Investigation of topical intranasal cocaine for sinonasal procedures: a randomized, phase III clinical trial.

BACKGROUND

The objective of this trial was to demonstrate the clinical efficacy and safety of topical cocaine as part of the effort to gain regulatory approval from the United States Food and Drug Administration.

METHODS

This phase III, randomized, prospective, double-blind, multicenter, single-dose, placebo- and dose-controlled, parallel-group study aimed to evaluate the safety and efficacy of topical intranasal cocaine (RX0041-002). A total of 925 subjects were screened and a total of 648 subjects were randomized: 95 to placebo; 275 to 4% RX0041-002; and 278 to 8% RX0041-002. Efficacy was assessed with subjective pain intensity scores using the visual numeric rating scale and objectively using the von Frey filament test. Adverse events (AEs), vital signs, Holter monitoring, nasal irritation on visual examination, and smell assessment were recorded. The placebo and experimental groups were compared using a two-tailed Fisher's exact test.

RESULTS

Topical 4% and 8% cocaine achieved significant subject analgesia, the primary efficacy endpoint. Both doses were safe and well-tolerated, with a safety profile similar to placebo. In the 4% and 8% groups, headache (1.5% and 2.5%, respectively), epistaxis (0.7% and 1.1%), and anxiety (0.7% and 0%) were the only AEs reported by >1 subject. No cardiovascular AEs, serious AEs, or deaths occurred. A higher percentage of subjects in the 4% and 8% groups compared with the placebo group had a modest increase in either systolic or diastolic blood pressure.

CONCLUSION

Topical 4% and 8% cocaine is an effective anesthetic that can be safely administered for nasal procedures.