This study has four parts: Part A, Part B, Part C, and Part D. The purpose of Part A of this study is to learn about the: * safety, * tolerability, * how PF-07293893 is processed by the body when multiple doses of PF-07293893 are given to healthy participants. The purpose of Part B of this study is to understand the effect of multiple doses of PF-07393893 on the amount of midazolam when given as a single dose by mouth. The purpose of part C of this study is to understand how PF-07293893 is changed in the body and how much PF-07293893 and it's changed forms are being removed in urine and feces after a single dose given to single participants. The purpose of Part D is to understand the effect of multiple doses of PF-07293893 on the amount of glycogen (storage form of glucose) in the muscle of healthy participants. Part B, C and D will be done if the results of Part A support further study of PF-07293893. The study is seeking participants who: * are females who are not able to give birth to a child. These female participants should be between 18 to 65 years of age. * are males of 18 to 65 years of age. * have a body mass index (BMI) of 20.0 to 35.0 kilograms per squared meter. * have total body weight of more than 45 kilograms (99 pounds). For a given participant in Part A, the total study is going to last up to about 11 weeks. This includes from the time of selection till the last follow-up phone call. The participants will be selected if they are fit for the study 28 days before the first dose of the study medicines. Participants who are selected will be admitted to the study site on Day 1 for around 18 days. Following discharge, participants will return for an on-site follow-up visit 7 to 10 days after receiving the final dose of the study medicine. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given. For a given participant in Part B, the total study is going to last up to about 11 weeks. This study consists of 4 periods. Participants will be admitted to the study site on Day 1 and discharged on Day 3 in period 4. Following discharge, participants will return for an on-site follow-up visit 7 to 10 days after receiving the final dose of the study medicine in period 4. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given in period 4. For a given participant in Part C, the total study is going to last up to about 9 weeks. Participants will be admitted to the study site on Day 1. The participants will be discharged on Day 11 after giving the study medicine. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given. For a given participant in Part D, the total study is going to last up to about 11 weeks. The participants will be selected if they are fit for the study 28 days before the first dose of the study medicines. Participants who are selected will be admitted to the study site on Day -3 for around 17 days. Following discharge, participants will return for an on-site follow-up visit 7 to 10 days after receiving the final dose of the study medicine. The follow-up contact may be via a telephone call and will happen 28 to 35 days after the final dose of study medicine is given.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
88
PF-07293893 will be administered as tablets every day (QD) over 14 days
Placebo will be administered as tablets; QD over 14 days
Single doses of Midazolam will be administered as oral solution alone and in combination with PF-07293893
Pfizer Clinical Research Unit - New Haven
New Haven, Connecticut, United States
Yale University/Magnetic Resonance Research Center (MRRC)
New Haven, Connecticut, United States
Pfizer Clinical Research Unit - Brussels
Brussels, Bruxelles-capitale, Région de, Belgium
Part A:Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Time frame: Baseline up to 35 days after last dose of study intervention (approximately 11 weeks).
Part A: Number of Participants With Clinical Laboratory Abnormalities
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks).
Part A: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks).
Part A: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks).
Part A: Number of Participants With Clinically-Significant Change From Baseline in Physical Examination Findings
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks).
Part A: Number of Participants With Clinically-Significant Change From Baseline in Neurological Examination Findings
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks).
Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose on Period 1/Day 1
Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post dose on Period 2/Day 2
Part B: Maximum Observed Plasma Concentration (Cmax) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post dose on Period 4/Day 1
Part B: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose on Period 1/Day 1
Part B: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post dose on Period 2/Day 2
Part B: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post dose on Period 4/Day 1
Part B: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose on Period 1/Day 1
Part B: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post dose on Period 2/Day 2
Part B: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of Midazolam
Time frame: Time Frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post dose on Period 4/Day 1
Part C: Total recovery of drug-related material in urine and feces separately, and both routes combined, expressed as a percent of total dose administered.
Time frame: Predose to Day 11
Part D: Change from baseline in glycogen on Day 14 as measured by 13C MRS of skeletal muscle
Time frame: Day 14 (last day of dosing)
Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose on Day 1
Part A: Maximum Observed Plasma Concentration (Cmax) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose on Day 14
Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (tau) (AUCtau) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose on Day 1
Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to Dosing Interval (tau) (AUCtau) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose on Day 14
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose on Day 1
Part A: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose on Day 14
Part A: Amount of PF-07293893 Excreted Unchanged in Urine Over the Dosing Interval Tau (Aetau)
Time frame: On Day 14, urine collection for PK to occur over 0-tau, according to dosing frequency (ie, 0-12 hours for 12 hour dosing interval; 0-24 hours for 24 hour dosing interval)
Part A: Percentage of Dose of PF-07293893 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)
Time frame: On Day 14, urine collection for PK to occur over 0-tau, according to dosing frequency (ie, 0-12 hours for 12 hour dosing interval; 0-24 hours for 24 hour dosing interval)
Part A: Renal Clearance of PF-07293893
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Time frame: On Day 14, urine collection for PK to occur over 0-tau, according to dosing frequency (ie, 0-12 hours for 12 hour dosing interval; 0-24 hours for QD dosing interval)
Part B: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Time frame: Baseline up to 35 days after last dose of study intervention (approximately 10 weeks)
Part B: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks)
Part B: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks)
Part B: Number of Participants With Clinical Laboratory Abnormalities
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 7 weeks)
Part B: Number of Participants With Clinically-Significant Change From Baseline in Physical Examination Findings
Time frame: Baseline up to 35 days after last dose of study intervention (approximately 10 weeks)
Part C: Maximum Observed Plasma Concentration (Cmax) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose
Part C: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose
Part C: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose
Part C: Area under the plasma concentration-time curve from time 0 to Extrapolated Infinite Time (AUCinf) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose
Part C: Terminal half life (t1/2) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose
Part C: Apparent clearance (CL/F) of PF-07293893 from plasma
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose
Part C: Apparent volume of distribution (Vz/F) of PF-07293893
Time frame: predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72 hours post dose
Part D: Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Time frame: Baseline up to 35 days after last dose of study intervention (approximately 11 weeks)
Part D: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 8 weeks)
Part D: Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 8 weeks)
Part D: Number of Participants With Clinical Laboratory Abnormalities
Time frame: Baseline up to 10 days after last dose of study intervention (approximately 8 weeks)