Civamide cream 0.075% in patients with osteoarthritis of the knee: a 12-week randomized controlled clinical trial with a longterm extension.

OBJECTIVE: To evaluate the safety and efficacy of civamide cream 0.075% for the treatment of osteoarthritis (OA) of the knee. METHODS: We conducted a 12-week, multicenter, randomized, double-blind study with a 52-week open-label extension. Patients with OA of the knee received either civamide cream 0.075% or a lower dose of civamide cream, 0.01%, as the control. The 3 co-primary endpoints in the double-blind study were the time-weighted average (TWA) of change from baseline to Day 84 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, the WOMAC physical function subscale, and the Subject Global Evaluation (SGE). In the 52-week open-label extension study, the Osteoarthritis Pain Score and SGE were assessed. RESULTS: A total of 695 patients were randomized to receive civamide cream 0.075% (n = 351) or civamide cream 0.01% (control; n = 344) in the double-blind study. Significance in favor of civamide cream 0.075% was achieved for the TWA for all 3 co-primary efficacy variables: WOMAC pain (p = 0.009), WOMAC physical function (p < 0.001), and SGE (p = 0.008); and at Day 84 for these 3 variables (p = 0.013, p < 0.001, and p = 0.049, respectively). These analyses accounted for significant baseline-by-treatment interactions. In the 52-week open-label extension, efficacy was maintained. Civamide cream 0.075% was well tolerated throughout the studies. CONCLUSION: These studies demonstrate the efficacy of civamide cream for up to 1 year of continuous use. Civamide cream, with its lack of systemic absorption, does not have the potential for serious systemic toxicity, in contrast to several other OA treatments.

Intranasal civamide for the treatment of episodic cluster headaches.

OBJECTIVE: To evaluate the safety and efficacy of intranasal civamide solution for preventive treatment during an episodic cluster headache period. SUBJECTS AND METHODS: This was a multicenter, double-blind, randomized, vehicle-controlled study with a 7-day treatment period and a 20-day posttreatment period performed at 14 headache/neurology centers in the United States. Twenty-eight subjects were randomized to receive civamide or its vehicle in a 2:1 ratio; 18 received civamide and 10 received the vehicle. Subjects received 100 microL of 0.025% civamide (25 microg) or 100 microL of the vehicle to each nostril via dropper once daily for 7 days. The total daily dose of civamide was 50 microg. MAIN OUTCOME MEASURES: The number of cluster headaches per week during the treatment and posttreatment periods, pain intensity, presence of associated symptoms, and the incidence of adverse events were assessed. RESULTS: Subjects in the civamide group had a significantly greater percent decrease in the number of headaches from baseline to posttreatment during days 1 through 7 (-55.5% vs -25.9%; P =.03) and a trend toward significance during days 8 through 14 (-66.9% vs -32.3%; P =.07) and days 15 through 20 (-70.6% vs -34.9%; P =.07), as well as a near-significant decrease during the entire posttreatment period (days 1 through 20 [P =.054]) compared with the vehicle group. There were larger decreases in the number of headaches per week during the posttreatment period in the civamide-treated group, with trends toward significance during posttreatment days 8 through 14 (-8.6 vs -3.6; P =.09) and days 15 through 20 (-8.9 vs -3.6; P =.07). There were no significant differences between groups in cluster headache pain intensity, number of severe headaches, or associated symptoms. The most common adverse events included nasal burning (14 of 18 civamide-treated subjects, 1 of 10 vehicle-treated subjects; P =.001) and lacrimation (9 of 18 civamide-treated subjects, 0 of 10 vehicle-treated subjects; P =.01). CONCLUSION: Intranasal civamide solution at a dose of 50 microg may be modestly effective in the preventive treatment of episodic cluster headache.