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

NCT01595867 | Completed Phase 1

• 2 other identifiers: ALO-01-10-4004B4541005
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Narcotic Abuse; Opioid-related Disorders; Analgesia; Chronic Pain

Keywords

abuse liability; abuse potential; morphine; intranasal administration; snorting; opioid abuse; pharmacodynamic; recreational drug use

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (122)

• 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

Study Arms (3)

Treatment A

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Treatment B

EXPERIMENTAL

EMBEDA 30 mg crushed

Drug: EMBEDA - morphine sulfate/ naltrexone hydrochloride

Treatment C

ACTIVE COMPARATOR

Morphine Sulfate Controlled Release 30 mg crushed

Drug: morphine sulfate CR crushed.

Interventions

Placebo DRUG

Lactose (100 mg) placebo tablets crushed; single dose

Treatment A

EMBEDA - morphine sulfate/ naltrexone hydrochloride DRUG

EMBEDA (morphine sulfate/naltrexone hydrochloride) 30 mg/ 1.2 mg extended release; capsule contents crushed; single dose

Treatment B

morphine sulfate CR crushed. DRUG

Morphine sulfate controlled release 30 mg tablet crushed

Treatment C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Related Publications (1)

• 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.

  PMID: 23936895 DERIVED

Related Links

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

MeSH Terms

Conditions

Narcotic-Related Disorders; Opioid-Related Disorders; Agnosia; Chronic Pain; Recreational Drug Use

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Behavior

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2012
• First Posted: May 10, 2012
• Study Start: August 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: June 8, 2012

Record last verified: 2012-06