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

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

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.

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.

Inclusion Criteria:

1. Man or woman, 18-65 years of age, inclusive
2. Able to provide informed consent and comply with all study procedures
3. Women of childbearing potential with a negative urine pregnancy test at screening and on adequate contraception
4. Chronic, non-malignant, painful condition, treated with long-acting opioid (methadone, OxyContin®, MS (Morphine Sulfate) Contin®, Kadian®, Avinza®, Fentanyl®, Opana® ER)
5. 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
6. 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
7. Weight at screening 100-300 pounds, inclusive

Exclusion Criteria:

1. Pregnant or breastfeeding
2. Gastrointestinal disorder or S/P gastrointestinal surgery impacting absorption of study medication (delayed gastric emptying, partial or complete gastrectomy)
3. Alcohol or substance abuse within 2 years of screening
4. Consumption of alcohol within 24 hours of a screening or testing visit
5. Consumption of xanthine-containing beverages (coffee, tea, coke) on the morning of a screening or testing visit
6. Impaired kidney or liver function (transaminase levels more than 3 times elevated; estimated creatinine clearance less than 50 mL/min)
7. Epworth sleepiness scale (ESS) score 16 or higher at screening
8. Medically concerning hypertension (≥ 160/100) or unstable cardiovascular illness
9. Any clinically significant illness that would interfere with study participation or put the subject at risk
10. Exposure to investigational medication within 30 days of screening