Abuse Potential Assessment of Intranasally Administered EMBEDA Compared To Morphine Sulfate Controlled Release And Placebo

Study Overview
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Brief Summary
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This was a single-dose, randomized, double-blind, placebo-controlled, 3 way crossover study designed to evaluate the relative abuse potential of crushed EMBEDA® compared to morphine sulfate CR tablets and placebo in healthy male and female, non-dependent, recreational opioid users. An appropriate dose of morphine sulfate CR (i.e., 30 mg, 60 or 90 mg) was to be selected during Part A of the study (Dose Selection Phase). Each subject participated in the study for up to (approximately) 16 weeks and was confined in the clinic for a total of up to 12 nights.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, 3 Way Crossover Study Evaluating The Relative Abuse Potential Of Crushed Embeda Compared To Morphine Sulfate Controlled Release Tablets (Crushed) And Placebo In Non-Dependent, Recreational Opioid Users Following Intranasal Administration

Conditions
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Narcotic Abuse, Opioid-related Disorders, Analgesia, Chronic Pain

Intervention / Treatment
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* Drug: Placebo
* Drug: EMBEDA - morphine sulfate/ naltrexone hydrochloride
* Drug: morphine sulfate CR crushed.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects 18 to 55 years of age, inclusive. Subject is a recreational opioid user who is NOT dependent on opioids based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria and the Naloxone Challenge. A recreational opioid user is defined as use of opioids for non-therapeutic purposes (i.e., for psychoactive effects) on at least 10 occasions within the last year and at least once in the 12 weeks before the Screening Visit (Visit 1). Subjects must have experience with intranasal drug administration, defined as intranasal use on at least 3 occasions within the last year prior to the Screening Visit. Exclusion Criteria: Diagnosis of substance and/or alcohol dependence (excluding caffeine and nicotine), as assessed by the Investigator using the DSM IV-TR criteria. Has participated in, is currently participating in, or is seeking treatment for substance- and or alcohol-related disorders (excluding nicotine and caffeine). Has any condition in which an opioid is contraindicated; e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, or is suspected of having paralytic ileus. Allergy or history of hypersensitivity to morphine sulfate, other opioids, naltrexone hydrochloride, naloxone, and/or lactose. History or current clinically significant neurological, cardiovascular, renal, hepatic, endocrine, gastrointestinal, hematologic, or metabolic disease as evaluated by the Investigator. History or current pulmonary disease including asthma, chronic obstructive pulmonary disease, exercise-induced asthma, bronchitis, and obstructive sleep apnea.

