OBJECTIVE: To assess the efficacy and safety of morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA; MS-sNT), which contain morphine sulfate pellets with a sequestered naltrexone core, in treating patients with chronic, moderate-to-severe osteoarthritis (hip or knee) pain. PATIENTS AND METHODS: This phase 3 study had an enriched-enrollment, randomized-withdrawal, double-blind, multicenter design. Patients (N = 547) were titrated to an effective dose of MS-sNT (20-160 mg/day). Responders (n = 344) were randomized to 12 weeks maintenance with an effective MS-sNT dose or were tapered to placebo over 2 weeks. The primary efficacy measure was the change from baseline (CFB) in diary average-pain scores (0-10 scale, Brief Pain Inventory [BPI]) from randomization to the last 7 days of the maintenance period. Secondary efficacy measures included the remaining BPI scores and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. Opioid withdrawal symptoms were assessed by the Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Scale (SOWS). The study ran from January 10, 2007 through November 8, 2007. RESULTS:MS-sNT maintained pain control better than placebo (mean CFB, diary average-pain score, -0.2 +/- 1.9 vs +/-0.3 +/- 2.1; P = 0.045). Change from baseline for MS-sNT pain-diary score (worst, least, average, current) was superior during the maintenance period visits, weeks 2 to 12 (P < 0.05). WOMAC composite score CFB was superior at most visits. MS-sNT was generally well tolerated, with a typical morphine safety profile. No patient taking MS-sNT as directed experienced withdrawal symptoms. CONCLUSION:MS-sNT provided effective analgesia in patients with chronic, moderate-to-severe osteoarthritis pain, with a safety profile typical of morphine-containing products. Naltrexone sequestered in MS-sNT had no clinically relevant effect when MS-sNT was taken as directed.
RCT Entities:
OBJECTIVE: To assess the efficacy and safety of morphine sulfate and naltrexone hydrochloride extended release capsules (EMBEDA; MS-sNT), which contain morphine sulfate pellets with a sequestered naltrexone core, in treating patients with chronic, moderate-to-severe osteoarthritis (hip or knee) pain. PATIENTS AND METHODS: This phase 3 study had an enriched-enrollment, randomized-withdrawal, double-blind, multicenter design. Patients (N = 547) were titrated to an effective dose of MS-sNT (20-160 mg/day). Responders (n = 344) were randomized to 12 weeks maintenance with an effective MS-sNT dose or were tapered to placebo over 2 weeks. The primary efficacy measure was the change from baseline (CFB) in diary average-pain scores (0-10 scale, Brief Pain Inventory [BPI]) from randomization to the last 7 days of the maintenance period. Secondary efficacy measures included the remaining BPI scores and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. Opioid withdrawal symptoms were assessed by the Clinical Opiate Withdrawal Scale (COWS) and Subjective Opiate Withdrawal Scale (SOWS). The study ran from January 10, 2007 through November 8, 2007. RESULTS: MS-sNT maintained pain control better than placebo (mean CFB, diary average-pain score, -0.2 +/- 1.9 vs +/-0.3 +/- 2.1; P = 0.045). Change from baseline for MS-sNTpain-diary score (worst, least, average, current) was superior during the maintenance period visits, weeks 2 to 12 (P < 0.05). WOMAC composite score CFB was superior at most visits. MS-sNT was generally well tolerated, with a typical morphine safety profile. No patient taking MS-sNT as directed experienced withdrawal symptoms. CONCLUSION: MS-sNT provided effective analgesia in patients with chronic, moderate-to-severe osteoarthritis pain, with a safety profile typical of morphine-containing products. Naltrexone sequestered in MS-sNT had no clinically relevant effect when MS-sNT was taken as directed.
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