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

NCT00931073 | Completed Phase 1

• 1 other identifier: B1451017
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease; Huntington's Disease

Keywords

Drug Interactions; pharmacokinetics; CYP2D6; CYP2C19; ketoconazole; omeprazole

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• 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

Study Arms (3)

Period 1

EXPERIMENTAL

Drug: Dimebon alone

Period 2

EXPERIMENTAL

Drug: Dimebon + Ketoconazole

Period 3

EXPERIMENTAL

Drug: Dimebon + Omeprazole

Interventions

Dimebon alone DRUG

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

Period 1

Dimebon + Ketoconazole DRUG

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

Period 2

Dimebon + Omeprazole DRUG

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

Period 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• Medivation, Inc.: collaborator

Study Sites (1)

Pfizer Investigational Site

Kalamazoo, Michigan, 49007, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Alzheimer Disease; Huntington Disease

Interventions

latrepirdine; Ketoconazole; Omeprazole

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Basal Ganglia Diseases; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: July 1, 2009
• First Posted: July 2, 2009
• Study Start: July 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: November 18, 2009

Record last verified: 2009-11

Locations

US (1)