A Study to Characterize the Abuse Liability of ALO-02 in Healthy, Non-Dependent, Recreational Opioid Users When ALO-02 Capsules Are Crushed and Snorted

Study Overview
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Brief Summary
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The main purpose of this study is to determine if oxycodone and naltrexone combination capsules (ALO-02) have the potential to be abused when they are crushed and snorted.

Detailed Description
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Abuse Liability Study

Official Title
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A Randomized, Double-blind, Placebo Controlled, Single-dose, 4-way Crossover Study To Determine The Relative Abuse Potential Of Alo-02 (Oxycodone Hydrochloride And Naltrexone Hydrochloride Extended Release Capsules) Compared To Oxycodone Immediate Release, And Placebo When Administered Intranasally To Non-dependent, Recreational Opioid Users.

Conditions
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Healthy

Intervention / Treatment
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* Drug: ALO-02 weight-matched placebo
* Drug: crushed ALO-02 30 mg/3.6 mg
* Drug: oxycodone weight-matched placebo
* Drug: crushed oxycodone IR 30 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects Non-dependent, recreational opioid users. (Must use opioid for non-therapeutic purposes on at least 10 occassions within the last year and at least once in the 8 weeks before Visit 1 (Screening Visit). Must have experience with intranasal opioid administration (snorted opioid drugs on at least 3 occassions within the last year before Visit 1 (Screening Visit). Exclusion Criteria: Diagnosis of substance and/or alcohol dependence Subject has participated in, is currently participating in, or seeking treatment for substance and/or alcohol related disorder.

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

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment A<br> | Drug: ALO-02 weight-matched placebo<br>* crushed sugar spheres (powder) x 1 dose<br>|
| Experimental: Treatment B<br> | Drug: crushed ALO-02 30 mg/3.6 mg<br>* crushed ALO-02 30 mg/3.6 mg capsule x 1 dose<br>|
| Placebo Comparator: Treatment C<br> | Drug: oxycodone weight-matched placebo<br>* crushed lactose tablets (powder) x 1 dose<br>|
| Active Comparator: Treatment D<br> | Drug: crushed oxycodone IR 30 mg<br>* Three (3) crushed immediate-release (IR) oxycodone 10 mg tablets x 1 dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking: Peak Effect (Emax) | Drug liking 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 VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the extreme left with strong disliking (score of 0 mm) and on the extreme right with strong liking (score of 100 mm). Peak Effect (Emax) = Maximum observed score. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour | Drug liking 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 VAS anchored in the center with a neutral anchor of neither like nor dislike (score of 50 mm), on the extreme left with strong disliking (score of 0 mm) and on the extreme right with strong liking (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2 hours post-dose | 
| High: Peak Effect (Emax) | High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| High: Area Under Effect Curve (AUE) From 0-2 Hour | High VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Take Drug Again: Peak Effect (Emax) | Take drug again VAS 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 VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emax = Maximum observed score. | Intervention period: 12, 24 hours post-dose | 
| Take Drug Again: Mean Effect (Emean) | Take drug again VAS 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 VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). Emean = Average observed score. | Intervention period: 12, 24 hours post-dose | 
| Take Drug Again Effect at Hours 12 and 24 | Take drug again VAS 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 VAS with score ranging from 0 mm to 100 mm (score of 0 mm = definitely would not, 50 mm = do not care, and 100 mm = definitely would). | Intervention period: 12, 24 hours post-dose | 
| Overall Drug Liking: Peak Effect (Emax) | Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm 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 = Maximum observed score. | Intervention period: 12, 24 hours post-dose | 
| Overall Drug Liking: Mean Effect (Emean) | Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm 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). Emean = Average observed score. | Intervention period: 12, 24 hours post-dose | 
| Overall Drug Liking Effect at Hours 12 and 24 | Overall drug liking VAS assesses the participant's global perception of drug liking (that is, effects over the whole course of the drug experience including any carry-over effects). A 100 mm 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). | Intervention period: 12, 24 hours post-dose | 
| Any Drug Effects: Peak Effect (Emax) | Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Any Drug Effects: Time to Maximum (Peak) Effect (TEmax) | Any Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Good Drug Effects: Peak Effect (Emax) | Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Good Drug Effects: Time to Maximum (Peak) Effect (TEmax) | Good Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Bad Drug Effects: Peak Effect (Emax) | Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax) | Bad Drug Effects VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Feel Sick: Peak Effect (Emax) | Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention periods: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Feel Sick: Time to Maximum (Peak) Effect (TEmax) | Feel Sick VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Nausea: Peak Effect (Emax) | Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Nausea: Time to Maximum (Peak) Effect (TEmax) | Nausea VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Sleepy: Peak Effect (Emax) | Sleepy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Sleepy VAS 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) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Sleepy: Time to Maximum (Peak) Effect (TEmax) | Sleepy VAS 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) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Dizzy: Peak Effect (Emax) | Dizzy VAS assesses the effect experienced by the participant on a 100 mm unipolar VAS, where responses are unidirectional and range from 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Dizzy VAS 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) to 'extremely' (score of 100 mm). AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Dizzy: Time to Maximum (Peak) Effect (TEmax) | Dizzy VAS 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) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Percentage of Dose (Drug Powder) Insufflated | The percentage of dose insufflated, was based on a calculation of the weight of powder remaining (if any) following each dosing during the intervention period. | Intervention period: 0 Hour post-dose | 
| Pupillometry: Peak Effect (Emax) | Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. Emax = Maximum observed score. | Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour | Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. AUE (0-x) = Area under the effect versus time curve from time zero to time of last quantifiable effect (0-x). | Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 
| Pupillometry: Time to Maximum (Peak) Effect (TEmax) | Pupillometry assessments measure change in pupil size (miosis) as an indicator of opioid pharmacological properties. Participants have the size of pupil measured using a pupillometer. Measurements are made in a dimly lit (mesopic) room with controlled lighting conditions. The same eye for each participant was used for all measurements during the study. TEmax = Time to maximum observed score. | Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relative abuse potential study, Chronic pain, oxycodone, naltrexone, opioid-related disorders, drug abusers