Healthy Participants
Conditions
Keywords
Food effect study
Brief summary
The purpose of the study is to evaluate the effect of a low-fat and high-fat meal on the medicine called PF-07284890 following three single doses PF-07284890. The study will include male participants and female participants of non-childbearing potential who are healthy. Participants will be required to stay in the clinical research unit for 15 days and 14 nights.
Interventions
DRUGPF-07284890 Treatment A
PF-07284890 tablet by mouth while fasting
DRUGPF-07284890 Treatment B
PF-07284890 tablet after low fat meal
DRUGPF-07284890 Treatment C
PF-07284890 tablet after high fat meal
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Females of non-childbearing potential and males who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and 12-lead ECGs. * Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
Exclusion criteria
* Evidence or history of clinically significant uveitis, 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), including any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). * 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 Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1 and 2 | AUClast was defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was determined by linear/Log trapezoidal method. |
| Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1 and 2 | AUCinf was defined as area under the plasma concentration-time curve from time zero extrapolated to infinity. AUCinf = AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. |
| Maximum Observed Concentration (Cmax) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1 and 2 | Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data. |
| AUClast of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3 | AUClast was defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was determined by linear/Log trapezoidal method. |
| AUCinf of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3 | AUCinf was defined as area under the plasma concentration-time curve from time zero extrapolated to infinity. AUCinf = AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. |
| Cmax of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3 | Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks | Supine systolic/diastolic blood pressure (BP) and pulse rate (PR) were measured and evaluated against pre-specified categorization criteria. The criteria included change of supine systolic/diastolic BP \>=30 mmHg increase or decrease, and value of supine PR \>120 beats per minute (bpm). |
| Time to Reach Cmax (Tmax) of PF-07284890 in Plasma | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3 | Tmax was defined as time to reach maximum observed plasma concentration. The determination method of Tmax was observing directly from data as time of first occurrence. |
| Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks | Standard 12-lead ECGs utilizing limb leads were collected using an ECG machine that automatically calculated the heart rate (HR) and measured PR interval, QT interval, corrected QT interval using Fridericia's formula (QTcF), and time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS) complex. The number of participants with PR/QRS values and percent change from baseline, QT interval values, and QTcF values and increases from baseline in the pre-specified categories were summarized in this outcome measure (OM). |
| Terminal Elimination Half-Life (t1/2) of PF-07284890 in Plasma | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3 | t1/2 was defined as the time required for the plasma concentration to decline by 50% during the elimination phase. t1/2 = loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. |
| Apparent Clearance (CL/F) of PF-07284890 in Plasma | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3 | CL/F was defined as the apparent clearance. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL/F = dose/AUCinf, where AUCinf was the area under the plasma concentration-time curve from time zero extrapolated to infinity. |
| Apparent Volume of Distribution for Extravascular Dosing (Vz/F) of PF-07284890 in Plasma | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3 | Vz/F was defined as the apparent volume of distribution for extravascular dosing. Determination method of Vz/F was dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. |
| Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) | From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks | An AE was defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any events occurring following start of treatment were considered as TEAEs. |
| Number of Participants With Clinical Laboratory Abnormalities | From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks | The hematological (Lymphocytes/Leukocytes, Neutrophils/Leukocytes and Monocytes/Leukocytes), clinical chemistry (Urate and Potassium) and urinalysis (Urine Hemoglobin, Leukocyte Esterase and Bacteria) safety tests were assessed against the pre-specified criteria. The assessment did not take into account whether each participant's baseline test result was within or outside the laboratory reference range for the particular laboratory parameter. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Female The Female participant was a healthy adult of non-childbearing potential between 18-65 years of age. | 1 |
| Male Male participants were healthy adults between 18-65 years of age. | 11 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 (5 Days) | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Female | Male | Total |
|---|---|---|---|
| Age, Continuous | 57.0 Years | 42.5 Years STANDARD_DEVIATION 12.23 | 43.8 Years STANDARD_DEVIATION 12.38 |
| Age, Customized 18-25 | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized 26-35 | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized 36-45 | 0 Participants | 6 Participants | 6 Participants |
| Age, Customized >45 | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 10 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 11 Participants | 11 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 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 2 / 6 | 1 / 6 | 2 / 6 | 3 / 6 | 1 / 5 | 1 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition
AUCinf was defined as area under the plasma concentration-time curve from time zero extrapolated to infinity. AUCinf = AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1 and 2
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 29380 ng*hr/mL | Geometric Coefficient of Variation 25 |
| PF-07284890 200 mg Fasted (Reference) | Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 24600 ng*hr/mL | Geometric Coefficient of Variation 46 |
90% CI: [97.91, 137.95]
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition
AUClast was defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was determined by linear/Log trapezoidal method.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1 and 2
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 28270 Nanogram*Hour per Milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| PF-07284890 200 mg Fasted (Reference) | Area Under the Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 23510 Nanogram*Hour per Milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
90% CI: [109.76, 131.75]
Primary
AUCinf of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition
AUCinf was defined as area under the plasma concentration-time curve from time zero extrapolated to infinity. AUCinf = AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | AUCinf of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 34130 ng*hr/mL | Geometric Coefficient of Variation 20 |
