A Study to Estimate the Effect of CYP3A4 Inhibitors (Itraconazole, Diltiazem or Verapamil) on the Pharmacokinetics of Single Dose PF- 00489791 in Healthy Volunteers

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: SR verapamil; Drug: itraconazole; Drug: PF-00489791; Drug: diltiazem

Study type: Interventional

Funder types: Industry

Identifiers

NCT02319148

2014-001979-31 (EudraCT Number)

A7331022

Details and patient eligibility

About

The primary objective of the study is to estimate the effects of different strong enzyme (CYP3A4) inhibitors, itraconazole, diltiazem, or verapamil on the single dose pharmacokinetics of PF-00489791 in healthy volunteers. The study will enroll approximately 18 subjects that are randomized to 1 of 3 treatment groups. The study is also intended to determine the safety and tolerability of single-dose PF- 00489791 when it is administered with steady-state itraconazole, diltiazem, or verapamil.

Enrollment: 22 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests) with a Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs.) and with a personally signed and dated informed consent document and who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Participating female subjects of non-childbearing potential must meet at least one of the following criteria: achieved postmenopausal status; have undergone a documented hysterectomy and/or bilateral oophorectomy; have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.

Exclusion criteria

• Subjects cannot be included in the study if there is: the presence/ history of any disorder that prevents study completion
• Evidence/history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
• Any surgical or medical condition that may interfere with the absorption distribution, metabolism, or excretion of the study drug
• A positive urine drug screen or history of regular excessive alcohol consumption or use of tobacco-or nicotine-containing products in excess or from 24-hours prior to admission until discharge
• Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 halflives preceding the first dose of study med.
• Out of range blood pressure including current evidence of orthostatic change in blood pressure
• Abnormal ECG or history or current evidence of clinically important cardiac conduction abnormalities.
• Also excluded are: pregnant or breastfeeding female subjects; male subjects with partners currently pregnant; male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as described in the protocol for the duration of the study and for at least 28 days after the last dose of investigational product.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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22 participants in 3 patient groups

Treatment B

Experimental group

Description:

Treatment B subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of itraconazole (200 mg once daily).

Treatment:

Drug: itraconazole

Drug: PF-00489791

Treatment C

Experimental group

Description:

Treatment C subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of diltiazem (240 mg once daily).

Treatment:

Drug: diltiazem

Drug: PF-00489791

Treatment D

Experimental group

Description:

Treatment D subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of verapamil (240 mg once daily).

Treatment:

Drug: SR verapamil

Drug: PF-00489791