Healthy Participants
Conditions
Keywords
PF-07258669, first in human, melanocortin-4 receptor, MC4R, healthy participants, safety, tolerability, pharmacokinetics
Brief summary
This study will be the first time PF-07258669 is administered to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of PF-07258669 following administration of single oral doses to healthy adult participants.
Interventions
DRUGPF-07258669
PF-07258669 will be prepared as an oral solution and/or suspension given in escalating single doses to be determined
DRUGPlacebo
Matching placebo will be prepared as an oral solution and/or suspension given in each cohort
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Female participants of non-child bearing potential and male participants and who are overtly healthy as determined by medical evaluation including medical history, physical examination, neurological examination, laboratory tests, and cardiac monitoring. * 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, as appropriate. * 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 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), as well as presence of lipid panel abnormalities (eg, hypercholesterolemia, hypertriglyceridemia). * Evidence of history of orthostatic hypotension or symptomatic bradycardia. * 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 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). * Current findings or documented past history of blood pressure values \<90 mmHg systolic or \<50 mmHg diastolic. * Any lipid panel parameter (ie, total cholesterol, triglycerides, HDL, and/or LDL) ≥1.25× ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks) | The neurological exam consisted of assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait, to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator (or designee). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose of study intervention (Day 1) to telephone Follow Up (28-35 days after lase dose of study intervention) (approximately up to 20 weeks) | An adverse event (AE) was any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. 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. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE. |
| Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks) | Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion. |
| Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks) | Abnormality in change from BL in vital signs included: standing diastolic blood pressure (BP) increase and decrease from BL of \>=20mmHg, standing systolic BP increase and decrease from BL of \>=30mmHg, supine diastolic BP increase and decrease from BL of \>=20mmHg, supine systolic BP increase and decrease from BL of \>=30mmHg. |
| Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks) | ECG assessments inlcuded PR, QT, QTcF intervals and QRS complex. ECG abnormalities in change from BL included: PR interval BL \>200msec and max \>=25% increase from BL, or BL \<=200msec and max \>=50% increase from BL, QRS interval percent change from BL \>=50%, QTcF change from BL \>=30 and \<=60msec, or change from BL \>60msec. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of PF-07258669 | At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4 | Cmax is the maximum observed plasma concentration. |
| Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4 | AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. |
| Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4 | AUCinf is the area under the plasma concentration time profile from time 0 extrapolated to infinite time. |
| Time for Cmax (Tmax) of PF-07258669 | At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4 | Tmax is the time for Cmax. |
| Terminal Half-life (t1/2) of PF-07258669 | At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4 | t1/2 is the terminal half-life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants in Cohort 1 underwent 4 treatment periods receiving up to 3 doses of PF-07258669 and up to 1 dose of placebo at 0.1mg, 0.3mg, 1mg, and 3mg on Day 1 in Periods 1-4 respectively. There was a washout interval of at least 7 days after each period. At each dose level, participants were assigned in an approximately 3:1 manner to receive PF-07258669 and placebo. | 10 |
| Cohort 2 Participants in Cohort 2 underwent 4 treatment periods receiving up to 3 doses of PF-07258669 and up to 1 dose of placebo on Day 1 at 10mg, 30mg, 100mg, and 200mg in Periods 1-4 respectively. There was a washout interval of at least 7 days after each period. At each dose level, participants were assigned in an approximately 3:1 manner to receive PF-07258669 and placebo. | 11 |
| Cohort 3 Participants in Cohort 3 underwent 1 treatment period and received 300 mg PF-07258669 or placebo in a 3:1 manner on Day 1 in Period 1. | 8 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 39.5 Years | 42.0 Years | 32.5 Years | 40.0 Years |
| Age, Customized 18-44 Years | 6 Participants | 8 Participants | 5 Participants | 19 Participants |
| Age, Customized 45-60 Years | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 10 Participants | 7 Participants | 26 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 4 Participants | 20 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 18 | 0 / 5 | 0 / 5 | 1 / 6 | 2 / 6 | 1 / 6 | 2 / 5 | 3 / 6 | 1 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 18 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
ECG assessments inlcuded PR, QT, QTcF intervals and QRS complex. ECG abnormalities in change from BL included: PR interval BL \>200msec and max \>=25% increase from BL, or BL \<=200msec and max \>=50% increase from BL, QRS interval percent change from BL \>=50%, QTcF change from BL \>=30 and \<=60msec, or change from BL \>60msec.
Time frame: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Population: The analysis set included all participants randomly assigned to study intervention and who received a dose of study intervention. Participants with evaluable ECG data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pooled Placebo | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >=30 and <=60msec | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | PR interval %change >=25/50% (BL >200msec and >=25% increase or BL <=200msec and >=50% increase) | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QTcF change >60msec | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria | QRS interval %change >=50% | 0 Participants |
Primary
Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
Abnormality in change from BL in vital signs included: standing diastolic blood pressure (BP) increase and decrease from BL of \>=20mmHg, standing systolic BP increase and decrease from BL of \>=30mmHg, supine diastolic BP increase and decrease from BL of \>=20mmHg, supine systolic BP increase and decrease from BL of \>=30mmHg.
Time frame: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Population: The analysis set included all participants randomly assigned to study intervention and who received a dose of study intervention. Participants with evaluable vital signs data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 1 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 1 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 1 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 1 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 1 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| Pooled Placebo | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 1 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 1 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 1mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 3mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 1 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 10mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 1 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 30mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 1 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 100mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 1 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 1 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
| PF-07258669 200mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP increase >=30mmHg | 1 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine diastolic BP decrease >=20mmHg | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing diastolic BP increase >=20mmHg | 0 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Standing systolic BP decrease >=30mmHg | 1 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP decrease >=30mmHg | 1 Participants |
| PF-07258669 300mg | Number of Participants With Change From BL in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria | Supine systolic BP increase >=30mmHg | 0 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)
Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion.
Time frame: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Population: The analysis set included all participants randomly assigned to study intervention and who received a dose of study intervention. Participants with evaluable laboratory values were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pooled Placebo | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 14 Participants |
| PF-07258669 0.1mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 5 Participants |
| PF-07258669 0.3mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 3 Participants |
| PF-07258669 1mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 4 Participants |
| PF-07258669 3mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 4 Participants |
| PF-07258669 10mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 6 Participants |
| PF-07258669 30mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 5 Participants |
| PF-07258669 100mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 6 Participants |
| PF-07258669 200mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 6 Participants |
| PF-07258669 300mg | Number of Participants With Clinical Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality) | 3 Participants |
Primary
Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings
The neurological exam consisted of assessment of higher cortical function, the cranial nerves, motor function, deep tendon reflexes, sensory exam, and coordination and gait, to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator (or designee).
Time frame: From BL to onsite Follow Up visit (up to 9 days after last dose of study intervention) (approximately up to 17 weeks)
Population: The analysis set included all participants randomly assigned to study intervention and who received a dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pooled Placebo | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 1mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 3mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 10mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 30mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 100mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 200mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
| PF-07258669 300mg | Number of Participants With Clinically-significant Change From BL in Neurological Examination Findings | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. 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. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
Time frame: From first dose of study intervention (Day 1) to telephone Follow Up (28-35 days after lase dose of study intervention) (approximately up to 20 weeks)
Population: The safety analysis set included all participants randomly assigned to study intervention and who received a dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 6 Participants |
| Pooled Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
| PF-07258669 0.1mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 0 Participants |
| PF-07258669 0.1mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 0 Participants |
| PF-07258669 0.3mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
| PF-07258669 1mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 1 Participants |
| PF-07258669 1mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
| PF-07258669 3mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
| PF-07258669 3mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 2 Participants |
| PF-07258669 10mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
| PF-07258669 10mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 1 Participants |
| PF-07258669 30mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
| PF-07258669 30mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 2 Participants |
| PF-07258669 100mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 3 Participants |
| PF-07258669 100mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
| PF-07258669 200mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 1 Participants |
| PF-07258669 200mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 1 Participants |
| PF-07258669 300mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | All-causality TEAEs | 2 Participants |
| PF-07258669 300mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 0 Participants |
Secondary
Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669
AUCinf is the area under the plasma concentration time profile from time 0 extrapolated to infinite time.
