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:
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

July 1, 2009
November 17, 2009
July 2009
October 2009   (final data collection date for primary outcome 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)) [ 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 ]
Same as current
Complete list of historical versions of study NCT00931073 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
  • Alzheimer's Disease
  • Huntington's Disease
  • 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
  • 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
  • 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
  • Experimental: Period 1
    Intervention: Drug: Dimebon alone
  • Experimental: Period 2
    Intervention: Drug: Dimebon + Ketoconazole
  • Experimental: Period 3
    Intervention: Drug: Dimebon + Omeprazole
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
October 2009
October 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00931073
B1451017
No
Director, Clinical Trial Disclosure Group, Pfizer, Inc.
Pfizer
Medivation, Inc.
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
November 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP