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

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00931073

Collaborator

Medivation, Inc. (Industry)

Enrollment

Location

Arms

Duration (Months)

7.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Alzheimer's Disease Huntington's Disease	Drug: Dimebon alone Drug: Dimebon + Ketoconazole Drug: Dimebon + Omeprazole	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (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

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Oct 1, 2009

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

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

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

Outcome Measures

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)) [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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.