Abuse Potential of Orally Administered Crushed Embeda Compared to Crushed Controlled-Release Morphine and Placebo in Non-Dependent Recreational Opioid Users

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the abuse potential of EMBEDA compared to controlled release morphine when crushed and taken orally by non-dependent recreational opioid users; secondary purposes include to determine the abuse potential of crushed EMBEDA relative to placebo and and to compare the pharmacokinetics and safety of crushed EMBEDA with crushed controlled-release morphine and crushed placebo.

Official Title
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A Randomized, Double-Blind, Placebo- and Active-Controlled, 3-Way Crossover Study to Determine the Abuse Potential of Oral Administration of Crushed EMBEDA Relative to Crushed Controlled-Release Morphine Sulfate and Placebo in Non Dependent, Recreational Opioid Users

Conditions
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Nondependent Opioid Abuse, Episodic

Intervention / Treatment
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* Drug: Placebo
* Drug: MS Contin (morphine sulfate, controlled release)
* Drug: EMBEDA (morphine sulfate / naltrexone hydrochloride)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a recreational opioid user who is NOT physically 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 recreationally abusing 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 prior to Visit 1. Subject is in generally good health as determined by medical history, physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG). Exclusion Criteria: Has a history or current diagnosis of substance 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). History or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, which in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results. Has a known allergy or history of hypersensitivity to morphine sulfate, opioids in general, naltrexone hydrochloride (HCl) or similar compounds and/or the known excipients in the investigational drug products. 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). Females who are pregnant, lactating, or are planning to become pregnant during the course of the study. Females with a positive serum pregnancy test at Visit 1 or at any subsequent study visit will be excluded from participating in the study.