| PF-07284890 200 mg Fasted (Reference) | AUCinf of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 24600 ng*hr/mL | Geometric Coefficient of Variation 46 |
90% CI: [106.11, 180.41]
Primary
AUClast of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition
AUClast was defined as area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast). AUClast was determined by linear/Log trapezoidal method.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | AUClast of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 31300 ng*hr/mL | Geometric Coefficient of Variation 21 |
| PF-07284890 200 mg Fasted (Reference) | AUClast of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 23510 ng*hr/mL | Geometric Coefficient of Variation 38 |
90% CI: [114.36, 161.19]
Primary
Cmax of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition
Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 concentration value could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Cmax of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 3892 ng/mL | Geometric Coefficient of Variation 22 |
| PF-07284890 200 mg Fasted (Reference) | Cmax of PF-07284890 in Plasma, Comparison of High-Fat Meal With Fasted Condition | 1672 ng/mL | Geometric Coefficient of Variation 43 |
90% CI: [190.12, 294.38]
Primary
Maximum Observed Concentration (Cmax) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition
Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1 and 2
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 concentration value could be reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Maximum Observed Concentration (Cmax) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 3460 Nanogram per Milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| PF-07284890 200 mg Fasted (Reference) | Maximum Observed Concentration (Cmax) of PF-07284890 in Plasma, Comparison of Low-Fat Meal With Fasted Condition | 1672 Nanogram per Milliliter (ng/mL) | Geometric Coefficient of Variation 43 |
90% CI: [171.14, 250.15]
Secondary
Apparent Clearance (CL/F) of PF-07284890 in Plasma
CL/F was defined as the apparent clearance. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes). CL/F = dose/AUCinf, where AUCinf was the area under the plasma concentration-time curve from time zero extrapolated to infinity.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Apparent Clearance (CL/F) of PF-07284890 in Plasma | 8.130 Liter per Hour (L/hr) | Geometric Coefficient of Variation 46 |
| PF-07284890 200 mg Fasted (Reference) | Apparent Clearance (CL/F) of PF-07284890 in Plasma | 6.810 Liter per Hour (L/hr) | Geometric Coefficient of Variation 25 |
| PF-07284890 200 mg High-fat Meal | Apparent Clearance (CL/F) of PF-07284890 in Plasma | 5.860 Liter per Hour (L/hr) | Geometric Coefficient of Variation 20 |
Secondary
Apparent Volume of Distribution for Extravascular Dosing (Vz/F) of PF-07284890 in Plasma
Vz/F was defined as the apparent volume of distribution for extravascular dosing. Determination method of Vz/F was dose/(AUCinf\*kel), where kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Apparent Volume of Distribution for Extravascular Dosing (Vz/F) of PF-07284890 in Plasma | 186.4 Liter (L) | Geometric Coefficient of Variation 36 |
| PF-07284890 200 mg Fasted (Reference) | Apparent Volume of Distribution for Extravascular Dosing (Vz/F) of PF-07284890 in Plasma | 168.5 Liter (L) | Geometric Coefficient of Variation 30 |
| PF-07284890 200 mg High-fat Meal | Apparent Volume of Distribution for Extravascular Dosing (Vz/F) of PF-07284890 in Plasma | 132.9 Liter (L) | Geometric Coefficient of Variation 12 |
Secondary
Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Any events occurring following start of treatment were considered as TEAEs.
Time frame: From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks
Population: The analysis population included all participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) | 5 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
Number of Participants With Clinical Laboratory Abnormalities
The hematological (Lymphocytes/Leukocytes, Neutrophils/Leukocytes and Monocytes/Leukocytes), clinical chemistry (Urate and Potassium) and urinalysis (Urine Hemoglobin, Leukocyte Esterase and Bacteria) safety tests were assessed against the pre-specified criteria. The assessment did not take into account whether each participant's baseline test result was within or outside the laboratory reference range for the particular laboratory parameter.
Time frame: From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks
Population: The analysis population included all participants assigned to study intervention and who took at least 1 dose of study intervention. Number of Participants Analyzed = number of participants evaluable for laboratory abnormalities. Number Analyzed = total number of participants with at least one observation of the given laboratory test.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes/Leukocytes >1.2 x upper limit of normal (ULN) | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Neutrophils/Leukocytes <0.8 x lower limit of normal (LLN) | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Monocytes/Leukocytes >1.2 x ULN | 1 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Urate >1.2 x ULN | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Potassium >1.1 x ULN | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Urine Hemoglobin >=1 | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Clinical Laboratory Abnormalities | Bacteria >20 | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Monocytes/Leukocytes >1.2 x ULN | 1 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Bacteria >20 | 1 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Urate >1.2 x ULN | 1 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Leukocyte Esterase >=1 | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Potassium >1.1 x ULN | 1 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Urine Hemoglobin >=1 | 1 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes/Leukocytes >1.2 x upper limit of normal (ULN) | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Clinical Laboratory Abnormalities | Neutrophils/Leukocytes <0.8 x lower limit of normal (LLN) | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Neutrophils/Leukocytes <0.8 x lower limit of normal (LLN) | 1 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Bacteria >20 | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Lymphocytes/Leukocytes >1.2 x upper limit of normal (ULN) | 1 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Urate >1.2 x ULN | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Urine Hemoglobin >=1 | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Monocytes/Leukocytes >1.2 x ULN | 1 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Potassium >1.1 x ULN | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Clinical Laboratory Abnormalities | Leukocyte Esterase >=1 | 1 Participants |
Secondary
Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs)
Standard 12-lead ECGs utilizing limb leads were collected using an ECG machine that automatically calculated the heart rate (HR) and measured PR interval, QT interval, corrected QT interval using Fridericia's formula (QTcF), and time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS) complex. The number of participants with PR/QRS values and percent change from baseline, QT interval values, and QTcF values and increases from baseline in the pre-specified categories were summarized in this outcome measure (OM).
Time frame: From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks
Population: The analysis population included all participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of PR Interval >=300 msec | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Percent Change of PR Interval >=25/50% | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QRS Duration >=140 msec | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Percent Change of QRS Duration >=50% | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QT Interval >=500 msec | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >450 msec and <=480 msec | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >480 msec and <=500 msec | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >500 msec | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Change of QTcF >=30 msec and <=60 msec | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Change of QTcF >60 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Change of QTcF >=30 msec and <=60 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of PR Interval >=300 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >450 msec and <=480 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QT Interval >=500 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Percent Change of PR Interval >=25/50% | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Change of QTcF >60 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >500 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QRS Duration >=140 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >480 msec and <=500 msec | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Percent Change of QRS Duration >=50% | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >500 msec | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Percent Change of QRS Duration >=50% | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QT Interval >=500 msec | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >450 msec and <=480 msec | 1 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Change of QTcF >=30 msec and <=60 msec | 2 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QTcF >480 msec and <=500 msec | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of PR Interval >=300 msec | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Change of QTcF >60 msec | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Percent Change of PR Interval >=25/50% | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for 12-Lead Electrocardiograms (ECGs) | Value of QRS Duration >=140 msec | 0 Participants |
Secondary
Number of Participants With Pre-Specified Categorization Criteria for Vital Signs
Supine systolic/diastolic blood pressure (BP) and pulse rate (PR) were measured and evaluated against pre-specified categorization criteria. The criteria included change of supine systolic/diastolic BP \>=30 mmHg increase or decrease, and value of supine PR \>120 beats per minute (bpm).
Time frame: From baseline up to 35 days after last dose of PF-07284890, up to 11 weeks
Population: The analysis population included all participants assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Systolic BP >=30 mmHg Increase | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Diastolic BP >=20 mmHg Decrease | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Diastolic BP >=20 mmHg Increase | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Value of Supine PR >120 bpm | 0 Participants |
| PF-07284890 200 mg Low-fat Meal (Test) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Systolic BP >=30 mmHg Decrease | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Value of Supine PR >120 bpm | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Systolic BP >=30 mmHg Increase | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Systolic BP >=30 mmHg Decrease | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Diastolic BP >=20 mmHg Increase | 0 Participants |
| PF-07284890 200 mg Fasted (Reference) | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Diastolic BP >=20 mmHg Decrease | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Systolic BP >=30 mmHg Decrease | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Value of Supine PR >120 bpm | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Diastolic BP >=20 mmHg Decrease | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Systolic BP >=30 mmHg Increase | 0 Participants |
| PF-07284890 200 mg High-fat Meal | Number of Participants With Pre-Specified Categorization Criteria for Vital Signs | Change of Supine Diastolic BP >=20 mmHg Increase | 0 Participants |
Secondary
Terminal Elimination Half-Life (t1/2) of PF-07284890 in Plasma
t1/2 was defined as the time required for the plasma concentration to decline by 50% during the elimination phase. t1/2 = loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported. Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Terminal Elimination Half-Life (t1/2) of PF-07284890 in Plasma | 16.36 hr | Standard Deviation 4.1925 |
| PF-07284890 200 mg Fasted (Reference) | Terminal Elimination Half-Life (t1/2) of PF-07284890 in Plasma | 17.73 hr | Standard Deviation 5.2538 |
| PF-07284890 200 mg High-fat Meal | Terminal Elimination Half-Life (t1/2) of PF-07284890 in Plasma | 16.19 hr | Standard Deviation 4.4712 |
Secondary
Time to Reach Cmax (Tmax) of PF-07284890 in Plasma
Tmax was defined as time to reach maximum observed plasma concentration. The determination method of Tmax was observing directly from data as time of first occurrence.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose of PF-07284890 in Periods 1-3
Population: The analysis population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of interest could be reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-07284890 200 mg Low-fat Meal (Test) | Time to Reach Cmax (Tmax) of PF-07284890 in Plasma | 3.00 Hours (hr) |
| PF-07284890 200 mg Fasted (Reference) | Time to Reach Cmax (Tmax) of PF-07284890 in Plasma | 3.00 Hours (hr) |
| PF-07284890 200 mg High-fat Meal | Time to Reach Cmax (Tmax) of PF-07284890 in Plasma | 4.01 Hours (hr) |