Study to Evaluate the Subjective Effects of PTI-801 in Non-Physically Dependent Subjects With a History of Drug Abuse
This is a single-center, randomized, 7-way crossover, double-blind, active and placebo-controlled study to evaluate the subjective effects of oxycodone combined with ultra-low dose naltrexone in comparison to oxycodone alone in non-physically dependent subjects with a history of opioid abuse. Approximately 14 subjects will be randomized to one of fourteen sequences selected from a balanced 7x7 Latin square design and its mirror image.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Single-Center, Randomized, Double-Blind, Active- and Placebo-Controlled Crossover Study to Evaluate the Subjective Effects of PTI-801 in Non-Physically Dependent Subjects With a History of Drug Abuse|
- The primary objective of this study is to evaluate the subjective effects of PTI-801 formulated with either 0.001 mg naltrexone or 0.0001 mg naltrexone compared to oxycodone alone in individuals with a history of opioid abuse. [ Time Frame: At 30, 60, 90, 120, 150, 180 and 210 minutes post-dose ] [ Designated as safety issue: No ]
- Secondary objectives include determining the safety and physiological effects of single doses of PTI-801 compared to oxycodone following oral administration in individuals with a history of opioid abuse. [ Time Frame: At 30, 60, 90, 120, 150, 180 and 210 minutes post-dose ] [ Designated as safety issue: No ]
|Study Start Date:||August 2007|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Drug: oxycodone and naltrexone
tablets containing 20 mg or 40 mg oxycodone
/ tablets containing 20 mg or 40 mg oxycodone combined w/0.001 mg or 0.0001 mg naltrexone
At the conclusion of a screening period, qualifying subjects with a negative urine drug screen and ethanol breath test will be admitted to an inpatient research unit. After a 24 hour observation period confirming that the subject is not undergoing opioid withdrawal, subjects will randomly receive either 30 mg oxycodone or matching placebo over two consecutive days in a double-blind fashion. The purpose of this oxycodone vs. placebo qualifying period is to select for subjects with a positive drug liking response and to orient subjects to the various scales. Only subjects with a positive response on the visual analog "Liking" scale of at least 20 points higher on active oxycodone vs. placebo will be eligible to continue in the double-blind 7-way crossover study. Fourteen subjects will be randomized to one of fourteen sequences.
Each subject will receive a single dose of one of the following 7 treatments:
Placebo, oxycodone 20 mg, oxycodone 40 mg, oxycodone 20 mg/naltrexone 0.001 mg, oxycodone 40 mg/naltrexone 0.001 mg,oxycodone 20 mg/naltrexone 0.0001 mg, oxycodone 40 mg/naltrexone 0.0001 mg.
Oxycodone and naltrexone will be formulated in combination as a single tablet. All tablets will be identical in appearance. The identity of each treatment will be unknown to all study personnel and subjects.
Immediately prior to and at specified time points after administration of a single dose of study drug, subjects will complete the following subjective scales: visual analog scales (VAS) for any drug effect, high, good effects, bad effects, liking, and sick; and adjective ratings (agonist and antagonist scales). Subjects will also be asked to complete a money versus drug questionnaire at various time points after drug administration. Observers will complete an adjective rating scale. Safety will be monitored by vital signs (heart rate, blood pressure, respiratory rate, and pulse oximetry), adverse events assessments, clinical laboratory tests, physical examinations and electrocardiograms (ECGs). In addition, pupil diameter (measured by photographs) will be obtained to monitor for physiological signs of opioid effects.
The first double-blind dose of study drug will be administered at least 24 hours after the last dose of the two day qualifying period. Dosings will be separated by a washout period of at least 120 hours (see sample calendar in Section 6.5). The observation period for safety will continue for 24 hours following the final dose of study drug.
|United States, Maryland|
|Behavioral Pharmacology Research Unit|
|Baltimore, Maryland, United States, 21224-6823|
|Principal Investigator:||George E Bigelow, PhD||Johns Hopkins School of Medicine|