A Study In Healthy Volunteers To Estimate The Pharmacokinetics Of Four Modified-Release Formulations Of Dimebon (Latrepirdine)

Study Overview
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Brief Summary
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This study will evaluate four different modified release formulation to estimate the amount of dimebon available to the body relative to the current dimebon formulation that is given three times a day. The results of this study will help inform and guide further formulation development efforts with the ultimate goal of reducing dose frequency to once-a-day or twice-a-day.

Official Title
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A Phase 1, Randomized, Open-Label, Single Dose Cross-Over Study In Healthy Volunteers To Estimate The Pharmacokinetics Of Four Modified-Release Formulations Of Dimebon (Latrepirdine)

Conditions
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Alzheimer's Disease, Huntington Disease

Intervention / Treatment
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* Drug: Dimebon IR Tablet
* Drug: Dimebon MR1
* Drug: Dimebon MR2
* Drug: Dimebon MR3
* Drug: Dimebon MR4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Subjects with any history of a previous seizure (including childhood febrile seizures) or convulsion or significant head trauma. Subjects with hypersensitivity reactions to dimebon or other antihistamines. Any condition possibly affecting drug absorption (eg, gastrectomy). Smokers who use greater than 5 cigarettes per day. Use of proton pump inhibitors, antacids, and H2-blockers are prohibited for the duration of the study. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1<br> | Drug: Dimebon IR Tablet<br>* Pharmacokinetics of a single oral dose of 10 mg dimebon immediate release tablet will be assessed on Day 1 - 3.<br>|
| Experimental: Period 2<br> | Drug: Dimebon MR1<br>* Pharmacokinetics of a single oral dose of 10 mg dimebon modified release formulation, MR1, will be assessed on Day 1 - 3.<br>|
| Experimental: Period 3<br> | Drug: Dimebon MR2<br>* Pharmacokinetics of a single oral dose of 10 mg dimebon modified release formulation, MR2, will be assessed on Day 1 - 3.<br>|
| Experimental: Period 4<br> | Drug: Dimebon MR3<br>* Pharmacokinetics of a single oral dose of 10 mg dimebon modified release formulation, MR3, will be assessed on Day 1 - 3.<br>|
| Experimental: Period 5<br> | Drug: Dimebon MR4<br>* Pharmacokinetics of a single oral dose of 10 mg dimebon modified release formulation, MR4, will be assessed on Day 1 - 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK endpoints for dimebon and M7 (where appropriate) for each formulation: AUC0-24, AUC0-24(dn), AUCinf (as data permit) AUCinf(dn), AUClast, AUClast(dn), Tlag, Cmax, Tmax, and t1/2 (as data permit). |  | Day 1-3 of Period 1, 2, 3, 4, or 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability for each formulation (AEs, ECG, vital signs, safety labs) |  | Day 1-3 of Period 1, 2, 3, 4, or 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioavailability pharmacokinetics Alzheimer's Disease Huntington Disease