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

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Randomized, Open-label, 3-sequence, 4-treatment, Incomplete Block Design To Estimate The Effect Of Steady State Cyp3a4 Inhibitors (Itraconazole, Diltiazem Or Verapamil) On The Pharmacokinetics Of Singe Dose Pf-00489791 In Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02319148
• Other study ID #: A7331022
• Secondary ID: 2014-001979-31
• Status: Completed
• Phase: Phase 1
• First received: September 17, 2014
• Last updated: December 12, 2014
• Start date: July 2014
• Est. completion date: October 2014

Study information

• Verified date: December 2014
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• itraconazole
itraconazole dosed at 200 mg
• diltiazem
diltiazem dosed at 240 mg
• SR verapamil
SR verapamil dosed at 240 mg

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax)	peak or maximum observed concentration observed directly from data	0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, hours post-dose	No
Primary	Area under the Concentration-Time Curve (AUC)	AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.	0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, hours post-dose	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)	Observed directly from data as time of first occurrence	0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, hours post-dose	No
Secondary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, hours post-dose	No
Secondary	Apparent Oral Clearance (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, hours post-dose	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)	0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, hours post-dose	No
Secondary	Apparent Volume of Distribution (Vz/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.	0, 0.5, 1, 2, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, hours post-dose	No

External Links

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