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

This study has been completed.
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00931073
First received: July 1, 2009
Last updated: November 17, 2009
Last verified: November 2009
  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 1

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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Chorea
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Dyskinesias
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mental Disorders
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Ketoconazole
Omeprazole
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Anti-Ulcer Agents
Antifungal Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Proton Pump Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014