A Drug-Drug Interaction Study to Examine the Impact of Itraconazole and Cyclosporine on PF-07081532 Pharmacokinetics in Overweight or Obese Adults

AUCinf is area under the plasma concentration-time profile from time zero extrapolated to infinite time. AUCinf is caluculated by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.

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. A 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. Any AEs occurring following start of treatment were considered as treatment emergent adverse event (TEAE). Events that occur during follow-up within the lag time of up to 35 days after the last dose of study intervention were counted as treatment emergent and attributed to the last treatment taken.

Participants with laboratory abnormalities (without regard to baseline abnormality) that met pre-specified criteria: For HEMATOLOGY, 1) Erythrocyte (Ery.) Mean Corpuscular Volume (fL) < 0.9*Lower limit of normal (LLN), 2) Ery. Mean Corpuscular Hemoglobin (picograms [pg]/cell) < 0.9*LLN; 3） Eosinophils/Leukocytes (%)> 1.2*upper limit of normal (ULN); for CLINICAL CHEMISTRY, Urate (mg/dL)> 1.2*ULN; for URINALYSIS, Urine Hemoglobin (Scalar)≥ 1.

Pre-specified criteria of vital signs included: Supine diastolic blood pressure (BP) <50mmHg, change from baseline maximum (max) decrease or increase >=20mmHg; supine pulse rate min< 40 beats per minute (bpm), max> 120 bpm; Supine systolic BP: Value <90 mmHg, change from baseline max decrease or increase >=30mmHg

Observed value at baseline and change from baseline in body weight at Day 5 of Period 1 , Day 5 of Period 2, and Day 10 of Period 3 were summarized.

The pre-specified criteria of ECG included: QT interval, aggregated: value >500 millisecond (msec); corrected QT Fridericia method (QTCF) interval, aggregated: 450<=value<480 msec, 480<=value<500 msec, value>=500 msec, 30<=changes<60msec, and changes>=60msec.

The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. Participants who respond "yes" to any question related to suicidal ideation or behavioral are reported in this outcome measure.

PHQ9-9 is a 9 item self-report scale for the assessment of depressive symptoms. A PHQ-9 score of ≥15 indicates clinically significant depression and was reported in this outcome measure. The total score ranges from 0 to 27 with the following interpretation: Score 1-4: minimal depression; Score 5-9: Mild depression; Score 10-14: moderate depression; Score 15-19 moderately severe depression; Score 20-27: Severe depression

Cmax is the maximum observed concentration and is observed directly from data.

Tmax is the Time to Cmax and is observed directly from data as time of first occurrence.

CL/F is the apparent oral clearance and is calculated by Dose/AUCinf.

Vz/F is the apparent volume of distribution and is calculated by Dose/ (AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve

T1/2 is calculated 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.