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

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

Dimebon will not exhibit abuse potential when compared to placebo or a positive control (alprazolam).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease; Huntington's Disease
• Intervention / Treatment: Drug: dimebon; Drug: dimebon; Drug: dimebon; Drug: placebo; Drug: alprazolam; Drug: alprazolam

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo	Drug: placebo; Oral tablet or capsule; placebo, single dose
EXPERIMENTAL: dimebon 20 mg	Drug: dimebon; Oral tablet; 20 mg dimebon, single dose; Drug: dimebon; Oral tablet; 40 mg dimebon, single dose; Drug: dimebon; Oral tablet; 60 mg dimebon, single dose
EXPERIMENTAL: dimebon 40 mg	Drug: dimebon; Oral tablet; 20 mg dimebon, single dose; Drug: dimebon; Oral tablet; 40 mg dimebon, single dose; Drug: dimebon; Oral tablet; 60 mg dimebon, single dose
EXPERIMENTAL: dimebon 60 mg	Drug: dimebon; Oral tablet; 20 mg dimebon, single dose; Drug: dimebon; Oral tablet; 40 mg dimebon, single dose; Drug: dimebon; Oral tablet; 60 mg dimebon, single dose
ACTIVE_COMPARATOR: alprazolam 1 mg	Drug: alprazolam; Oral capsule; 1 mg alprazolam, single dose; Drug: alprazolam; Oral capsule; 3 mg alprazolam, single dose
ACTIVE_COMPARATOR: alprazolam 3 mg	Drug: alprazolam; Oral capsule; 1 mg alprazolam, single dose; Drug: alprazolam; Oral capsule; 3 mg alprazolam, single dose

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

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Medivation, Inc.

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): February 1, 2010
• Study Completion (ACTUAL): February 1, 2010

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (ESTIMATE): September 11, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 2, 2013
• Last Update Submitted That Met QC Criteria: February 20, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: oral single-dose 6-way crossover recreational drug users abuse potential pharmacodynamics safety
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Tauopathies; Cognition Disorders; Chorea; Alzheimer Disease; Huntington Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Alprazolam
• Other Study ID Numbers: B1451037