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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease; Huntington's Disease
• Intervention / Treatment: Drug: Dimebon alone; Drug: Dimebon + Ketoconazole; Drug: Dimebon + Omeprazole

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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))	Period 1 Day 1
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))	Period 2 Day 4
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))	Period 3 Day 5

Secondary Outcome Measures

Outcome Measure	Time Frame
Dimebon alone: Safety and tolerability (AE's, ECG, vital signs, safety labs)	Period 1 Day 1-7
Dimebon + keto: Safety and tolerability (AE's, ECG, vital signs, safety labs)	Period 2 Day 1-12
Dimebon + omeprazole: Safety and tolerability (AE's, ECG, vital signs, safety labs)	Period 3 Day 1-13

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Medivation, Inc.

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: July 1, 2009
• First Submitted That Met QC Criteria: July 1, 2009
• First Posted (Estimate): July 2, 2009

Study Record Updates

• Last Update Posted (Estimate): November 18, 2009
• Last Update Submitted That Met QC Criteria: November 17, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: pharmacokinetics; Drug Interactions; omeprazole; CYP2D6; CYP2C19; ketoconazole
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Tauopathies; Cognition Disorders; Chorea; Alzheimer Disease; Huntington Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole; Omeprazole
• Other Study ID Numbers: B1451017