Effect of Extended-release Oxymorphone Taken With or Without Food on Cognitive Functioning

Study Overview
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Brief Summary
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The purpose of the study is to determine whether extended-release oxymorphone hydrochloride taken orally with a high-fat meal, generating an approximately 50% higher Cmax, impacts cognitive functioning, using Cambridge Neuropsychological Test Automated Battery (CANTAB) tests, to a greater extent than when taking under conditions of fasting.

Detailed Description
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Oxymorphone 40 mg ER affects cognitive performance similarly within 3 hours post dose, whether given on an empty stomach or after a high-fat meal, suggesting that the altered pharmacokinetics, fed versus fasting and as described above, is not relevant for the medication's impact on cognition. Hence, the direction for oxymorphone ER to be dosed at least 1 hour before or 2 hours after eating, at least from a cognitive perspective, may be without merit.

Official Title
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Effect of Extended-release Oxymorphone Hydrochloride (Opana® ER), Taken Fasting Versus With Food, on Cognitive Functioning in Opioid-tolerant Subjects: a Randomized, Single-blinded, Cross-over Study

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: Oxymorphone ER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man or woman, 18-65 years of age, inclusive Able to provide informed consent and comply with all study procedures Women of childbearing potential with a negative urine pregnancy test at screening and on adequate contraception Chronic, non-malignant, painful condition, treated with long-acting opioid (methadone, OxyContin®, MS (Morphine Sulfate) Contin®, Kadian®, Avinza®, Fentanyl®, Opana® ER) Opioid treatment for at least 3 months prior to screening at a minimum dose of 90 mg of morphine equivalents per day or 50 mcg of the fentanyl transdermal patch Dose of opioid treatment stable for at least 1 week prior to screening and expected to be stable from screening through end of second testing Weight at screening 100-300 pounds, inclusive Exclusion Criteria: Pregnant or breastfeeding Gastrointestinal disorder or S/P gastrointestinal surgery impacting absorption of study medication (delayed gastric emptying, partial or complete gastrectomy) Alcohol or substance abuse within 2 years of screening Consumption of alcohol within 24 hours of a screening or testing visit Consumption of xanthine-containing beverages (coffee, tea, coke) on the morning of a screening or testing visit Impaired kidney or liver function (transaminase levels more than 3 times elevated; estimated creatinine clearance less than 50 mL/min) Epworth sleepiness scale (ESS) score 16 or higher at screening Medically concerning hypertension (≥ 160/100) or unstable cardiovascular illness Any clinically significant illness that would interfere with study participation or put the subject at risk Exposure to investigational medication within 30 days of screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxymorphone ER 40 mg fed<br>Participants received 40 mg oxymorphone ER after a high-fat meal of approximately 1,010 kCal | Drug: Oxymorphone ER<br>* 40 mg qd twice<br>* Other names: Opana ER;|
| Experimental: Oxymorphone ER 40 mg fasting<br>Participants received 40 mg oxymorphone ER after fasting for 8-12 hours | Drug: Oxymorphone ER<br>* 40 mg qd twice<br>* Other names: Opana ER;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rapid Visual Information Processing (RVP) Sensitivity [A'] | RVP is a test of sustained attention. It is a sensitive measure of general cognitive performance. A white box appears in the center of the computer screen, inside which digits, from 2 to 9, appear in a pseudorandom order, at the rate of 100 digits per minute. The subject is requested to detect target sequences of three digits (for example, 2-4-6, 3-5-7, 4-6-8) and to register responses using the response box. The two main outcome measures are the probability to detect the predefined sequence (sensitivity [A']) and the speed at which the sequence is registered (response latency [ms]). | 1 and 3 hours postdose | 
| Rapid Visual Information Processing (RVP) Response Latency | RVP is a test of sustained attention. It is a sensitive measure of general cognitive performance. A white box appears in the center of the computer screen, inside which digits, from 2 to 9, appear in a pseudorandom order, at the rate of 100 digits per minute. The subject is requested to detect target sequences of three digits (for example, 2-4-6, 3-5-7, 4-6-8) and to register responses using the response box. The two main outcome measures are the probability to detect the predefined sequence (sensitivity [A']) and the speed at which the sequence is registered (response latency [ms]). | 1 and 3 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spatial Recognition Memory (SRM) Test Percentage of Correct Hits | SRM tests visual spatial recognition memory in a two-choice forced discrimination paradigm. The subject is presented with a white square, which appears in sequence at five different locations on the screen. In the recognition phase, the subject sees a series of five pairs of squares, one of which is in a place previously seen in the presentation phase. The other square is in a location not seen in the presentation phase. Locations are tested in the reverse of the presentation order. The two main outcome measures are the percentage of correct trials (correct hits [%]) and the speed of the subject's response (response latency [ms]). | 1 and 3 hours postdose | 
| Spatial Recognition Memory (SRM) Test Response Latency | SRM tests visual spatial recognition memory in a two-choice forced discrimination paradigm. The subject is presented with a white square, which appears in sequence at five different locations on the screen. In the recognition phase, the subject sees a series of five pairs of squares, one of which is in a place previously seen in the presentation phase. The other square is in a location not seen in the presentation phase. Locations are tested in the reverse of the presentation order. The two main outcome measures are the percentage of correct trials (correct hits [%]) and the speed of the subject's response (response latency [ms]). | 1 and 3 hours postdose | 
| Spatial Working Memory (SWM) Test Total Errors | SWM is a test of the subject's ability to retain spatial information and to manipulate remembered items in working memory. It is a self-ordered task, which also assesses heuristic strategy. The test is a sensitive measure of executive function. It begins with a number of colored squares (boxes) being shown on the screen. By touching the boxes and using a process of elimination, the subject finds blue tokens in a number of boxes and uses them to fill up an empty column on the screen. The number of boxes is gradually increased, until it is necessary to search a total of eight boxes. The color and position of the boxes are changed from trial to trial to discourage the use of stereotyped search strategies. The two main outcome measures are errors (touching boxes that have been found to be empty and revisiting boxes that have already been found to contain a token - total errors) and a measure of strategy (strategy score). | 1 and 3 hours postdose | 
| Spatial Working Memory (SWM) Test Strategy Score | SWM is a test of the subject's ability to retain spatial information and to manipulate remembered items in working memory. The test is a sensitive measure of executive function. It begins with a number of colored squares (boxes) being shown on the screen. By touching the boxes and using a process of elimination, the subject finds blue tokens in a number of boxes and uses them to fill up an empty column on the screen. The number of boxes is gradually increased, until it is necessary to search a total of eight boxes. The color and position of the boxes are changed from trial to trial to discourage the use of stereotyped search strategies. The two main outcome measures are errors (touching boxes that have been found to be empty and revisiting boxes that have already been found to contain a token - total errors) and a measure of strategy (For assessed problems with six boxes or more, the number of distinct boxes used by the subject to begin a new search for a token) | 1 and 3 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid tolerant, chronic pain