Nocturia has been associated with significant morbidity, negative economic implications and decreased quality of life in those who suffer from it, yet there is currently no universally accepted treatment strategy for its management. A potential therapeutic target in the treatment of nocturia is the prostaglandin (PG) pathway, as PGs have been shown to play a role in modulating detrusor muscle tone and micturition. Thus, the purpose of our study is to assess the safety and efficacy of Paxerol®, a novel immediate:sustained (50%:50%) release formulation of the combination of PG inhibitors, acetaminophen and ibuprofen, at different doses in the management of patients with nocturia.

We identified patients with nocturia without an underlying urinary tract infection, elevated post-void residual, sleep disorder, neurologic disorder or serious medical morbidity treated at multiple clinical sites from March 2016 through September 2017. A two-week, stratified (by gender, BMI, and age), four-arm, double-blind study comparing placebo to low, medium, and high doses of Paxerol® was conducted. Primary outcomes measured were average number of nocturnal voids (ANV) and nocturia quality of life scores (NQOL). Secondary outcome measures were duration of first uninterrupted sleep (DFUS), total hours of nightly sleep (THNS) and safety/tolerability. Differences between the treatment groups were compared using analysis of variance.

A total of 133 patients were screened, in which 86 were eligible and enrolled in the study. The full study protocol was completed by 80 patients (all 86 patients analyzed by intention to treat). There were no significant differences in the demographic and baseline voiding characteristics of study subjects amongst the four groups. We found a significantly greater decrease in ANV in patients treated with Paxerol® at all 3 doses as compared to placebo. There was a decrease in overall NQOL scores in all groups, with a significantly larger reduction in the medium and high dose Paxerol® groups compared to placebo. We found an increase in DFUS in all four groups, with a significantly larger increase in the high dose Paxerol® group compared to placebo. There was no significant difference in the THNS in the Paxerol® groups compared to placebo. There were no severe adverse events and none of the adverse events were believed to have been related to the study drug.

The significant decrease in ANV in each of the Paxerol® groups, combined with the significant improvement in NQOL scores in the medium and high dose Paxerol® groups compared to placebo, suggests that the effects in the medium and high dose groups has a positive subjective impact in patient’s perception of their voiding symptoms. In addition, the observation that high dose Paxerol® demonstrated a significant increase in DFUS compared to placebo with no associated change in THNS suggests that patients found an improvement in their quality of sleep without a change in total duration of sleep. Our study was limited by its small sample size, lack of full bladder diary parameters analysis and short duration of therapy.

This Phase 2 trial demonstrated short-term safety and efficacy of Paxerol® for the treatment of nocturia symptoms compared to placebo. Further long term clinical studies are warranted to validate these findings.