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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00931073
• Other study ID #: B1451017
• Status: Completed
• Phase: Phase 1
• First received: July 1, 2009
• Last updated: November 17, 2009
• Start date: July 2009
• Est. completion date: October 2009

Study information

• Verified date: November 2009
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Huntington Disease
• Huntington's Disease

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Kalamazoo	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Medivation, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Dimebon alone: Safety and tolerability (AE's, ECG, vital signs, safety labs)		Period 1 Day 1-7	Yes
Secondary	Dimebon + keto: Safety and tolerability (AE's, ECG, vital signs, safety labs)		Period 2 Day 1-12	Yes
Secondary	Dimebon + omeprazole: Safety and tolerability (AE's, ECG, vital signs, safety labs)		Period 3 Day 1-13	Yes

External Links

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