A Study to Understand the Effect of Multiple Ascending Doses of PF-07293893 in Healthy Adult Participants

Inclusion criteria

• Females of non-childbearing potential and males 18 to 65 years of age (except for optional Part C in which only males will be recruited), inclusive, at the time of signing the ICD who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• BMI of 20-35 kg/m2; and a total body weight >45kg (99 lb).
• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Capable of giving signed informed consent.

Exclusion criteria

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, ophthalmologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).

History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. 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 that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Part C Only: History of irregular bowel movements including irritable bowel syndrome or frequent episodes of diarrhea or constipation defined by less than 1 bowel movement on average per 2 days or lactose intolerance.
• 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 with the exception of moderate/strong CYP3A inducers or inhibitors which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention.
• Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study.
• Previous exposure to PF-07293893 treatment.
• A positive urine drug test.
• Screening supine 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. If systolic BP is ≥ 140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
• Renal impairment as defined by an estimated glomerular filtration rate (eGFR) <75 mL/min/1.73m². Since participants are 18 years to 65 years, 2021 Screat-based CKD-EPI eGFR is the recommended formula.
• Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >450 ms, complete LBBB, signs of an acute or indeterminate- age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third- degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer interpreted- ECGs should be overread by a physician experienced in reading ECGs before excluding a participant.
• 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: ALT, AST, Bili ≥ 1.05 x 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.

CK > 2.5 x ULN.

• History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine).
• Use of tobacco or nicotine-containing products in excess of the equivalent of 5 cigarettes/day or 2 chews of tobacco/day.
• Part B Only: History of sensitivity reaction to midazolam, or any of the formulation components.
• Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
• Part D Only: Any contra-indication to Magnetic Resonance Imaging, including noncompatible metallic implants, severe claustrophobia, or the inability to remain still for the duration of the scan session.