Novel Prolonged Action Formulation of Acetaminophen-Ibuprofen Combination (Paxerol®) Therapy for Treatment of Nocturia: A Multi-Center, Randomized, Double Blinded, Placebo-Controlled, 4-Arm Phase 2 Trial

Kashan M1, Khusid J A1, Weiss J P1, Rauscher F2, Blair B3, Efros M4, Kaminesky J5, Contreras J6, Rydin I7, Xie L8, Whisnant J8, Lee K9

Research Type


Abstract Category


Abstract 8
Scientific Podium Short Oral Session 2
Wednesday 29th August 2018
08:42 - 08:50
Hall B
Clinical Trial Nocturia Pharmacology
1. Downstate College of Medicine, Department of Urology, 450 Clarkson Avenue, Brooklyn, NY 11203, 2. WISTAR Institute, Department of Gene Expression and Regulation, 3601 Spruce Street, Philadelphia, PA 19104, 3. WESTMED Medical Group, 210 Westchester Avenue, White Plains, NY 10604, 4. AccuMed Research Associates, 1305 Franklin Avenue, Garden City, NY 11530, 5. Manhattan Medical Research, 215 Lexington Avenue, 21th Floor, NY, NY 10016, 6. Washington Heights Urology, 286 Fort Washington Ave, NY, NY 10032, 7. A and I Medical PC, 1773 E 19 Street, Suite 1C, Brooklyn, NY 11229, 8. Brightech International, LLC., 285 Davidson Ave, Suite 504, Somerset, NJ 08873, 9. Quinnipiac University, 275 Mount Carmel Avenue, Hamden, CT 06518; Axella Research, 2330 Eastchester Road, Bronx, NY 10469

Mahyar Kashan



Hypothesis / aims of study
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.
Study design, materials and methods
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.
Interpretation of results
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.
Concluding message
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.
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<span class="text-strong">Funding</span> This study was supported and sponsored by Wellesley Pharmaceuticals, LLC. <span class="text-strong">Clinical Trial</span> Yes <span class="text-strong">Registration Number</span> NCT02646826 <span class="text-strong">RCT</span> Yes <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> Western Institutional Review Board - 1019 39th Avenue SE Suite 120, Puyallup, WA 98374-2115 <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes