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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Analgesia; Opioid-related Disorders; Narcotic Abuse
• Intervention / Treatment: Drug: Placebo; Drug: EMBEDA - morphine sulfate/ naltrexone hydrochloride; Drug: morphine sulfate CR crushed.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Setnik B, Goli V, Levy-Cooperman N, Mills C, Shram M, Smith I. Assessing the subjective and physiological effects of intranasally administered crushed extended-release morphine formulations with and without a sequestered naltrexone core in recreational opioid users. Pain Res Manag. 2013 Jul-Aug;18(4):e55-62. doi: 10.1155/2013/952082.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: May 8, 2012
• First Submitted That Met QC Criteria: May 8, 2012
• First Posted (Estimate): May 10, 2012

Study Record Updates

• Last Update Posted (Estimate): June 8, 2012
• Last Update Submitted That Met QC Criteria: June 7, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: intranasal administration; abuse liability; morphine; pharmacodynamic; abuse potential; opioid abuse; snorting; recreational drug use
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Pain; Neurologic Manifestations; Chronic Pain; Opioid-Related Disorders; Narcotic-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Alcohol Deterrents; Naltrexone; Morphine
• Other Study ID Numbers: ALO-01-10-4004; B4541005