Time frame: At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Population: The PK parameter analysis population was defined as all participants randomly assigned to study intervention and who received a dose of study intervention, and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 2.659 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 14 |
| PF-07258669 0.1mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 8.252 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-07258669 0.3mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 28.55 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-07258669 1mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 76.63 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| PF-07258669 3mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 183.0 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 15 |
| PF-07258669 10mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 586.9 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 11 |
| PF-07258669 30mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 2156 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 12 |
| PF-07258669 100mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 4033 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
| PF-07258669 200mg | Area Under the Plasma Concentration Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-07258669 | 6036 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669
AUClast is the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
Time frame: At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Population: The PK parameter analysis population was defined as all participants randomly assigned to study intervention and who received a dose of study intervention, and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 2.421 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 13 |
| PF-07258669 0.1mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 7.826 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| PF-07258669 0.3mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 27.83 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| PF-07258669 1mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 75.84 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-07258669 3mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 182.2 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 16 |
| PF-07258669 10mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 584.8 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 11 |
| PF-07258669 30mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 2148 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 12 |
| PF-07258669 100mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 4013 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
| PF-07258669 200mg | Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07258669 | 5764 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
Secondary
Maximum Observed Concentration (Cmax) of PF-07258669
Cmax is the maximum observed plasma concentration.
Time frame: At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Population: The PK parameter analysis population was defined as all participants randomly assigned to study intervention and who received a dose of study intervention, and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Maximum Observed Concentration (Cmax) of PF-07258669 | 0.8439 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| PF-07258669 0.1mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 3.053 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| PF-07258669 0.3mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 10.72 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| PF-07258669 1mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 26.48 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| PF-07258669 3mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 53.30 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| PF-07258669 10mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 188.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 3 |
| PF-07258669 30mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 573.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
| PF-07258669 100mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 1173 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| PF-07258669 200mg | Maximum Observed Concentration (Cmax) of PF-07258669 | 1604 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 64 |
Secondary
Terminal Half-life (t1/2) of PF-07258669
t1/2 is the terminal half-life.
Time frame: At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Population: The PK parameter analysis population was defined as all participants randomly assigned to study intervention and who received a dose of study intervention, and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Terminal Half-life (t1/2) of PF-07258669 | 2.508 hour | Standard Deviation 0.92446 |
| PF-07258669 0.1mg | Terminal Half-life (t1/2) of PF-07258669 | 3.828 hour | Standard Deviation 0.92253 |
| PF-07258669 0.3mg | Terminal Half-life (t1/2) of PF-07258669 | 4.572 hour | Standard Deviation 0.9336 |
| PF-07258669 1mg | Terminal Half-life (t1/2) of PF-07258669 | 5.013 hour | Standard Deviation 0.52812 |
| PF-07258669 3mg | Terminal Half-life (t1/2) of PF-07258669 | 5.558 hour | Standard Deviation 0.78987 |
| PF-07258669 10mg | Terminal Half-life (t1/2) of PF-07258669 | 6.698 hour | Standard Deviation 1.6508 |
| PF-07258669 30mg | Terminal Half-life (t1/2) of PF-07258669 | 6.415 hour | Standard Deviation 1.5912 |
| PF-07258669 100mg | Terminal Half-life (t1/2) of PF-07258669 | 6.880 hour | Standard Deviation 1.9697 |
| PF-07258669 200mg | Terminal Half-life (t1/2) of PF-07258669 | 12.99 hour | Standard Deviation 10.045 |
Secondary
Time for Cmax (Tmax) of PF-07258669
Tmax is the time for Cmax.
Time frame: At 0 (prior to dose), 0.17, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours post dose on Day 1 in Periods 1 to 4
Population: The PK parameter analysis population was defined as all participants randomly assigned to study intervention and who received a dose of study intervention, and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled Placebo | Time for Cmax (Tmax) of PF-07258669 | 1.00 hour |
| PF-07258669 0.1mg | Time for Cmax (Tmax) of PF-07258669 | 1.00 hour |
| PF-07258669 0.3mg | Time for Cmax (Tmax) of PF-07258669 | 0.750 hour |
| PF-07258669 1mg | Time for Cmax (Tmax) of PF-07258669 | 0.750 hour |
| PF-07258669 3mg | Time for Cmax (Tmax) of PF-07258669 | 1.00 hour |
| PF-07258669 10mg | Time for Cmax (Tmax) of PF-07258669 | 1.00 hour |
| PF-07258669 30mg | Time for Cmax (Tmax) of PF-07258669 | 1.00 hour |
| PF-07258669 100mg | Time for Cmax (Tmax) of PF-07258669 | 1.25 hour |
| PF-07258669 200mg | Time for Cmax (Tmax) of PF-07258669 | 1.00 hour |