Positive Pharmacokinetic Study Results Of Investigational Abuse-Deterrent, Extended-Release Opioid
Investigational Abuse-Deterrent, Extended-Release Opioid
Alpharma presented positive results of a pharmacokinetic study of its investigational abuse-deterrent, extended-release opioid at the 26th annual scientific meeting of the American Pain Society in Washington.
The data demonstrated the release characteristics of this extended-release morphine sulfate plus sequestered naltrexone product were similar to that found in previous studies of Alpharma's currently marketed KADIAN (morphine sulfate extended-release) Capsules.
"There is a clear need for new medications that provide pain relief while deterring abuse and we believe our technology may offer a significant abuse- deterrent option for physicians treating patients suffering from moderate-to- severe chronic pain," says Joseph Stauffer, DO, Chief Medical Officer Clinical Research & Medical Affairs and Senior Vice President, Alpharma Pharmaceuticals LLC. "We are committed to offering physicians the tools needed to treat patients with moderate-to-severe chronic pain."
Alpharma's proprietary technology combines an extended-release opioid with a sequestered core of the antagonist, naltrexone. If the product is taken as directed, it is intended that the naltrexone will remain sequestered and the patient will achieve pain relief similar to KADIAN (morphine sulfate extended-release) Capsules. If the capsule is tampered with by crushing, chewing or dissolving, it is designed so that the naltrexone will be released and euphoria will be abated.
In the single-dose, open-label, two-period crossover study (fasted and fed) in eight healthy subjects, 21 to 45 years of age, after an overnight fast, subjects either received the study drug (containing 60 mg morphine sulfate) or consumed a standard high-calorie, high-fat breakfast and took the study drug 30 minutes later. Blood samples for morphine pharmacokinetic analysis were drawn prior to dosing and at intervals from 0.5 to 168.0 hours post-dose.
The results of the pharmacokinetic analysis demonstrated, for both the fasted and fed states that the release characteristics of morphine were consistent with a sustained-release formulation and were similar to previous study results for KADIAN (morphine sulfate extended-release) Capsules. Most naltrexone levels were below the assay measurement limits. Adverse events, reported in five subjects, were mild to moderate in intensity and resolved without treatment.
This study was conducted as part of Alpharma's medical development program for its abuse-deterrent morphine product, and its results were consistent with data generated in the Phase II clinical program for this product.. The company is targeting an NDA filing for its abuse-deterrent product in the first half of 2008.
Also presented at the annual meeting were data that showed the extended- release properties of KADIAN were maintained even in the presence of a significant quantity of alcohol. These results indicate that the concomitant use of tested levels of alcohol with KADIAN has no significant impact on mean morphine blood levels or the timing of morphine release. Recently, the U.S. Food and Drug Administration completed a review of this data and concluded that the KADIAN black box warning did not need to include any precautionary language related to alcohol.
KADIAN capsules are an extended-release oral formulation of morphine sulfate indicated for the management of moderate-to-severe pain, when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. The capsules can be taken once-daily (q24h) or twice-daily (q12h), as prescribed, to provide up to 24 hours of pain relief. KADIAN capsules are not for use as a prn analgesic.
KADIAN capsules are available in eight strengths: 10 mg, 20 mg, 30 mg, 50 mg, 60 mg, 80 mg, 100 mg and 200 mg. The 100 mg and 200 mg capsules are for use in opioid-tolerant patients only. KADIAN offers flexible dosing and administration options that allow physicians to fine-tune titration schedules and tailor treatment for individual patient needs.
KADIAN capsules may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension and profound sedation or coma may result.
KADIAN side effects are generally consistent with those found with other opioids. The most common include drowsiness, constipation, nausea, dizziness and anxiety. Serious adverse reactions that may be associated with KADIAN include respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, low blood pressure and/or shock.
KADIAN capsules contain an opioid agonist which is a Schedule II controlled substance. KADIAN has an abuse liability similar to other opioids. This should be considered when prescribing or dispensing KADIAN.