Healthy
Conditions
Keywords
Opioid, Recreational, Oxymorphone, Oxycodone, Extended Release, Healthy NonDependent Recreational Opioid Users
Brief summary
The purpose of this study is to compare the subjective and objective effects of Oxymorphone ER (Opana ER) versus Oxycodone CR (Oxycontin).
Interventions
DRUGOxymorphone ER
15mg or 30mg
DRUGOxycodone CR
30mg or 60mg
DRUGPlacebo
The placebo was a sugar pill.
DRUGHydromorphone
8 mg
Sponsors
Kendle Early Stage - Toronto
Endo Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Recreational opioid use. * At least 3 lifetime occasions of recreational use of an oral intact modified-release opioid product. * BMI within range of 19.0 to 29.9 kg/m2, inclusive, minimum weight of 50.0 kg at screening and Day 0 of treatment period 1
Exclusion criteria
* Self-reported history of drug or alcohol dependence in the past 2 years or presence of drug or alcohol dependence in the past 12 months as defined by the DSM-IV, including subjects who have ever been in a drug rehabilitation program. * Unwillingness or inability to abstain from recreational drug use as required for the study. * History of acute asthma or other obstructive airway disease or any condition that may increase the risk for respiratory depression, judged as clinically significant by the investigator or designee. * History of neurologic conditions such as convulsive disorders or severe head injury, judged as clinically significant by the investigator or qualified designee. * History of Addison's disease, hypothyroidism, pancreatitis, prostatic hypertrophy, or urethral stricture. * Use of non-prescription or prescription medications or natural health products within 7 days prior to first drug administration in the qualification phase and throughout the study, unless in the opinion of the investigator or designee, the product will not interfere with the study procedures or data integrity or compromise the safety of the subject. * Uses of Monoamine oxidize inhibitors (MAOIs) within 14 days of first drug administration in the qualification phase and throughout the study. * Current consumption of greater than 20 cigarettes (or 2 cigars) per day or inability to abstain from smoking (or use of any nicotine-containing sub stance) for at least 14 hours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High VAS - Emax (mm) | High VAS was administered at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose. | The High Visual Analog Scale (VAS) consisted of a horizontal line with a statement presented above the bar (I am feeling high). The ends of the line were marked with the descriptive anchors (Definitely not and Definitely so). Using a laptop computer, participants were instructed to click and drag the mouse to the appropriate position along the line, according to how they felt at that moment. Each scale was scored as an integer from 0 (Definitely not) to 100 (Definitely so), representing the position on the line. |
Countries
Canada
Participant flow
Recruitment details
The period of recruitment was from 29 May 2009 (first subject enrolled) to 01 September 2009 (last subject completed).
Pre-assignment details
A double-blind crossover qualification phase (hydromorphone 8 mg vs. placebo) was followed by a washout period and then randomization to a 5-period, 10-sequence crossover treatment phase. Approximately 40 qualified subjects were to be enrolled in the treatment phase in order to ensure that at least 30 subjects completed all 5 periods of the study.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Randomized to Treatment Phase Forty one (41) qualified subjects were randomized into the treatment phase (Randomized population). Subjects were randomized to 1 of 10 treatment sequences, according to two 5 × 5 Williams squares. Subjects received single oral doses of each of the following 5 treatments, in a randomized, double-blind, crossover manner (1 capsule per treatment period): Placebo, Oxymorphone ER 15 mg, Oxymorphone ER 30 mg, Oxycodone CR 30 mg, and Oxycodone CR 60 mg. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Qualification Phase | Did not meet eligibility criteria | 24 |
| Treatment Phase | Administrative reasons | 2 |
| Treatment Phase | Adverse Event | 2 |
| Treatment Phase | Non-compliance with study restrictions | 1 |
| Treatment Phase | Withdrawn by physician pre-treatment | 1 |
Baseline characteristics
| Characteristic | All Subjects Randomized to Treatment Phase |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants |
| Age, Continuous | 32.4 years STANDARD_DEVIATION 9.04 |
| Region of Enrollment Canada | 41 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 38 | 22 / 37 | 28 / 38 | 35 / 40 | 39 / 40 |
| serious Total, serious adverse events | 0 / 38 | 0 / 37 | 0 / 38 | 0 / 40 | 0 / 40 |
Outcome results
Primary
High VAS - Emax (mm)
The High Visual Analog Scale (VAS) consisted of a horizontal line with a statement presented above the bar (I am feeling high). The ends of the line were marked with the descriptive anchors (Definitely not and Definitely so). Using a laptop computer, participants were instructed to click and drag the mouse to the appropriate position along the line, according to how they felt at that moment. Each scale was scored as an integer from 0 (Definitely not) to 100 (Definitely so), representing the position on the line.
Time frame: High VAS was administered at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Population: Per Protocol population: Subjects who received all 5 treatments and who had no major protocol deviations or other circumstances that would exclude them from the analysis. The pharmacokinetic and pharmacodynamic analyses were performed using the Per Protocol population. No imputation of missing values was performed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High VAS - Emax (mm) | 23.1 mm | Standard Deviation 33.29 |
| Oxymorphone ER 15 mg | High VAS - Emax (mm) | 30.6 mm | Standard Deviation 36.17 |
| Oxymorphone ER 30 mg | High VAS - Emax (mm) | 62.5 mm | Standard Deviation 33.22 |
| Oxycodone CR 30 mg | High VAS - Emax (mm) | 81.4 mm | Standard Deviation 23.17 |
| Oxycodone CR 60 mg | High VAS - Emax (mm) | 93.0 mm | Standard Deviation 12.94 |
p-value: <0.00195% CI: [-41.6, -16]ANCOVA
p-value: <0.00195% CI: [-63.4, -37.5]ANCOVA
p-value: 0.39595% CI: [-7.3, 18.3]ANCOVA
p-value: <0.00195% CI: [25.2, 50.8]ANCOVA
p-value: <0.00195% CI: [43.1, 68.9]ANCOVA
p-value: <0.00195% CI: [53.9, 79.7]ANCOVA