Abuse Potential Assessment of Intranasally Administered EMBEDA Compared To Morphine Sulfate Controlled Release And Placebo
Phase 1
Completed
- Conditions
- Narcotic AbuseOpioid-related DisordersAnalgesiaChronic Pain
- Interventions
- Registration Number
- NCT01595867
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 33
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment A Placebo Placebo Treatment B EMBEDA - morphine sulfate/ naltrexone hydrochloride EMBEDA 30 mg crushed Treatment C morphine sulfate CR crushed. Morphine Sulfate Controlled Release 30 mg crushed
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 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 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