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.
Drug Liking Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)Drug Liking Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Drug Liking Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Drug Liking Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Drug Liking Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Drug Liking Visual Analog Scale Area time to maximum effect (TEmax)
High VVisual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
High Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
High Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
High Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
High Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
High Visual Analog Scale Area time to maximum effect (TEmax)
Any Drug Effects Visual Analog Scale maximum peak effect (Emax)
Any Drug Effects Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h)
Any Drug Effects Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
Any Drug Effects Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Any Drug Effects Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Any Drug Effects Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Any Drug Effects Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Any Drug Effects Visual Analog Scale Area time to maximum effect (TEmax)
Good Drug Effects Visual Analog Scale maximum peak effect (Emax)
Good Drug Effects Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
Good Drug Effects Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h)
Good Drug Effects Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Good Drug Effects Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Good Drug Effects Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Good Drug Effects Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Good Drug Effects Visual Analog Scale Area time to maximum effect (TEmax)
Bad Drug Effects Visual Analog Scale maximum peak effect (Emax)
Bad Drug Effects Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
Bad Drug Effects Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h)
Bad Drug Effects Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Bad Drug Effects Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Bad Drug Effects Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Bad Drug Effects Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Bad Drug Effects Visual Analog Scale Area time to maximum effect (TEmax)
Feel Sick Visual Analog Scale maximum peak effect (Emax)
Feel Sick Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
Feel Sick Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h)
Feel Sick Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Feel Sick Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Feel Sick Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Feel Sick Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Feel Sick Visual Analog Scale Area time to maximum effect (TEmax)
Nausea Visual Analog Scale maximum peak effect (Emax)
Nausea Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
Nausea Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h)
Nausea Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Nausea Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Nausea Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Nausea Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Nausea Visual Analog Scale Area time to maximum effect (TEmax)
Sleepy Visual Analog Scale maximum peak effect (Emax)
Sleepy Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
Sleepy Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h)
Sleepy Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Sleepy Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Sleepy Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Sleepy Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Sleepy Visual Analog Scale Area time to maximum effect (TEmax)
Dizzy Visual Analog Scale maximum peak effect (Emax)
Dizzy Visual Analog Scale Area under the effect curve to 1 hour (AUE0-1h)
Dizzy Visual Analog Scale Area under the effect curve to 2 hours (AUE0-2h)
Dizzy Visual Analog Scale Area under the effect curve to 4 hours (AUE0-4h)
Dizzy Visual Analog Scale Area under the effect curve to 8 hours (AUE0-8h)
Dizzy Visual Analog Scale Area under the effect curve to 12 hours (AUE0-12h)
Dizzy Visual Analog Scale Area under the effect curve to 24 hours (AUE0-24h)
Dizzy Visual Analog Scale Area time to maximum effect (TEmax)
Pupil Diameter minimum peak effect (Emin)
Pupil Diameter time to minimum peak effect (TEmin)
Pupil Diameter Area under the effect curve to 1 hour (AUE0-1h)
Pupil Diameter Area under the effect curve to 2 hours (AUE0-2h)
Pupil Diameter Area under the effect curve to 4 hours (AUE0-4h)
Pupil Diameter Area under the effect curve to 8 hours (AUE0-8h)
Pupil Diameter Area under the effect curve to 12 hours (AUE0-12h)
Pupil Diameter Area under the effect curve to 24 hours (AUE0-24h)
Take Drug Again Visual Analog Scale maximum peak effect (Emax)
Take Drug Again Visual Analog Scale mean (Emean)
Overall Drug Liking Visual Analog Scale maximum peak effect (Emax)
Overall Drug Liking Visual Analog Scale mean (Emean)
Subject Rating Scale - Need to Blow Nose maximum peak effect (Emax)
Subject Rating Scale - Need to Blow Nose Area under the effect curve to 1 hour (AUE0-1h)
Subject Rating Scale - Need to Blow Nose Area under the effect curve to 2 hours (AUE0-2h)
Subject Rating Scale - Runny Nose/Nasal Discharge maximum peak effect (Emax)
Subject Rating Scale - Runny Nose/Nasal Discharge Area under the effect curve to 1 hour (AUE0-1h)
Subject Rating Scale - Runny Nose/Nasal Discharge Area under the effect curve to 2 hours (AUE0-2h)
Subject Rating Scale - Burning maximum peak effect (Emax)
Subject Rating Scale - Burning Area under the effect curve to 1 hour (AUE0-1h)
Subject Rating Scale - Burning Area under the effect curve to 2 hours (AUE0-2h)
Subject Rating Scale - Facial Pain/Pressure maximum peak effect (Emax)
Subject Rating Scale - Facial Pain/Pressure Area under the effect curve to 1 hour (AUE0-1h)
Subject Rating Scale - Facial Pain/Pressure Area under the effect curve to 2 hours (AUE0-2h)
Subject Rating Scale - Nasal Congestion maximum peak effect (Emax)
Subject Rating Scale - Nasal Congestion Area under the effect curve to 1 hour (AUE0-1h)
Subject Rating Scale - Nasal Congestion Area under the effect curve to 2 hours (AUE0-2h)
Plasma morphine - Maximum observed plasma concentration (Cmax)
Plasma morphine - Time to maximum observed plasma concentration (Tmax)
Plasma morphine - Area under the plasma concentration time curve from time zero to 1 hour (AUC0-1h)
Plasma morphine - Area under the plasma concentration time curve from time zero to 2 hours (AUC0-2h)
Plasma morphine - Area under the plasma concentration time curve from time zero to 4 hours (AUC0-4h)
Plasma 6-ß-naltrexol - Maximum observed plasma concentration (Cmax)
Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 1 hour (AUC0-1h)
Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 12 hours (AUC0-12h)
Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 24 hours (AUC0-24h)
Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 4 hours (AUC0-4h)
Plasma 6-ß-naltrexol - Area under the plasma concentration time curve from time zero to 8 hours (AUC0-8h)
Plasma 6-ß-naltrexol - Time to maximum observed plasma concentration (Tmax
Plasma 6-ß-naltrexol- Area under the plasma concentration time curve from time zero to 2 hours (AUC0-2h)
Plasma 6-ß-naltrexol- Area under the plasma concentration time curve from time zero to infinity (AUC0-8), as applicable
Plasma morphine - Area under the plasma concentration time curve from time zero to 12 hours (AUC0-12h)
Plasma morphine - Area under the plasma concentration time curve from time zero to 24 hours (AUC0-24h)
Plasma morphine - Area under the plasma concentration time curve from time zero to 8 hours (AUC0-8h)
Plasma morphine - Area under the plasma concentration time curve from time zero to infinity (AUC0-8), as applicable
Plasma naltrexone - Area under the plasma concentration time curve from time zero to 1 hour (AUC0-1h)
Plasma naltrexone - Area under the plasma concentration time curve from time zero to 12 hours (AUC0-12h)
Plasma naltrexone - Area under the plasma concentration time curve from time zero to 24 hours (AUC0-24h)
Plasma naltrexone - Area under the plasma concentration time curve from time zero to 4 hours (AUC0-4h)
Plasma naltrexone - Area under the plasma concentration time curve from time zero to 8 hours (AUC0-8h)
Plasma naltrexone - Area under the plasma concentration time curve from time zero to infinity (AUC0-8), as applicable
Plasma naltrexone - Maximum observed plasma concentration (Cmax)
Plasma naltrexone - Time to maximum observed plasma concentration (Tmax)
Plasma naltrexone- Area under the plasma concentration time curve from time zero to 2 hours (AUC0-2h)
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
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.