Bridgewater, N.J., October 15, 2007– Alpharma Pharmaceuticals LLC, a subsidiary of Alpharma Inc.(NYSE: ALO), a leading global specialty pharmaceutical company, presented results from a Phase 2 study that showed ALO-01, an extended-release morphine sulfate plus sequestered naltrexone, provided similar effectiveness to KADIAN® (morphine sulfate extended-release) Capsules in osteoarthritis patients with moderate-to-severe chronic pain. The data were presented at the annual meeting of the American Society of Anesthesiologists in San Francisco, Calif., on October 15, 2007.
Results showed:
- ALO-01 showed similar effectiveness to KADIAN® and maintained pain reduction throughout the study.
- The sequestered naltrexone did not interfere with patients’ pain relief.
- The majority of patients rated both medications as good, very good or excellent.
“We are pleased with the results of this Phase 2 trial with ALO-01, which showed our investigational abuse-deterrent product provides similar pain relief and tolerability as our extended-release opioid KADIAN®,” commented Joseph Stauffer, DO, Chief Medical Officer, Senior Vice President of Clinical Research & Medical Affairs, Alpharma Pharmaceuticals LLC. “Based on these positive findings, we began Phase 3 trials for ALO-01, which have been fully enrolled, reinforcing our commitment to providing relief to patients with moderate-to-severe chronic pain while helping to reduce the risk of misuse, abuse and diversion.”
ALO-01, formerly referred to as KADIAN® NT, is being studied under an investigational new drug application for moderate-to-severe chronic pain. The product is developed with Alpharma’s proprietary technology, which combines an extended-release opioid with sequestered naltrexone, an opioid antagonist. When ALO-01 is taken as directed, it provides pain relief and the naltrexone remains sequestered in the pellet core and passes though the gastrointestinal tract without significant absorption. If the product is crushed, chewed or dissolved, the naltrexone is released and designed to block opioid effects (e.g., euphoria).
“These findings show that when patients take ALO-01 as directed, patients achieve measurable relief of their chronic pain and the naltrexone passes through the body without significant absorption,” says Nathaniel Katz, MD, MS, Assistant Professor of Anesthesia, Tufts University School of Medicine, Boston, Mass., founder of Analgesic Research, and study author.
Study Design
The Phase 2, double-blind, crossover study assessed effectiveness, tolerability and pharmacokinetics of ALO-01 compared with KADIAN® at nine sites in the U.S. In the study, 69 adult patients with moderate-to-severe pain due to osteoarthritis, after a washout from previous treatments, were administered five periods of treatment with study drugs.
- Period One: All patients titrated to effective analgesia with KADIAN®;
- Period Two: Randomized to double-blind treatment with either KADIAN® or ALO-01 for 14 days;
- Period Three: All patients treated with KADIAN® open label for 7 days;
- Period Four: Crossed over to the other study medication, either KADIAN® or ALO-01, for 14 days, depending on randomization in period two;
- Period Five: All patients again treated with KADIAN® open label for 7 days.
Once titrated in period one, the morphine dose was held constant at the stabilized dose during periods two through five.
Study Results
After washout, the mean pain intensity was 7.1 ± 1.5. The mean pain score was reduced to 2.1 ± 1.0 by the end of the titration period. Brief Pain Inventory scores – average pain each day rated on a 0 to 10 scale (least to worst pain) – ¬ were KADIAN®, 2.3; ALO-01, 2.4 on treatment day seven and KADIAN®, 2.4; ALO-01, 2.3 on treatment day 14. Most patients rated both medications as good, very good or excellent, (KADIAN®, 78.9%; ALO-01, 91.5%), according to the Patient Global Assessment of the medication.
During each crossover period, patients’ blood levels were taken and assessed for naltrexone. In most patients the amount of naltrexone was below the level of quantification. In the few patients in which low levels of naltrexone were present, it did not affect the patients’ pain scores or produce symptoms associated with opioid withdrawal.
Adverse events were generally mild to moderate. The most common adverse events during the double-blind treatment period for KADIAN® and ALO-01 were constipation (12.7%; 15.5%), nausea (8.5%; 9.9%) and somnolence/drowsiness (8.5%; 9.9%), respectively.
About KADIAN® Capsules
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®.
For complete prescribing information, visit www.KADIAN.com or call 877-4KADIAN.
About Alpharma
Alpharma Inc. (NYSE: ALO) is a global specialty pharmaceutical company with leadership positions in products for humans and animals. Alpharma is presently active in more than 60 countries. Alpharma has a growing branded pharmaceutical franchise in the U.S. pain market with its KADIAN® (morphine sulfate extended-release) Capsules, and an innovative pharmaceutical product pipeline that consists of several novel approaches to treat pain, including the Flector® Patch (diclofenac epolamine topical patch),which is expected to launch in early 2008. In addition, Alpharma is among the world's leading producers of several specialty pharmaceutical-grade bulk antibiotics and is internationally recognized as a leading provider of pharmaceutical products for poultry and livestock.
KADIAN® is a registered trademark of Alpharma Pharmaceuticals LLC.
Flector® Patch is a registered trademark of Institut Biochemique S.A.