% CI: [226.39, 358.06]Mixed Models Analysis
Comparison: Part 2 PF-06821497 Form 2 1250 mg Fed High-fat was the Test treatment and Part 2 PF-06821497 Form 2 1250 mg Fasted was the Reference treatment.90% CI: [256.9, 418.44]Mixed Models Analysis
Comparison: Part 1 PF-06821497 Form 1 250 mg Fasted was the Reference treatment, and Part 1 PF-06821497 Form 2 250 mg Fasted was the Test treatment.90% CI: [96.36, 146.06]Mixed Models Analysis
Secondary
Number of Participants With Clinically Significant ECG Findings
Single 12-lead electrocardiogram or electrocardiography (ECG) readings were taken at approximately each test. All ECG assessments were made after at least a 5-minute rest in a supine position and prior to any blood draws or vital sign measurements.
Time frame: From screening up to Day 3 of Period 3, and prior to early termination/discontinuation, up to 10 weeks.
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), %Change >= 25/50% | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), value >= 140 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), %Change >= 50% | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), value > = 300 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QT Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), value >= 140 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 450 <= value < 480 | 1 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QT Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), %Change >= 25/50% | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), %Change >= 50% | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), value > = 300 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), %Change >= 25/50% | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), value > = 300 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), value >= 140 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), %Change >= 50% | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QT Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 30 <= change < 60 | 1 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QT Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), %Change >= 50% | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), value >= 140 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), value > = 300 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), %Change >= 25/50% | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), %Change >= 25/50% | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), value >= 140 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), %Change >= 50% | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), value > = 300 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QT Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), %Change >= 50% | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QRS Duration, aggregate (msec), value >= 140 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 30 <= change < 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), %Change >= 25/50% | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), 480 <= value < 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), change >= 60 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcF Interval, aggregate (msec), value >= 500 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | PR Interval, aggregate (msec), value > = 300 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QTcB Interval, aggregate (msec), 450 <= value < 480 | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Clinically Significant ECG Findings | QT Interval, aggregate (msec), value >= 500 | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
Safety laboratory assessments included urinalysis, hematology, chemistry and other. All the safety laboratory samples were collected following at least a 4-hour fast.
Time frame: From screening up to Day 3 of Period 3, and prior to early termination/discontinuation, up to 10 weeks.
Population: The analysis population included all participants randomly assigned to study intervention and who took at least one dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Laboratory Abnormalities | 0 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Laboratory Abnormalities | 0 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Laboratory Abnormalities | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Laboratory Abnormalities | 0 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Laboratory Abnormalities | 1 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Laboratory Abnormalities | 1 Participants |
Secondary
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. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth, was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic, was considered serious.
Time frame: From screening up to Day 35
Population: The safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants was analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 PF-06821497 Form 1 250 mg Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs). | 5 Participants |
| Part 1 PF-06821497 Form 2 250 mg Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs). | 4 Participants |
| Part 1 PF-06821497 Form 3 250 mg Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs). | 2 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fasted | Number of Participants With Treatment Emergent Adverse Events (TEAEs). | 3 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed Low-fat | Number of Participants With Treatment Emergent Adverse Events (TEAEs). | 3 Participants |
| Part 2 PF-06821497 Form 2 1250 mg Fed High-fat | Number of Participants With Treatment Emergent Adverse Events (TEAEs). | 2 Participants |