Intranasal ketorolac tromethamine (SPRIX(R)) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: safety and efficacy data from a phase II clinical trial.
OBJECTIVE
Ketorolac is a non-triptan, non-opioid, mixed cyclooxygenase (COX)1/2-inhibitor for short-term management of moderate-to-severe acute pain. This trial evaluated an intranasal formulation of ketorolac tromethamine (SPRIX®) containing 6% lidocaine (ROX-828) for the acute treatment of migraine with and without aura as defined by the International Headache Society.


METHODS
Patients were randomly assigned 1:1 to self-treat with intranasal ROX-828 (31.5 mg ketorolac tromethamine/200 µL, containing 6% of lidocaine) or placebo (with 6% lidocaine) within four hours of a new migraine attack rated ≥ moderate in pain intensity. Assessments included headache intensity and associated migraine symptoms (nausea, vomiting, phonophobia, photophobia) measured at baseline and at regular intervals through 48 hours post-dosing, and global impression of efficacy (seven-point scale) measured at two hours.


RESULTS
Randomized patients who had a migraine attack (N = 140) were evaluable (ROX-828, N = 68; placebo, N = 72). Patients receiving ROX-828 showed a significant (p < 0.05) improvement in pain relief at all time points except 0.5 and 24 hours compared with those who received placebo. More patients achieved pain-free status with ROX-828 than with placebo at 1.5, 3, 4, 24 and 48 hours (p < 0.05); significance at the two-hour time point, which was the primary endpoint, was not met. Patients' global impression of efficacy showed statistically significantly better results for patients receiving ROX-828 than for those receiving placebo. Associated migraine symptoms were significantly improved (p < 0.05) with ROX-828 relative to placebo at several time points throughout the observation period. The most frequently reported adverse events in both groups were associated with nasal discomfort.


CONCLUSIONS
Self-administered intranasal ROX-828 was well tolerated. While the primary endpoint was not met, the results provide preliminary evidence that ROX-828 improves migraine pain.
Neurological Practice, Klenzestrasse 32, Munich 80469, Germany. dr.pfaffenrath@neuro-one.de
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Pfaffenrath
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Fenzl
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Bregman
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Färkkila
D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000009:adverse effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020911:Ketorolac Tromethamine / Q000008:administration & dosage* / Q000009:adverse effects; D008012:Lidocaine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
D000779:Anesthetics, Local; D016861:Cyclooxygenase Inhibitors; D020911:Ketorolac Tromethamine; D008012:Lidocaine