Alzheimer's Disease, Huntington's Disease
Conditions
Keywords
Drug Interactions, pharmacokinetics, CYP2D6, CYP2C19, ketoconazole, omeprazole
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.
Interventions
DRUGDimebon 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
DRUGDimebon + 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
DRUGDimebon + 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
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Dimebon + omeprazole: Safety and tolerability (AE's, ECG, vital signs, safety labs) | Period 3 Day 1-13 |
| 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 |
Countries
United States
Outcome results
None listed