A Phase I Study To Estimate The Effect Of Ketoconazole And Omeprazole On The Pharmacokinetics Of Dimebon In Healthy Subjects Who Are Normal Or Poor CYP2D6 Metabolizers - Full Text View

Sponsor:	Pfizer
Collaborator:	Medivation, Inc.
Information provided by:	Pfizer
ClinicalTrials.gov Identifier:	NCT00931073

Purpose

This study will evaluate the potential for a drug-drug interaction of Dimebon with ketoconazole and omeprazole, potent inhibitors of the drug metabolizing enzymes CYP3A4 and CYP2C19, respectively.

Condition	Intervention	Phase
Alzheimer's Disease Huntington's Disease	Drug: Dimebon alone Drug: Dimebon + Ketoconazole Drug: Dimebon + Omeprazole	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label
Official Title:	A Phase I, Open-Label, Three-Period, Fixed-Sequence Study To Estimate The Steady-State Effect Of Ketoconazole And Omeprazole On The Single-Dose Pharmacokinetics Of Dimebon [PF-01913539] In Healthy CYP2D6 EM And PM Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease chorea-acanthocytosis familial paroxysmal nonkinesigenic dyskinesia Huntington disease McLeod neuroacanthocytosis syndrome

MedlinePlus related topics: Alzheimer's Disease Drug Reactions Huntington's Disease

Drug Information available for: Ketoconazole Omeprazole Fungarest Omeprazole magnesium Esomeprazole Sodium Esomeprazole magnesium Dimebolin

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Dimebon alone: Dimebon PK in CYP2D6 EMs and PMs (Cmax, Tmax, AUCinf (as data permit), AUClast, and t1/2 (as data permit), CL/F (as data permit) and V/F (as data permit)) [ Time Frame: Period 1 Day 1 ] [ Designated as safety issue: No ]
Dimebon + keto: Dimebon PK in CYP2D6 EMs and PMs (Cmax, Tmax, AUCinf (as data permit), AUClast, and t1/2 (as data permit), CL/F (as data permit) and V/F (as data permit)) [ Time Frame: Period 2 Day 4 ] [ Designated as safety issue: No ]
Dimebon + omeprazole: Dimebon PK in CYP2D6 EMs and PMs (Cmax, Tmax, AUCinf (as data permit), AUClast, and t1/2 (as data permit), CL/F (as data permit) and V/F (as data permit)) [ Time Frame: Period 3 Day 5 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Dimebon alone: Safety and tolerability (AE's, ECG, vital signs, safety labs) [ Time Frame: Period 1 Day 1-7 ] [ Designated as safety issue: Yes ]
Dimebon + keto: Safety and tolerability (AE's, ECG, vital signs, safety labs) [ Time Frame: Period 2 Day 1-12 ] [ Designated as safety issue: Yes ]
Dimebon + omeprazole: Safety and tolerability (AE's, ECG, vital signs, safety labs) [ Time Frame: Period 3 Day 1-13 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	July 2009
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Period 1	Drug: Dimebon alone Pharmacokinetics of a single oral dose of 10 mg Dimebon (tablet) will be assessed in subjects with a CYP2D6 extensive and poor metabolizer status based on genotyping as screening
Experimental: Period 2	Drug: Dimebon + Ketoconazole Pharmacokinetics of a single oral dose of 10 mg Dimebon (tablet) will be assessed on Day 4 during the daily administration of ketoconazole (400 mg, Day 1-11) in subjects with a CYP2D6 extensive and poor metabolizer status based on genotyping as screening
Experimental: Period 3	Drug: Dimebon + Omeprazole Pharmacokinetics of a single oral dose of 10 mg Dimebon (tablet) will be assessed on Day 5 during the daily administration of omeprazole(40 mg, Day 1-12) in subjects with a CYP2D6 extensive and poor metabolizer status based on genotyping as screening

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Subjects must have either a CYP2D6 EM (n=12) or PM (n=12) status based on genotyping at screening.
Subjects must have a CYP2C19 EM status based on status at screening.

Exclusion Criteria:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
Subjects with any history of a previous seizure or convulsion or significant head trauma.
Subjects specifically allergic to imidazole antifungal agents.
Subjects specifically allergic to omeprazole or other proton pump inhibitors.
Any condition possibly affecting drug absorption (eg, gastrectomy).
Subjects with hypersensitivity reactions to Dimebon or other antihistamines.
Consumption of grapefruit or grapefruit containing products within 7 days prior to the first dose of study medication.
Subjects currently taking omeprazole, other proton pump inhibitors, antacids, H2-blockers or CYP2C19 inhibitors.
Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of nonhormonal contraception as outlined in this protocol from at least 14 days prior to the first dose of study medication.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00931073

Locations

United States, Michigan
Pfizer Investigational Site
Kalamazoo, Michigan, United States, 49007

Sponsors and Collaborators

Pfizer

Medivation, Inc.

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00931073 History of Changes
Other Study ID Numbers:	B1451017
Study First Received:	July 1, 2009
Last Updated:	November 17, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

Drug Interactions
pharmacokinetics
CYP2D6

CYP2C19
ketoconazole
omeprazole

Additional relevant MeSH terms:

Alzheimer Disease
Huntington Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Basal Ganglia Diseases
Chorea
Dyskinesias
Movement Disorders

Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Cognition Disorders
Ketoconazole
Omeprazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Anti-Ulcer Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 09, 2012