Effect of Diltiazem Administration on CP-945,598 Pharmacokinetics

A Phase 1, Randomized, Fixed Sequence Study To Evaluate The Effect Of Multiple Dose Administration Of Modified Release Diltiazem On The Multiple Dose Pharmacokinetics Of CP-945,598 In Healthy Overweight And Obese Subjects

A recently completed clinical drug interaction study of CP-945,598 with ketoconazole, a potent CYP3A inhibitor, showed that coadministration of CP-945,598 with ketoconazole results in an approximately 5-fold increase in CP-945,598 total exposure (AUC) and 4-fold increase in Cmax. Therefore, the sensitivity of CP-945,598 pharmacokinetics (PK) to less potent CYP3A inhibitors needs to be characterized to support labeling and registration.

Diltiazem is a known substrate and moderate mechanism-based inhibitor of the CYP3A enzyme system and was chosen as the moderate CYP3A inhibitor for this study as it is a clinically relevant medication likely to be prescribed concomitantly with CP-945,598 given the increased risk of hypertension and cardiovascular disease in the obese patient population.

Inclusion Criteria:

• No clinically relevant abnormalities based upon medical history, physical exam, 12-lead ECG, and clinical lab tests
• Body Mass Index (BMI) ~ 27-40 kg/m2, inclusive
• Personally signed inform consent document

Exclusion Criteria:

• Evidence or history of significant acute or chronic disease
• Pregnant or nursing females
• Screening PR interval > 220 msec
• Sitting blood pressure <= 90 mmHg systolic or <= 60 mmHg diastolic