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

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Participants with laboratory abnormalities with ≥2 occurrences (without regard to baseline abnormality) that met pre-specified criteria were High-density lipoprotein (HDL) Cholesterol <0.8✕ lower limit of normal (LLN); Bicarbonate <0.9✕LLN; Calcitonin>1.0✕upper limit of normal (ULN); Triglycerides >1.3✕ULN; Aspartate Aminotransferase >3.0✕ULN; Low-density lipoprotein (LDL) Cholesterol >1.2✕ULN; Urine Glucose ≥1; Urine Ketones ≥1; Urine Leukocyte Esterase ≥1; Urine Leukocytes ≥20; Urine Hyaline Casts >1; Urine Hemoglobin ≥1; and Urine Nitrite ≥1.

Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in vital signs, were supine systolic blood pressure < 90 millimeters of mercury (mmHg), supine systolic blood pressure increase/decrease from baseline ≥ 30mmHg; supine diastolic blood pressure <50 mmHg, supine diastolic blood pressure increase/decrease from baseline ≥ 20mmHg; pulse rate <40 beats per minute (bpm) or >120 bpm.

The pre-specified categorical analysis criteria in ECG, were PR interval: value ≥ 300 milliseconds (msec), percentage change ≥ 25/50%; QRS duration: value ≥140 msec, percentage change ≥ 50%; QTcF interval: 450 < value ≤ 480 msec, 480 < value ≤ 500 msec, value >500 msec, and 30<change ≤ 60 msec, change >60 msec.

AUC24 is defined as area under the concentration-time profile from time 0 to 24 hours using Linear/Log trapezoidal method.

Cmax is defined as maximum plasma concentration observed directly from data.

Tmax is defined as time for Cmax observed directly from data as time of first occurrence.

t1/2 is defined as the time measured for the plasma concentration to decrease by one half.

Ae24 is defined as cumulative amount of drug recovered unchanged in urine over 24 hours using the method of urine concentration * volume of urine.

Ae24% is defined as percent of dose recovered unchanged in urine over the 24 hours using the method of 100 * Ae24/Dose

Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine over the dosing interval tau (Aetau) divided by area under the concentration time-curve from time 0 to time tau (AUCtau)