A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: NCCTG study N04CA.

9024 Background: Vaginal dryness is a common problem, for which effective and safe non-estrogenic treatments are needed. Based on preliminary promising data that pilocarpine attenuated vaginal dryness (Arch Intern Med 159:174-81, 1999), the current trial was conducted. Methods: A double-blind, placebo (PLCB)-controlled, randomized trial design was used to compare pilocarpine, at target doses of 5 mg twice daily and 5 mg four times daily, to a PLCB. Patients (pts) must have had persistent vaginal dryness and/or itching of sufficient severity to desire therapeutic intervention. Vaginal dryness was recorded by pt-completed questionnaires at baseline and weekly for 6 weeks. The primary endpoint was the area under the curve (AUC) summary statistic comprised of the longitudinal responses obtained at baseline and through the 6 weeks of treatment to a 0-10 numerical analogue scale, asking pts to rate their perceived amount of vaginal dryness. The primary analysis was carried out by a single t-test using a two-sided alternative and 5% Type I error to compare the collective pilocarpine treatment arms versus the collective PLCB arms. The two-sample t-test for the primary analysis, with 128 pts in the pilocarpine arms and 64 pts in the PLCB arm, had 80% power to detect a difference of 50% times the standard deviation. Results: 201 pts (195 evaluable) were enrolled in this trial; 64, 65, and 66 pts in the PLCB, lower dose pilocarpine and higher dose pilocarpine treatment arms. The primary analysis, comparing vaginal dryness symptoms, did not reveal any benefit for the collective pilocarpine arms or either of the individual pilocarpine treatment arms, all compared to the PLCB arm, with each group improving from about 42/100 to about 72/100 (all p>0.424). At the end of the study, 27 (54%), 27 (50%), and 31 (53%) of the pts stated that they had improvements in vaginal dryness in the PLCB, lower dose pilocarpine, and higher dose pilocarpine treatment arms (p = 0.132). Toxicity evaluation revealed more rigors (p = 0.002), urinary frequency (p = 0.006), nausea (p = 0.030), and sweating (p = 0.062) in the pilocarpine arms, compared to the PLCB arm. Conclusions: Pilocarpine did not alleviate vaginal dryness, yet did cause some toxicity. No significant financial relationships to disclose.