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
This study has been completed.
Sponsor:
Pfizer
Collaborator:
Medivation, Inc.
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00931073
First received: July 1, 2009
Last updated: November 17, 2009
Last verified: November 2009
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Alzheimer's Disease Huntington's Disease |
Drug: Dimebon alone Drug: Dimebon + Ketoconazole Drug: Dimebon + Omeprazole |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: 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 |
Resource links provided by NLM:
Genetics Home Reference related topics:
Alzheimer disease
chorea-acanthocytosis
Huntington disease
McLeod neuroacanthocytosis syndrome
Drug Information available for:
Ketoconazole
Omeprazole
Omeprazole magnesium
Esomeprazole
Esomeprazole Sodium
Esomeprazole magnesium
U.S. FDA Resources
Further study details as provided by Pfizer:
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)) [ Time Frame: Period 1 Day 1 ] [ Designated as safety issue: No ]
- 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)) [ Time Frame: Period 2 Day 4 ] [ Designated as safety issue: No ]
- 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)) [ Time Frame: Period 3 Day 5 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Dimebon alone: Safety and tolerability (AE's, ECG, vital signs, safety labs) [ Time Frame: Period 1 Day 1-7 ] [ Designated as safety issue: Yes ]
- Dimebon + keto: Safety and tolerability (AE's, ECG, vital signs, safety labs) [ Time Frame: Period 2 Day 1-12 ] [ Designated as safety issue: Yes ]
- Dimebon + omeprazole: Safety and tolerability (AE's, ECG, vital signs, safety labs) [ Time Frame: Period 3 Day 1-13 ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 24 |
| Study Start Date: | July 2009 |
| Study Completion Date: | October 2009 |
| Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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
|
Eligibility| Ages Eligible for Study: | 18 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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.
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Director, Clinical Trial Disclosure Group, Pfizer, Inc. |
| ClinicalTrials.gov Identifier: | NCT00931073 History of Changes |
| Other Study ID Numbers: | B1451017 |
| Study First Received: | July 1, 2009 |
| Last Updated: | November 17, 2009 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Pfizer:
|
Drug Interactions pharmacokinetics CYP2D6 |
CYP2C19 ketoconazole omeprazole |
Additional relevant MeSH terms:
|
Alzheimer Disease Huntington Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Tauopathies Neurodegenerative Diseases Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Basal Ganglia Diseases Chorea Dyskinesias Movement Disorders |
Heredodegenerative Disorders, Nervous System Genetic Diseases, Inborn Cognition Disorders Ketoconazole Omeprazole 14-alpha Demethylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antifungal Agents Anti-Infective Agents Therapeutic Uses Anti-Ulcer Agents Gastrointestinal Agents |
ClinicalTrials.gov processed this record on May 22, 2013