Healthy Participants
Conditions
Keywords
PF-07293893, Single ascending dose, Safety, Tolerability, Pharmacokinetics
Brief summary
The purposes of the study are: To learn about the safety and tolerability of study medicine (PF-07293893). Tolerability is the extent to which side effects can be tolerated. Side effects are unwanted reactions to the study medicine. To measure the amount of PF-07293893 in blood after the medicine is taken by mouth. The study is seeking participants who: * Are females of non-childbearing potential and males 18 to 65 years of age * Are in generally healthy condition * Have not had viral infections (HIV, HBV or HCV). HIV, human immunodeficiency virus. HBV, human hepatitis B virus. HCV, human hepatitis C virus. Participants will receive either PF-07293893 or placebo (dummy pill) by chance. Participants will undergo up to 4 treatments periods in this study. Everyone will receive up to 4 doses of study medicine and up to 2 doses of placebo. In each period, participants will stay in study clinic for 5 days. There will be at least 2 days between each treatment period. Participants will be involved in this study for about 14 weeks. During their stay, participants will undergo several examinations. Participants will also have their blood collected by the study doctors for several times.
Interventions
DRUGPF-07293893
PF-07293893 will be prepared as an oral suspension given in escalating single doses to be determined.
DRUGPlacebo
Matching placebo will be prepared as an oral suspension given in each cohort.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
This study is seeking participants who are: * Females of non-childbearing potential and males 18 to 65 years of age, inclusive, at the time of signing the informed consent document (ICD) who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. This study is not seeking participants who have: * 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). * History of human immunodeficiency virus infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen, or hepatitis C antibody. Hepatitis B vaccination is allowed. * Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to coronavirus disease 2019 (COVID-19) pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. * Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants \<60 years; and ≥150/90 mm/Hg for participants ≥60 years old, following at least 5 minutes of supine rest. * Renal impairment as defined by an estimated glomerular filtration rate (eGFR) \<75 mL/min/1.73m². * Standard 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results * Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin ≥1.05 × upper limit of normal (ULN), participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Day 1 of first dose up to maximum of 35 days post last dose (up to 60 days) | An Adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events with onset dates on or after the start of the study drug. |
| Number of Participants With Laboratory Test Abnormalities | Day 1 of first dose up to maximum of 9 days post last dose (up to 34 days) | Following parameters were analyzed for laboratory abnormalities: hematology (lymphocytes \<0.8\*lower limit of normal \[LLN\], lymphocytes/leukocytes \<0.8\*LLN, neutrophils \<0.8\*LLN, neutrophils/leukocytes \<0.8\*LLN, eosinophils/leukocytes \>1.2\*upper limit of normal \[ULN\], monocytes \>1.2\*ULN, monocytes/leukocytes \>1.2\*ULN); clinical chemistry (aspartate aminotransferase \>3.0\*ULN, potassium \>1.1\*ULN, creatine kinase \>2.0\*ULN); urinalysis (urine specific gravity \<1.003 ,\>1.030, ketones \>=1, urine hemoglobin \>=1, urobilinogen \>=1, urine bilirubin \>=1, leukocyte esterase \>=1). In this outcome measure, participants with any laboratory abnormalities are reported. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Day 1 of first dose up to maximum of 9 days post last dose (up to 34 days) | Vital signs assessments included blood pressure, pulse rate, respiratory rate and body temperature. Clinical significance of vital signs was determined based by investigator's discretion. |
| Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | Day 1 of first dose up to maximum of 9 days post last dose (up to 34 days) | ECG parameters included heart rate, PR interval, QTc corrected using Fridericia's formula (QTcF) and QRS complex. Clinically significant ECG findings were determined by the investigator's discretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of PF-07293893 | Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period | — |
| Terminal Half-Life (t1/2) of PF-07293893 | Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period | t1/2 was calculated as log\^e (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. |
| Time for Cmax (Tmax) of PF-07293893 | Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period | — |
| Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period | AUClast was calculated using linear/log trapezoidal method. |
| Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period | AUCinf was calculated as AUClast + (Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. |
Countries
Belgium
Participant flow
Pre-assignment details
A total of 30 participants (initially randomized participants and replacement participants) were enrolled in this study. All participants received at least 1 dose of study intervention and were assigned in the study into 3 cohorts. As planned, there were replacement participants in the study who were not initially randomized, but they replaced those participants who discontinued in any treatment period due to reasons other than safety; this was per investigator's and sponsor's discretion.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 In this cohort participants were randomized to received placebo matched to PF-07293893 or PF-07293893 (10 mg, 30 mg, 100 mg or 300 mg) in sequence 1 or 2 or 3 or 4. | 10 |
| Cohort 2 In this cohort participants were randomized to received placebo matched to PF-07293893 or PF-07293893 (300mg \[fast/fed\],750 mg, 1500 mg) in sequence 1 or 2 or 3 or 4. | 11 |
| Cohort 3 In this cohort participants were randomized to received placebo matched to PF-07293893 or PF-07293893 (750 mg \[fast/fed\], 900 mg, 1200 mg) in sequence 1 or 2 or 3 or 4. | 9 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | No longer met eligibility criteria | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Period 2 | Personal reason | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Period 3 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Customized Age 18-44 Years | 6 Participants | 7 Participants | 4 Participants | 17 Participants |
| Age, Customized Age 45-64 Years | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Age, Customized Age >=65 Years | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 10 Participants | 8 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 9 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 2 | 0 / 18 | 0 / 2 |
| other Total, other adverse events | 1 / 6 | 2 / 6 | 1 / 6 | 2 / 6 | 3 / 5 | 3 / 6 | 3 / 6 | 5 / 6 | 8 / 12 | 2 / 6 | 4 / 6 | 3 / 6 | 4 / 6 | 2 / 2 | 1 / 2 | 6 / 18 | 1 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 2 | 0 / 18 | 0 / 2 |
Outcome results
Primary
Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings
ECG parameters included heart rate, PR interval, QTc corrected using Fridericia's formula (QTcF) and QRS complex. Clinically significant ECG findings were determined by the investigator's discretion.
