Study of Multiple Oral Doses of PF-07081532 in Adult Participants With Type 2 Diabetes Mellitus

Following laboratory parameters analyzed for laboratory examination: hemoglobin (HGB); hematocrit; erythrocytes; erythrocytes (Ery.) mean corpuscular volume; Ery. mean corpuscular HGB; Ery. mean corpuscular HGB concentration; platelets; leukocytes; lymphocytes; neutrophils; basophils; eosinophils; monocytes; bilirubin; direct bilirubin; indirect bilirubin; aspartate aminotransferase; alanine aminotransferase; gamma glutamyl transferase; alkaline phosphatase; albumin; urea nitrogen; creatinine; urate; cholesterol; high density lipoprotein (HDL) cholesterol; sodium; potassium; chloride; calcium; bicarbonate; thyroxine; free; thyrotropin; creatine kinase; amylase; triacylglycerol lipase; triglycerides; pH; urine glucose; ketones; urine protein; urine hemoglobin; urobilinogen; urine bilirubin; nitrite; leukocyte esterase; urine erythrocytes; urine leukocytes; epithelial cells; casts; and bacteria.

Time frame: Baseline up to 7-14 days after last dose of study drug (maximum: 56 days)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention and had at least 1 observation of the given laboratory test while on study treatment or during follow up. Here, number analyzed signifies number of participants evaluable for each category.

Triplicate 12-lead ECGs were collected using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. Pre-specified categorical criteria included: PR interval greater or equal to 300 msec, PR interval %Chg\>=25/50% (%Chg\>=25/50% denotes baseline \>200 msec and \>=25% increase or baseline less than or equal to \[\<=\] 200 msec and \>=50% increase), QRS interval \>=140 msec, QRS interval increase from baseline \>=50%, QT interval corrected using Fridericia's formula (QTcF) \>450 msec and \<=480 msec, QTcF \>480 msec and \<=500 msec, QTcF \>500 msec, QTcF increase from baseline \>30 msec and \<=60 msec, and QTcF increase from baseline \>60 msec.

Time frame: Baseline up to 14 days after last dose of study intervention (maximum: 56 days)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Pre-specified categorical criteria included: supine systolic blood pressure (SBP) less than (\<) 90 millimeters of mercury (mmHg), supine SBP increase from baseline greater or equal to (\>=) 30 mmHg, supine SBP decrease from baseline \>=30 mmHg, supine diastolic blood pressure (DBP) \<50 mmHg, supine DBP increase from baseline \>=20 mmHg, supine DBP decrease from baseline \>=20 mmHg, supine pulse rate \<40 beats per minutes (bpm), and supine pulse rate greater than (\>) 120 bpm. Supine BP was measured with the participant's arm supported at the level of the heart, and recorded to the nearest mmHg after approximately 5 minutes of rest.

Time frame: Baseline up to 14 days after last dose of study intervention (maximum: 56 days)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

An adverse event (AE) was any untoward medical occurrence in clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs.

Time frame: Baseline up to at least 28 days after last dose of study intervention (77 days)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

A treatment related adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study drug, considered related to the study drug (assessed by the investigator \[Yes/No\]). A serious AE (SAE) was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. A severe AE was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self-care activities of daily living. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period (starting after or on the first dose but before the last dose plus at least 28 days). AEs included all SAEs and non-SAEs.

Time frame: Baseline up to at least 28 days after last dose of study intervention (77 days)

Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

AUC24 of PF-07081532 were determined by Linear/Log trapezoidal method on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42

Population: All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics. Data collection was not planned for the placebo arms (Placebo \[T2DM\] and Placebo \[obesity\]).

Cmax of PF-07081532 were observed directly from data from time 0 to 24 hours on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42

Population: All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics. Data collection was not planned for the placebo arms (Placebo \[T2DM\] and Placebo \[obesity\]).

t1/2 of PF-07081532 was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 42

Population: All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics for t1/2. Data collection was not planned for the placebo arms (Placebo \[T2DM\] and Placebo \[obesity\]).

Tmax of PF-07081532 were observed directly from data as time of first occurrence on Study Day 1 and Study Day 42. On Study Day 1, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 20 mg, 40 mg, and 20 mg, respectively. On Study Day 42, participants in Arms of PF-07081532 20-60 mg (T2DM), PF-07081532 40-80 mg (T2DM), and PF-07081532 20-60 mg (obesity) received 60 mg, 80 mg, and 60 mg, respectively.

Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post dose on Study Day 1 and Study Day 42

Population: All randomized participants that received at least 1 dose of PF-07081532, have at least 1 of the PK parameters of interest calculated and contributed to the summary statistics. Data collection was not planned for the placebo arms (Placebo \[T2DM\] and Placebo \[obesity\]).