Monday August 19, 6:36 pm Eastern Time
Press Release
SOURCE: Ligand Pharmaceuticals Incorporated
Long-Term Study Presented at IASP Demonstrates AVINZA Once-Daily Provides Stable Analgesia for One Year Without Increase in Use of Rescue Medicines
Second Study Shows that AVINZA Improves Physical Functioning
SAN DIEGO--(BW HealthWire)--Aug. 19, 2002-- Ligand's new once-daily pain product, AVINZA(TM) (morphine sulfate extended-release capsules), provided stable analgesia for one year without an increase in the use of rescue medicines, according to a long-term clinical study presented at the 10th World Congress of the International Association for the Study of Pain.
In a second study presented at the meeting, AVINZA improved physical functioning, one aspect of quality of life, in patients with chronic, moderate-to-severe osteoarthritis pain who completed up to 30 weeks of treatment.
Once-daily AVINZA was approved in March by the U.S. Food and Drug Administration for the relief of moderate-to-severe pain in patients requiring continuous, around-the-clock opioid therapy for an extended period of time. Ligand launched the product into the $2.3 billion sustained-release opioid market in June of this year.
In the first study, Dr. Daniel Wynn, Dr. Richard Rauck and colleagues evaluated the long-term safety and efficacy of AVINZA in 284 patients with chronic, moderate-to-severe pain of malignant and non-malignant origin. Patients who completed one of four previous AVINZA studies were included in the one-year, open-label trial, and were evaluated monthly for safety and efficacy. Dose changes of AVINZA, rescue medicines (drugs such as NSAIDs and short-acting opioids that are used to relieve breakthrough pain) and concomitant medicines were allowed. 137 patients completed the trial. The median daily dose of AVINZA was 120 mg at baseline, 180 mg at six months, and remained stable from six to 12 months.
"There were no statistically significant or clinically meaningful changes in pain intensity during the one-year study, indicating that AVINZA provided stable, long-term analgesia," said Dr. Rauck, from Piedmont Anesthesia and Pain Consultants in Winston-Salem, NC. "In addition, there were no statistically significant changes in the number of daily rescue medicines required from baseline to one year. After baseline, the mean number of daily rescue medicines required was only two, indicating that AVINZA was able to control pain with once-daily dosing."
In the study, side effects were similar to those typically observed with opioid therapy, and most were of mild to moderate severity. The most common treatment-related side effects were nausea (20% of the 284 patients), constipation (19%) and vomiting (13%). Sixty-four patients (23%) experienced 138 serious adverse events, two of which were considered probably or definitely treatment-related. Fourteen deaths (5%), none of which were treatment-related, occurred due to disease progression.
In the second study, Dr. Sanford Roth and colleagues evaluated physical functioning in nearly 300 patients who took AVINZA for up to 30 weeks. The study included a four-week double-blind portion, in which the safety and efficacy of AVINZA 30 mg were compared to a placebo and to MS Contin (MSC, morphine sulfate controlled-release, Purdue Frederick), and an additional 26-week, open-label extension study of AVINZA given once-daily in the morning (QAM) or evening (QPM). Patients' dose could be increased in the open-label extension study, but not during the four-week double-blind portion. 184 of 295 patients completed the four-week controlled study, and 86 of 181 patients completed the open-label extension. Safety and analgesic efficacy results were previously published in the Journal of Pain and Symptom Management (2002; 23; 278-291). Physical functioning, an aspect of quality of life, was measured weekly during the four-week double-blind portion of the study, and at weeks five, eight, 12, 18, 24 and 30 during the open-label extension.
"AVINZA had a positive effect on physical functioning in osteoarthritis patients who completed up to 30 weeks of treatment, and was statistically superior to MS Contin on some occasions," said Dr. Roth, of ArthroCare in Phoenix.
Physical functioning was measured using two methods, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the SF-36 Physical Functioning Summary Score. The WOMAC physical functioning scale includes 17 questions, each of which is scored from 0 to 100, that reflect a patient's ability to perform daily activities such as walking, standing and sitting. The SF-36 Physical Functioning Summary Score is calculated from subscores on bodily pain, physical role, physical functioning and general health, each of which is scored from 0 to 100.
In the four-week study based on WOMAC results, statistically significant (p less than .05) improvements in physical functioning compared to placebo were observed at all four of the weekly visits for patients taking the AVINZA QAM dose, and at three of the weekly visits for patients taking the AVINZA QPM dose. In contrast, for MSC, significant improvements compared to placebo were observed only at the first weekly visit. Based on SF-36 results, significant improvements in physical functioning compared to placebo were observed at three of the weekly visits for patients taking the AVINZA QAM dose, and at all four of the weekly visits for patients taking the AVINZA QPM dose. In addition, physical functioning was significantly improved versus MSC at week four for patients taking the AVINZA QAM dose, and at weeks two and four for patients taking the AVINZA QPM dose.
In the open-label study of AVINZA, statistically significant improvements in physical functioning compared to baseline were observed at every evaluation point in weeks five through 30, based on both WOMAC and SF-36 results.
"The WOMAC improvements in physical functioning through week 12 (week eight of the open-label study) corresponded with an increase in the mean daily AVINZA dose, indicating that the ability to titrate led to improved performance," Dr. Roth said. "After week 12, physical functioning was stable, as was the average daily dose of AVINZA, indicating that optimal risk/benefit balance was achieved. Even with the ability to increase dose, the mean once-daily dose of AVINZA at the end of the study was 50 mg, a modest amount of sustained-release morphine."
In the study, side effects were similar to those typically observed with opioid therapy, most commonly constipation and nausea. |