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: Placebo<br> | Drug: Placebo<br>* Single-dose, 2 x microcrystalline cellulose (weighed to equal weights of average tablet/capsule of active comparator) mixed with 150 ml artificially sweetened, non-carbonated beverage<br>|
| Active Comparator: MS Contin (morphine sulfate, controlled release)<br> | Drug: MS Contin (morphine sulfate, controlled release)<br>* Single-dose, 2 x 60 mg morphine sulfate whole tablets manually crushed and mixed with 150 ml artificially sweetened, non-carbonated beverage<br>|
| Experimental: EMBEDA (morphine sulfate / naltrexone hydrochloride)<br> | Drug: EMBEDA (morphine sulfate / naltrexone hydrochloride)<br>* Single-dose, solution 2 x 60 mg morphine sulfate with sequestered 2.4 mg Naltrexone hydrochloride whole capsules manually crushed and mixed with 150 ml artificially sweetened, non-carbonated beverage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hours | 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 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). AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hours (hrs) (0-2). | 0.5, 1, 1.5 and 2 hrs post-dose | 
| 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 mm bipolar 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 = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| High: Area Under Effect Curve (AUE) From 0-2 Hours | High 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | 0.5, 1, 1.5 and 2 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Liking: Area Under Effect Curve (AUE) From 0-1 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 mm bipolar 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). AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | 0.5 and 1 hrs post-dose | 
| Drug Liking: Area Under Effect Curve (AUE) From 0-4 Hours | 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 mm bipolar 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). AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Drug Liking: Area Under Effect Curve (AUE) From 0-8 Hours | 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 mm bipolar 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). AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Drug Liking: Area Under Effect Curve (AUE) From 0-12 Hours | 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 mm bipolar 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). AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Drug Liking: Area Under Effect Curve (AUE) From 0-24 Hours | 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 mm bipolar 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). AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Drug Liking: Time to Maximum (Peak) Effect (TEmax) | 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 mm bipolar 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). TEmax = Time to maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| High: Area Under Effect Curve (AUE) From 0-1 Hour | High 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | 0.5 and 1 hrs post-dose | 
| High: Area Under Effect Curve (AUE) From 0-4 Hours | High 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| High: Area Under Effect Curve (AUE) From 0-8 Hours | High 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| High: Area Under Effect Curve (AUE) From 0-12 Hours | High 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| High: Area Under Effect Curve (AUE) From 0-24 Hours | High 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| High: Time to Maximum (Peak) Effect (TEmax) | High 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Good Effects: Area Under Effect Curve (AUE) From 0-1 Hour | Good effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | 0.5 and 1 hrs post-dose | 
| Good Effects: Area Under Effect Curve (AUE) From 0-2 Hours | Good effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | 0.5, 1, 1.5 and 2 hrs post-dose | 
| Good Effects: Area Under Effect Curve (AUE) From 0-4 Hours | Good effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Good Effects: Area Under Effect Curve (AUE) From 0-8 Hours | Good effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Good Effects: Area Under Effect Curve (AUE) From 0-12 Hours | Good effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Good Effects: Area Under Effect Curve (AUE) From 0-24 Hours | Good effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Good Effects: Peak Effect (Emax) | Good effects 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). Emax = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Good Effects: Time to Maximum (Peak) Effect (TEmax) | Good effects 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Any Effects: Area Under Effect Curve (AUE) From 0-1 Hour | Any effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | 0.5 and 1 hrs post-dose | 
| Any Effects: Area Under Effect Curve (AUE) From 0-2 Hours | Any effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | 0.5, 1, 1.5 and 2 hrs post-dose | 
| Any Effects: Area Under Effect Curve (AUE) From 0-4 Hours | Any effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Any Effects: Area Under Effect Curve (AUE) From 0-8 Hours | Any effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Any Effects: Area Under Effect Curve (AUE) From 0-12 Hours | Any effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Any Effects: Area Under Effect Curve (AUE) From 0-24 Hours | Any effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Any Effects: Peak Effect (Emax) | Any effects 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). Emax = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Any Effects: Time to Maximum (Peak) Effect (TEmax) | Any effects 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Bad Effects: Area Under Effect Curve (AUE) From 0-1 Hour | Bad effects 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | 0.5 and 1 hrs post-dose | 
| Bad Effects: Area Under Effect Curve (AUE) From 0-2 Hours | Bad effects 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | 0.5, 1, 1.5 and 2 hrs post-dose | 
| Bad Effects: Area Under Effect Curve (AUE) From 0-4 Hours | Bad effects 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Bad Effects: Area Under Effect Curve (AUE) From 0-8 Hours | Bad effects 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Bad Effects: Area Under Effect Curve (AUE) From 0-12 Hours | Bad effects 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Bad Effects: Area Under Effect Curve (AUE) From 0-24 Hours | Bad effects 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Bad Effects: Peak Effect (Emax) | Bad effects 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). Emax = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Bad Effects: Time to Maximum (Peak) Effect (TEmax) | Bad effects 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Nausea: Area Under Effect Curve (AUE) From 0-1 Hour | Nausea 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | Pre-dose, 0.5 and 1 hrs post-dose | 
| Nausea: Area Under Effect Curve (AUE) From 0-2 Hours | Nausea 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | 
| Nausea: Area Under Effect Curve (AUE) From 0-4 Hours | Nausea 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Nausea: Area Under Effect Curve (AUE) From 0-8 Hours | Nausea 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Nausea: Area Under Effect Curve (AUE) From 0-12 Hours | Nausea 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Nausea: Area Under Effect Curve (AUE) From 0-24 Hours | Nausea 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour | Feel sick 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | 0.5 and 1 hrs post-dose | 
| Feel Sick: Area Under Effect Curve (AUE) From 0-2 Hours | Feel sick 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | 0.5, 1, 1.5 and 2 hrs post-dose | 