Time frame: Day 1 of first dose up to maximum of 9 days post last dose (up to 34 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo: CRYS/Fasted Cohort 2 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo: CRYS/Fed Cohort 2 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo: SDD/Fasted Combined for All Cohorts | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo: SDD/Fed Cohort 2 | Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs assessments included blood pressure, pulse rate, respiratory rate and body temperature. Clinical significance of vital signs was determined based by investigator's discretion.
Time frame: Day 1 of first dose up to maximum of 9 days post last dose (up to 34 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo: CRYS/Fasted Cohort 2 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo: CRYS/Fed Cohort 2 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo: SDD/Fasted Combined for All Cohorts | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo: SDD/Fed Cohort 2 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities
Following parameters were analyzed for laboratory abnormalities: hematology (lymphocytes \<0.8\*lower limit of normal \[LLN\], lymphocytes/leukocytes \<0.8\*LLN, neutrophils \<0.8\*LLN, neutrophils/leukocytes \<0.8\*LLN, eosinophils/leukocytes \>1.2\*upper limit of normal \[ULN\], monocytes \>1.2\*ULN, monocytes/leukocytes \>1.2\*ULN); clinical chemistry (aspartate aminotransferase \>3.0\*ULN, potassium \>1.1\*ULN, creatine kinase \>2.0\*ULN); urinalysis (urine specific gravity \<1.003 ,\>1.030, ketones \>=1, urine hemoglobin \>=1, urobilinogen \>=1, urine bilirubin \>=1, leukocyte esterase \>=1). In this outcome measure, participants with any laboratory abnormalities are reported.
Time frame: Day 1 of first dose up to maximum of 9 days post last dose (up to 34 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| Placebo: CRYS/Fasted Cohort 2 | Number of Participants With Laboratory Test Abnormalities | 2 Participants |
| Placebo: CRYS/Fed Cohort 2 | Number of Participants With Laboratory Test Abnormalities | 1 Participants |
| Placebo: SDD/Fasted Combined for All Cohorts | Number of Participants With Laboratory Test Abnormalities | 7 Participants |
| Placebo: SDD/Fed Cohort 2 | Number of Participants With Laboratory Test Abnormalities | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An Adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were events with onset dates on or after the start of the study drug.
Time frame: Day 1 of first dose up to maximum of 35 days post last dose (up to 60 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Placebo: CRYS/Fasted Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| Placebo: CRYS/Fed Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| Placebo: SDD/Fasted Combined for All Cohorts | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Placebo: SDD/Fed Cohort 2 | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893
AUCinf was calculated as AUClast + (Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period
Population: PK Parameter Set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention and have at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 799.3 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 36 |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 2700 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 11 |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 8397 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 24 |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 2219 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 20 |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 9001 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 30 |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 30010 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 25 |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 50280 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 37 |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 89780 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 17 |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 67190 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 42 |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 81070 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 49 |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 101200 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 21 |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 103900 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 30 |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07293893 | 94570 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 34 |
Secondary
Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893
AUClast was calculated using linear/log trapezoidal method.
