A Pharmacokinetic (PK) Study Of PF-00299804 And Dextromethorphan In Healthy Volunteers

An Open Label Phase 1, Randomized Cross Over Trial To Estimate The Effect Of PF- 00299804 On The Pharmacokinetics Of Dextromethorphan In Healthy Volunteers

A study to study the potential effect of PF-00299804 inhibition of CYP2D6 on dextromethorphan.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: reference [dextromethorphan]; Drug: test [PF-00299804 + dextromethorphan]

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and/or female of non childbearing potential 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).
• Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).
• Subjects must be CYP2D6 extensive metabolizers, ultrarapid metabolizers or intermediate metabolizers, as predicted by CYP2D6 genotyping.

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Any condition possibly affecting drug absorption (eg, gastrectomy).
• A positive urine drug screen.
• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for men (1 drink =5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
• Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half lives preceding the first dose of study medication.
• 12 lead ECG demonstrating QTc >450 msec at Screening. If QTc exceeds 450 msec, the ECG should be repeated two more times and the average of the three QTc values should be used to determine the subject's eligibility.
• Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study medication. Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication. Depo Provera® must be discontinued at least 6 months prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of <1 g/day. Limited use of non prescription medications that are not believed to affect subject safety or the overall results the study may be permitted on a case by case basis.
• Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
• History of sensitivity to heparin or heparin induced thrombocytopenia.
• Unwilling or unable to comply with the Lifestyle guidelines described in this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: A; Single 30 mg dose of dextromethorphan	Drug: reference [dextromethorphan]; single 30 mg oral dose
Experimental: B; Single 45 mg dose of PF-00299804 plus a single 30 mg oral dose of dextromethorphan	Drug: test [PF-00299804 + dextromethorphan]; single 45 mg oral dose of PF-00299804 and a single 30 mg oral dose of dextromethorphan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma AUCinf, AUClast and Cmax of dextromethorphan and dextrorphan when given alone and when given in combination with PF- 00299804.	7 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Tmax, t1/2, for dextromethorphan and dextrorphan and CL/F, and V/F for dextromethorphan (as data permit).	7 weeks
Plasma AUCinf, AUClast, Cmax, Tmax, t1/2, CL/F, and V/F (as data permit) of PF 00299804 when given alone.	7 weeks
Safety laboratory tests, physical examination, concomitant medication and adverse event monitoring.	7 weeks

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 8, 2009
• First Submitted That Met QC Criteria: October 21, 2009
• First Posted (Estimate): October 22, 2009

Study Record Updates

• Last Update Posted (Estimate): January 7, 2010
• Last Update Submitted That Met QC Criteria: January 5, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Drug-Drug interaction Study CYP2D6 inhibition Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Respiratory System Agents; Antitussive Agents; Dextromethorphan
• Other Study ID Numbers: A7471039