Clinical trial NCT00931073: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Huntington's Disease
Keywords: Drug Interactions
pharmacokinetics
CYP2D6
CYP2C19
ketoconazole
omeprazole
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Medivation, Inc.
First posted: 2009-07-02
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER

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.


Eligibility 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.

Primary outcomes:
measure: 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))
timeFrame: Period 1 Day 1
measure: 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))
timeFrame: Period 2 Day 4
measure: 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))
timeFrame: Period 3 Day 5
Secondary outcomes:
measure: Dimebon alone: Safety and tolerability (AE's, ECG, vital signs, safety labs)
timeFrame: Period 1 Day 1-7
measure: Dimebon + keto: Safety and tolerability (AE's, ECG, vital signs, safety labs)
timeFrame: Period 2 Day 1-12
measure: Dimebon + omeprazole: Safety and tolerability (AE's, ECG, vital signs, safety labs)
timeFrame: Period 3 Day 1-13
Other outcomes:
Locations:
city: Kalamazoo
country: United States
facility: Pfizer Investigational Site
state: Michigan
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: