A Study To Evaluate The Abuse Potential Of Single Oral Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug Users

Study Overview
=================
Brief Summary
-----------------
Dimebon will not exhibit abuse potential when compared to placebo or a positive control (alprazolam).

Detailed Description
-----------------
The main purpose for this study is to determine whether dimebon exhibits abuse potential.

Official Title
-----------------
A Randomized, Double-Blind, Placebo- And Active-Controlled Single-Dose, Crossover Study To Evaluate The Abuse Potential Of Single Doses Of Dimebon (Latrepirdine) In Healthy Recreational Polydrug Users

Conditions
-----------------
Alzheimer's Disease, Huntington's Disease

Intervention / Treatment
-----------------
* Drug: dimebon
* Drug: dimebon
* Drug: dimebon
* Drug: placebo
* Drug: alprazolam
* Drug: alprazolam


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 55 years. Recreational polydrug user with a history of CNS depressant use. Exclusion Criteria: History of clinically significant neurologic condition(s), such as seizures, convulsions, epilepsy, or significant head injury, as judged by the investigator or designee. A known history of hypersensitivity or previous intolerance to dimebon or other antihistamines. Self-reported history of drug or alcohol dependence (except nicotine or caffeine) in the 2 years prior to screening, or drug or alcohol dependence as defined by the (DSM-IV-TR) in 12 months prior to screening, including subjects who have ever been in a substance rehabilitation program (other than treatment for smoking cessation). History of clinically significant psychiatric disorder(s), as judged by the investigator or qualified designee.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dimebon 20 mg<br> | Drug: dimebon<br>* Oral tablet; 20 mg dimebon, single dose<br>|
| Experimental: dimebon 40 mg<br> | Drug: dimebon<br>* Oral tablet; 40 mg dimebon, single dose<br>|
| Experimental: dimebon 60 mg<br> | Drug: dimebon<br>* Oral tablet; 60 mg dimebon, single dose<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* Oral tablet or capsule; placebo, single dose<br>|
| Active Comparator: alprazolam 1 mg<br> | Drug: alprazolam<br>* Oral capsule; 1 mg alprazolam, single dose<br>|
| Active Comparator: alprazolam 3 mg<br> | Drug: alprazolam<br>* Oral capsule; 3 mg alprazolam, single dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Balance of Effects- Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Drug liking VAS is one of the measures of balance of effects that assesses the degree that a participant likes a drug effect at the time the question is being asked (that is, at the moment). It is scored using a 100 millimeter (mm) bipolar visual analogue scale (VAS) anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the left with strong disliking (score of 0 mm) and on the right with strong liking (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Balance of Effects- Overall Drug Liking VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Overall drug liking VAS is one of the measures of balance of effects that assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carryover effects). A 100 mm bipolar VAS is used to assess response based on a score ranging from 0 mm to 100 mm (0 mm = strong disliking, 50 mm= neither like nor dislike, and 100 mm= strong liking). Emax is the largest effect score between 6 to 24 hours post-dose. Emin is the smallest effect score between 6 to 24 hours post-dose. | 6, 12, 24 hours post-dose | 
| Balance of Effects- Take Drug Again VAS: Peak Effect (Maximum Effect [Emax]) | Take drug again VAS is one of the measures of balance of effects. It is a subjective assessment of the degree to which a participant would desire to take the drug again if given the opportunity. It is presented on a 100 mm bipolar VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely not, 50 mm = do not care, and 100 mm = definitely so). Emax is largest effect score between 6 hours to 24 hours. | 6, 12, 24 hours post-dose | 
| Balance of Effects- Good and Bad Effects VAS: Peak Effect (Maximum Effect [Emax]) and Minimum Effect (Emin) | Good and Bad effects VAS is one of the measures of balance of effects that assesses the effect experienced by the participant on a 100 mm bipolar VAS, anchored in the center with a neutral anchor of neither good nor bad effects (score of 50 mm), on the left with bad effects(score of 0 mm) and on the right with good effects (score of 100 mm). Emax is largest effect score between 0.5 to 24 hours post-dose. Emin is smallest effect score between 0.5 to 24 hours post-dose. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Balance of Effects- Subjective Drug Value (SDV): Maximum Effect (Emax) | SDV is one of measures of balance of effects. It is a proxy measure of reinforcing efficacy that involves a series of independent, theoretical forced choices between drug administered and different monetary values. Participants were asked to choose between receiving another dose of same drug or an envelope containing specified amount of money, but they did not receive drug or money as described. Possible score range from 0.25 to 50. Higher score range indicates higher SDV. Emax: largest effect score between 6-24 hours post-dose. | 6, 12, 24 hrs post-dose | 
| Positive Effects- Addiction Research Center Inventory (ARCI) Morphine Benzedrine Group (MBG): Maximum Effect (Emax) | ARCI (MBG) is one of the measures of positive effects. It is a set of 16 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to the scoring direction. Score range: 0 to 16, higher score indicated positive effects. Emax: largest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 12, 24 hours post-dose | 
| Positive Effects- Good Drug Effects: Peak Effect (Maximum Effect [Emax]) | Good drug effects VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Positive Effects- High VAS: Peak Effect (Maximum Effect [Emax]) | High VAS is one of the measures of positive effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0 to 24 hours. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Negative Effects- Bad Drug Effects: Peak Effect (Maximum Effect [Emax]) | Bad effects VAS is one of the measures of negative effects that assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is largest effect score between 0.5 to 24 hrs. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Negative Effects- Addiction Research Center Inventory (ARCI) Lysergic Acid Diethylamide (LSD): Maximum Effect (Emax) | ARCI (LSD) is one of the measures of negative effects. It is a set of 14 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when the answer is opposite to scoring direction. Score range: 0 to 14, higher score indicated higher negative effects. Emax: largest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Sedative Effects- Addiction Research Center Inventory (ARCI) Pentobarbital Chlorpromazine Group (PCAG): Maximum Effect (Emax) | ARCI (PCAG) is one of the measures of sedative effects. It is a set of 15 questions in which each question contributes to total score. Participants indicate their responses by selecting 'False' or 'True'. One point is given for each response that agrees with the scoring direction on scale i.e, true items receive a score of 1 if answer is 'True', false items receive a score of 1 if answer is 'False'. No points are given when answer is opposite to scoring direction. Score range: 0 to 15, higher score indicated higher sedative effects. Emax: largest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Sedative Effects- Alertness/Drowsiness: Minimum Effect (Emin) | Alertness/Drowsiness VAS is one of the measures of sedative effects. It is scored using a 100 mm bipolar VAS anchored in the center with a neutral anchor of neither drowsy nor alert (score of 50 mm), on the left with very drowsy (score of 0 mm) and on the right with very alert (score of 100 mm). Emin is the smallest effect score between 0 to 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Other Subjective Effects- Any Drug Effects: Peak Effect (Maximum Effect [Emax]) | Any drug effects VAS is one of the measures of other subjective effects. It assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= definitely not) to 'extremely' (score of 100 mm= definitely so). Emax is the largest effect score between 0.5 to 24 hours post-dose. | 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Other Subjective Effects- Drug Similarity | Drug similarity VAS is one of the measures of other subjective effects. It assesses the similarity of the drug recently received by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from a response of 'none' (score of 0 mm= not at all similar) to 'extremely' (score of 100 mm= very similar). Recently received drugs were compared with placebo, benzodiazepines, codeine/morphine, Tetrahydrocannabinol (THC), pseudoephedrine. | 12 hours post-dose | 
| Other Subjective Effects- Addiction Research Center Inventory (ARCI) Benzedrine Group (BG): Maximum Effect (Emax) and Minimum Effect (Emin) | ARCI (BG) is measure of other subjective effects. It is a set of 13 questions in which each question contributes to total score. Participants select 'False' / 'True' for response. One point given for each response that agrees with scoring direction, true items receive score of 1 if answer 'True', false items receive score of 1 if answer 'False'. No points if answer is opposite to scoring direction. Score range: 0 to 13, higher score indicated higher other subjective effects. Emax: largest effect score between 0 - 24 hours post-dose. Emin: smallest effect score between 0 - 24 hours post-dose. | 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oral single-dose 6-way crossover recreational drug users abuse potential pharmacodynamics safety