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment A<br>Placebo | Drug: Placebo<br>* Lactose (100 mg) placebo tablets crushed; single dose<br>|
| Experimental: Treatment B<br>EMBEDA 30 mg crushed | Drug: EMBEDA - morphine sulfate/ naltrexone hydrochloride<br>* EMBEDA (morphine sulfate/naltrexone hydrochloride) 30 mg/ 1.2 mg extended release; capsule contents crushed; single dose<br>|
| Active Comparator: Treatment C<br>Morphine Sulfate Controlled Release 30 mg crushed | Drug: morphine sulfate CR crushed.<br>* Morphine sulfate controlled release 30 mg tablet crushed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking Visual Analog Scale maximum peak effect (Emax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Drug Liking Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High Visual Analog Scale maximum peak effect (Emax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Drug Liking Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Drug Liking Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Drug Liking Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Drug Liking Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Drug Liking Visual Analog Scale Area time to maximum effect (TEmax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High VVisual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| High Visual Analog Scale Area time to maximum effect (TEmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale maximum peak effect (Emax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Any Drug Effects Visual Analog Scale Area time to maximum effect (TEmax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale maximum peak effect (Emax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Good Drug Effects Visual Analog Scale Area time to maximum effect (TEmax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale maximum peak effect (Emax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Bad Drug Effects Visual Analog Scale Area time to maximum effect (TEmax) |  | 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale maximum peak effect (Emax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Feel Sick Visual Analog Scale Area time to maximum effect (TEmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale maximum peak effect (Emax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Nausea Visual Analog Scale Area time to maximum effect (TEmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale maximum peak effect (Emax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Sleepy Visual Analog Scale Area time to maximum effect (TEmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale maximum peak effect (Emax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Dizzy Visual Analog Scale Area time to maximum effect (TEmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter minimum peak effect (Emin) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter time to minimum peak effect (TEmin) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter Area under the effect curve to 1 hour (AUE0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter Area under the effect curve to 2 hours (AUE0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter Area under the effect curve to 4 hours (AUE0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter Area under the effect curve to 8 hours (AUE0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter Area under the effect curve to 12 hours (AUE0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Pupil Diameter Area under the effect curve to 24 hours (AUE0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, and 24 hours post-dose | 
| Take Drug Again Visual Analog Scale maximum peak effect (Emax) |  | 12 and 24 hours post dose | 
| Take Drug Again Visual Analog Scale mean (Emean) |  | 12 and 24 hours post dose | 
| Overall Drug Liking Visual Analog Scale maximum peak effect (Emax) |  | 12 and 24 hours post dose | 
| Overall Drug Liking Visual Analog Scale mean (Emean) |  | 12 and 24 hours post dose | 
| Subject Rating Scale - Need to Blow Nose maximum peak effect (Emax) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Need to Blow Nose Area under the effect curve to 1 hour (AUE0-1h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Need to Blow Nose Area under the effect curve to 2 hours (AUE0-2h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Runny Nose/Nasal Discharge maximum peak effect (Emax) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Runny Nose/Nasal Discharge Area under the effect curve to 1 hour (AUE0-1h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Runny Nose/Nasal Discharge Area under the effect curve to 2 hours (AUE0-2h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Burning maximum peak effect (Emax) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Burning Area under the effect curve to 1 hour (AUE0-1h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Burning Area under the effect curve to 2 hours (AUE0-2h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Facial Pain/Pressure maximum peak effect (Emax) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Facial Pain/Pressure Area under the effect curve to 1 hour (AUE0-1h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Facial Pain/Pressure Area under the effect curve to 2 hours (AUE0-2h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Nasal Congestion maximum peak effect (Emax) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Nasal Congestion Area under the effect curve to 1 hour (AUE0-1h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Subject Rating Scale - Nasal Congestion Area under the effect curve to 2 hours (AUE0-2h) |  | pre dose and 0.5, 1, 1.5, and 2 hours post dose | 
| Plasma morphine - Maximum observed plasma concentration (Cmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Time to maximum observed plasma concentration (Tmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Area under the plasma concentration time curve from time zero to 1 hour (AUC0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Area under the plasma concentration time curve from time zero to 2 hours (AUC0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Area under the plasma concentration time curve from time zero to 4 hours (AUC0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol - Maximum observed plasma concentration (Cmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 1 hour (AUC0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 12 hours (AUC0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 24 hours (AUC0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 4 hours (AUC0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 8 hours (AUC0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol - Time to maximum observed plasma concentration (Tmax |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol- Area under the plasma concentration time curve from time zero to 2 hours (AUC0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma 6-ß-naltrexol- Area under the plasma concentration time curve from time zero to infinity (AUC0-8), as applicable |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Area under the plasma concentration time curve from time zero to 12 hours (AUC0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Area under the plasma concentration time curve from time zero to 24 hours (AUC0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Area under the plasma concentration time curve from time zero to 8 hours (AUC0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma morphine - Area under the plasma concentration time curve from time zero to infinity (AUC0-8), as applicable |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Area under the plasma concentration time curve from time zero to 1 hour (AUC0-1h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Area under the plasma concentration time curve from time zero to 12 hours (AUC0-12h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Area under the plasma concentration time curve from time zero to 24 hours (AUC0-24h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Area under the plasma concentration time curve from time zero to 4 hours (AUC0-4h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Area under the plasma concentration time curve from time zero to 8 hours (AUC0-8h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Area under the plasma concentration time curve from time zero to infinity (AUC0-8), as applicable |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Maximum observed plasma concentration (Cmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone - Time to maximum observed plasma concentration (Tmax) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Plasma naltrexone- Area under the plasma concentration time curve from time zero to 2 hours (AUC0-2h) |  | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
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abuse liability, abuse potential, morphine, intranasal administration, snorting, opioid abuse, pharmacodynamic, recreational drug use