Clinical trial NCT01775189: A Study to Characterize the Abuse Liability of ALO-02 in Healthy, Non-Dependent, Recreational Opioid Users When ALO-02 Capsules Are Crushed and Snorted
Official title: A Randomized, Double-blind, Placebo Controlled, Single-dose, 4-way Crossover Study To Determine The Relative Abuse Potential Of Alo-02 (Oxycodone Hydrochloride And Naltrexone Hydrochloride Extended Release Capsules) Compared To Oxycodone Immediate Release, And Placebo When Administered Intranasally To Non-dependent, Recreational Opioid Users.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Relative abuse potential study
Chronic pain
oxycodone
naltrexone
opioid-related disorders
drug abusers
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2013-01-24
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The main purpose of this study is to determine if oxycodone and naltrexone combination capsules (ALO-02) have the potential to be abused when they are crushed and snorted.

Detailed description: Abuse Liability Study

Eligibility criteria: Inclusion Criteria:

* Healthy subjects
* Non-dependent, recreational opioid users. (Must use opioid for non-therapeutic purposes on at least 10 occassions within the last year and at least once in the 8 weeks before Visit 1 (Screening Visit).
* Must have experience with intranasal opioid administration (snorted opioid drugs on at least 3 occassions within the last year before Visit 1 (Screening Visit).

Exclusion Criteria:

* Diagnosis of substance and/or alcohol dependence
* Subject has participated in, is currently participating in, or seeking treatment for substance and/or alcohol related disorder.

Primary outcomes:
measure: Drug Liking: Peak Effect (Emax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Drug Liking: Area Under Effect Curve (AUE) From 0-2 Hour
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2 hours post-dose
measure: High: Peak Effect (Emax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: High: Area Under Effect Curve (AUE) From 0-2 Hour
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2 hours post-dose
Secondary outcomes:
measure: Take Drug Again: Peak Effect (Emax)
timeFrame: Intervention period: 12, 24 hours post-dose
measure: Take Drug Again: Mean Effect (Emean)
timeFrame: Intervention period: 12, 24 hours post-dose
measure: Take Drug Again Effect at Hours 12 and 24
timeFrame: Intervention period: 12, 24 hours post-dose
measure: Overall Drug Liking: Peak Effect (Emax)
timeFrame: Intervention period: 12, 24 hours post-dose
measure: Overall Drug Liking: Mean Effect (Emean)
timeFrame: Intervention period: 12, 24 hours post-dose
measure: Overall Drug Liking Effect at Hours 12 and 24
timeFrame: Intervention period: 12, 24 hours post-dose
measure: Any Drug Effects: Peak Effect (Emax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Any Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Any Drug Effects: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Good Drug Effects: Peak Effect (Emax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Good Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Good Drug Effects: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Bad Drug Effects: Peak Effect (Emax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Bad Drug Effects: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Bad Drug Effects: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Feel Sick: Peak Effect (Emax)
timeFrame: Intervention periods: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Feel Sick: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Feel Sick: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Nausea: Peak Effect (Emax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Nausea: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Nausea: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Sleepy: Peak Effect (Emax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Sleepy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Sleepy: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Dizzy: Peak Effect (Emax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Dizzy: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Dizzy: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Percentage of Dose (Drug Powder) Insufflated
timeFrame: Intervention period: 0 Hour post-dose
measure: Pupillometry: Peak Effect (Emax)
timeFrame: Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Pupillometry: Area Under Effect Curve (AUE) From 0-1 Hour, 0-2 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Pupillometry: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
Other outcomes:
measure: Drug Liking: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour and 0-24 Hour
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Drug Liking: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: High: Area Under Effect Curve (AUE) From 0-1 Hour, 0-8 Hour and 0-24 Hours
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: High: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Subject Rating Scale for Nasal Effects: Peak Effect (Emax)
timeFrame: Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2 hours post-dose
measure: Subject Rating Scale for Nasal Effects: Area Under Effect Curve (AUE) From 0-1 Hour and 0-2 Hour
timeFrame: Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2 hours post-dose
measure: Subject Rating Scale for Nasal Effects: Time to Maximum (Peak) Effect (TEmax)
timeFrame: Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Oxycodone, Oxymorphone and Noroxycodone
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Naltrexone and 6-beta-naltrexol
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Oxycodone, Oxymorphone and Noroxycodone
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Naltrexone and 6-beta-naltrexol
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Plasma Decay Half-Life (t1/2) of Oxycodone, Oxymorphone and Noroxycodone
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Plasma Decay Half-Life (t1/2) of Naltrexone and 6-beta-naltrexol
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour and 0-8 Hour of Oxycodone, Oxymorphone and Noroxycodone
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8 hours post-dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Oxycodone, Oxymorphone and Noroxycodone
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Oxycodone, Oxymorphone and Noroxycodone
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Area Under the Concentration-Time Curve (AUC) From 0-1 Hour, 0-2 Hour and 0-8 Hour of Naltrexone and 6-beta-naltrexol
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8 hours post-dose
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Naltrexone and 6-beta-naltrexol
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Naltrexone and 6-beta-naltrexol
timeFrame: Intervention period: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Screening up to 3 to 7 days following last study drug administration, or time of early withdrawal
measure: Number of Participants With Clinically Significant Change in Vital Sign Examinations
timeFrame: Screening up to 3 to 7 days following last study drug administration, or time of early withdrawal
measure: Number of Participants With Clinically Significant Change in End Tidal Carbon Dioxide (EtCO2)
timeFrame: Intervention period: pre-dose, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose
measure: Number of Participants With Clinically Significant Change in Oxygen Saturation of Hemoglobin (SpO2)
timeFrame: Drug discrimination phase: pre-dose up to 5 hours; intervention period: pre-dose up to 12 hours
Locations:
city: Toronto
country: Canada
facility: INC Research Toronto Inc.
state: Ontario
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Setnik B, Bramson C, Bass A, Levy-Cooperman N, Malhotra B, Matschke K, Sommerville KW, Wolfram G, Geoffroy P. Intranasal administration of crushed ALO-02 (extended-release oxycodone with sequestered naltrexone): A randomized, controlled abuse-potential study in nondependent recreational opioid users. J Clin Pharmacol. 2015 Dec;55(12):1351-61. doi: 10.1002/jcph.552. Epub 2015 Jul 2.