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ANALGESIA

The Analgesic Efficacy and Safety of a Novel Intranasal Morphine Formulation (Morphine plus Chitosan), Immediate Release Oral Morphine, Intravenous Morphine, and Placebo in a Postsurgical Dental Pain Model

Kyle S. Christensen, DDS^*, Amy E. Cohen, MS, Fred H. Mermelstein, PhD, Douglas A. Hamilton, MBA, Ewan McNicol, MS^||, Najib Babul, PharmD^¶, and Daniel B. Carr, MD^#

From the *Jean Brown Associates, Salt Lake City, Utah; Clinical Operations, Javelin Pharmaceuticals, Cambridge, Massachusetts; New Biology Ventures, San Francisco, California; ||Analgesic Trial Design, Charlestown, Massachusetts; ¶TheraQuest Biosciences Inc., Blue Bell, Pennsylvania; and #Tufts Medical Center, Boston, Massachusetts.

Address correspondence and reprint requests to Dr. Daniel B. Carr, Javelin Pharmaceuticals, 125 Cambridge Park Dr., Cambridge, MA 02140. Address e-mail to dcarr{at}javelinpharma.com.

Abstract

BACKGROUND: Opioids are standard treatment for postoperative pain. In this study, we compared the safety and efficacy of intranasal (IN) morphine to IV and oral morphine and placebo.

METHODS: Two-hundred-twenty-five patients with moderate-to-severe pain after third molar extraction were randomized to receive a single dose of IN morphine 7.5 mg or 15 mg, IV morphine 7.5 mg, oral morphine 60 mg or placebo. Pain intensity was assessed using visual analog and categorical scales, and pain relief using a categorical scale. Outcomes included total pain relief, pain intensity difference, summed pain intensity difference, time to analgesic onset, time to requesting rescue medication, and patients’ global evaluation of their treatment. Safety assessments included adverse event recording and nasal examinations.

RESULTS: Across the various efficacy outcomes, both IN morphine doses were statistically similar to the positive comparators (IV and oral morphine), and all four morphine treatments were statistically superior to placebo. Overall, IN morphine 15 mg presented an efficacy profile similar to IV morphine 7.5 mg; both treatments demonstrated rapid onset of efficacy, generally persistent throughout the 6-h assessment period. The lower dose of IN morphine, 7.5 mg, was statistically similar to the other active treatments at 2 h and 6 h and similar to placebo at 4 h. Study medications were generally well tolerated, with no withdrawals due to adverse events or other safety concerns, and no serious adverse events reported. The most frequently reported adverse events were typical systemic opioid effects.

CONCLUSIONS: IN morphine offers a noninvasive alternative to IV morphine for postoperative analgesia.