| Feel Sick: Area Under Effect Curve (AUE) From 0-4 Hours | Feel sick 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Feel Sick: Area Under Effect Curve (AUE) From 0-8 Hours | Feel sick 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Feel Sick: Area Under Effect Curve (AUE) From 0-12 Hours | Feel sick 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Feel Sick: Area Under Effect Curve (AUE) From 0-24 Hours | Feel sick 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). TEmax = Time to maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Sleepy: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr(0-1). | 0.5 and 1 hrs post-dose | 
| Sleepy: Area Under Effect Curve (AUE) From 0-2 Hours | 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | 0.5, 1, 1.5 and 2 hrs post-dose | 
| Sleepy: Area Under Effect Curve (AUE) From 0-4 Hours | 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Sleepy: Area Under Effect Curve (AUE) From 0-8 Hours | 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Sleepy: Area Under Effect Curve (AUE) From 0-12 Hours | 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Sleepy: Area Under Effect Curve (AUE) From 0-24 Hours | 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Dizzy: Area Under Effect Curve (AUE) From 0-1 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 (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | 0.5 and 1 hrs post-dose | 
| Dizzy: Area Under Effect Curve (AUE) From 0-2 Hours | 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 (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | 0.5, 1, 1.5 and 2 hrs post-dose | 
| Dizzy: Area Under Effect Curve (AUE) From 0-4 Hours | 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 (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Dizzy: Area Under Effect Curve (AUE) From 0-8 Hours | 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 (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Dizzy: Area Under Effect Curve (AUE) From 0-12 Hours | 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 (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Dizzy: Area Under Effect Curve (AUE) From 0-24 Hours | 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 (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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 a response of 'none' (score of 0 mm) to 'extremely' (score of 100 mm). Emax = Maximum observed score. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs 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. | 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Overall Drug Liking Effect at 24 Hours | 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 carryover 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). | 24 hrs post dose | 
| Take Drug Again Effect at 24 Hours | 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). | 24 hrs post dose | 
| Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-1) = Area under the effect versus time curve from time 0 to 1 hr (0-1). | Pre-dose, 0.5 and 1 hrs post-dose | 
| Pupillometry: Area Under Effect Curve (AUE) From 0-2 Hours | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-2) = Area under the effect versus time curve from time 0 to 2 hrs (0-2). | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | 
| Pupillometry: Area Under Effect Curve (AUE) From 0-4 Hours | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-4) = Area under the effect versus time curve from time 0 to 4 hrs (0-4). | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Pupillometry: Area Under Effect Curve (AUE) From 0-8 Hours | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-8) = Area under the effect versus time curve from time 0 to 8 hrs (0-8). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Pupillometry: Area Under Effect Curve (AUE) From 0-12 Hours | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-12) = Area under the effect versus time curve from time 0 to 12 hrs (0-12). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Pupillometry: Area Under Effect Curve (AUE) From 0-24 Hours | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. AUE (0-24) = Area under the effect versus time curve from time 0 to 24 hrs (0-24). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Pupillometry: Peak Effect (Emax) | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. Emax = Smallest post-dose pupil size. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Pupillometry: Time to Maximum (Peak) Effect (TEmax) | Pupillometry assessments measured change in pupil size (miosis) as an indicator of opioid pharmacological properties. The same eye for each participant was used for all measurements during the study. Participants had the size of their pupil measured (in mm) using a pupillometer. Measurements were made in a dimly lit (mesopic) room with controlled lighting conditions. TEmax = Time to smallest post-dose pupil size. | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Morphine |  | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of Morphine |  | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Morphine | AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). | Pre-dose, 0.5 and 1 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Morphine | AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Morphine | AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Morphine | AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Morphine | AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Morphine | AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Morphine | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone |  | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of Naltrexone |  | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone | AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). | Pre-dose, 0.5 and 1 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone | AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone | AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone | AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone | AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone | AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone Metabolite (6-beta-naltrexol) |  | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of Naltrexone Metabolite (6-beta-naltrexol) |  | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-1)] of Naltrexone Metabolite (6-beta-naltrexol) | AUC (0-1) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-1). | Pre-dose, 0.5 and 1 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-2)] of Naltrexone Metabolite (6-beta-naltrexol) | AUC (0-2) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-2). | Pre-dose, 0.5, 1, 1.5 and 2 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-4)] of Naltrexone Metabolite (6-beta-naltrexol) | AUC (0-4) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-4). | Pre-dose, 0.5, 1, 1.5, 2, 3 and 4 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-8)] of Naltrexone Metabolite (6-beta-naltrexol) | AUC (0-8) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-8). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6 and 8 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-12)] of Naltrexone Metabolite (6-beta-naltrexol) | AUC (0-12) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-12). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hrs post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] of Naltrexone Metabolite (6-beta-naltrexol) | AUC (0-24) = Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration (0-24). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone Metabolite (6-beta-naltrexol) | AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞). | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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abuse potential, abuse liability, recreational opioid use, morphine