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period
Population: PK Parameter Set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention and have at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 782.5 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 37 |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 2671 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 11 |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 8354 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 24 |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 2057 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 19 |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 8910 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 30 |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 29900 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 25 |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 50150 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 37 |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 89220 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 17 |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 66890 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 42 |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 80700 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 48 |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 100700 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 20 |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 103400 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 30 |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-07293893 | 94210 nanogram*hour per milliliter (ng*hr/ mL) | Geometric Coefficient of Variation 34 |
Secondary
Maximum Plasma Concentration (Cmax) of PF-07293893
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period
Population: Pharmacokinetic (PK) parameter Set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 110.2 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 39 |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 360.1 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 19 |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 1173 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 24 |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 147.2 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 20 |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 690.6 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 23 |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 3613 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 34 |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 5632 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 28 |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 6831 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 9 |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 6203 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 22 |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 5653 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 33 |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 7894 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 15 |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 7458 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 18 |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Maximum Plasma Concentration (Cmax) of PF-07293893 | 7398 nanogram per milliliter (ng/ mL) | Geometric Coefficient of Variation 22 |
Secondary
Terminal Half-Life (t1/2) of PF-07293893
t1/2 was calculated as log\^e (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve.
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period
Population: PK Parameter Set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention and have at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Terminal Half-Life (t1/2) of PF-07293893 | 13.88 Hour | Standard Deviation 2.816 |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Terminal Half-Life (t1/2) of PF-07293893 | 15.32 Hour | Standard Deviation 1.4386 |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Terminal Half-Life (t1/2) of PF-07293893 | 13.92 Hour | Standard Deviation 2.0673 |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Terminal Half-Life (t1/2) of PF-07293893 | 21.50 Hour | Standard Deviation 6.5593 |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Terminal Half-Life (t1/2) of PF-07293893 | 13.70 Hour | Standard Deviation 1.2767 |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Terminal Half-Life (t1/2) of PF-07293893 | 11.34 Hour | Standard Deviation 2.1157 |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Terminal Half-Life (t1/2) of PF-07293893 | 10.07 Hour | Standard Deviation 3.0057 |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Terminal Half-Life (t1/2) of PF-07293893 | 11.00 Hour | Standard Deviation 1.3977 |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Terminal Half-Life (t1/2) of PF-07293893 | 10.54 Hour | Standard Deviation 2.2872 |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Terminal Half-Life (t1/2) of PF-07293893 | 10.90 Hour | Standard Deviation 1.2152 |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Terminal Half-Life (t1/2) of PF-07293893 | 10.76 Hour | Standard Deviation 1.3132 |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Terminal Half-Life (t1/2) of PF-07293893 | 10.44 Hour | Standard Deviation 2.1452 |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Terminal Half-Life (t1/2) of PF-07293893 | 9.578 Hour | Standard Deviation 1.1218 |
Secondary
Time for Cmax (Tmax) of PF-07293893
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24, 48 and 72 hours post dose of any treatment period
Population: PK parameter Set included all participants randomly assigned to study intervention and who received at least 1 dose of study intervention and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-07293893 10 mg: SDD/Fasted Cohort 1 | Time for Cmax (Tmax) of PF-07293893 | 1.00 Hour |
| PF-07293893 30 mg: SDD/Fasted Cohort 1 | Time for Cmax (Tmax) of PF-07293893 | 1.01 Hour |
| PF-07293893 100 mg: SDD/Fasted Cohort 1 | Time for Cmax (Tmax) of PF-07293893 | 2.03 Hour |
| PF-07293893 300 mg: CRYS/Fasted Cohort 2 | Time for Cmax (Tmax) of PF-07293893 | 2.50 Hour |
| PF-07293893 300 mg: CRYS/Fed Cohort 2 | Time for Cmax (Tmax) of PF-07293893 | 6.00 Hour |
| PF-07293893 300 mg: SDD/Fasted Cohort 1 | Time for Cmax (Tmax) of PF-07293893 | 2.51 Hour |
| PF-07293893 750 mg: SDD/Fasted Cohort 2 | Time for Cmax (Tmax) of PF-07293893 | 3.51 Hour |
| PF-07293893 750 mg: SDD/Fasted Cohort 3 | Time for Cmax (Tmax) of PF-07293893 | 2.50 Hour |
| PF-07293893 750 mg: SDD/Fasted Combined for Cohorts 2 and 3 | Time for Cmax (Tmax) of PF-07293893 | 3.01 Hour |
| PF-07293893 750 mg: SDD/Fed Cohort 3 | Time for Cmax (Tmax) of PF-07293893 | 5.00 Hour |
| PF-07293893 900 mg: SDD/Fasted Cohort 3 | Time for Cmax (Tmax) of PF-07293893 | 4.00 Hour |
| PF-07293893 1200 mg: SDD/Fasted Cohort 3 | Time for Cmax (Tmax) of PF-07293893 | 4.00 Hour |
| PF-07293893 1500 mg: SDD/Fasted Cohort 2 | Time for Cmax (Tmax) of PF-07293893 | 4.01 Hour |