Novel immediate/sustained-release formulation of acetaminophen-ibuprofen combination (Paxerol®) for severe nocturia associated with overactive bladder: A multi-center, randomized, double blinded, placebo-controlled, 4-arm trial

Abstract

Aim: To determine short-term efficacy and safety of Paxerol®, novel immediate:sustained (50%:50%) release tablets containing 325 mg acetaminophen and 150 mg ibuprofen per tablet.

Methods: One of three dose levels, corresponding to the amounts in 1, 2, and 3 tablets, of Paxerol and placebo were administered for 14 consecutive days to patients with severe nocturia (defined in this study as an average nocturnal voids [NV] ≥2.5) associated with overactive bladder (OAB). Changes in NV, as well as Nocturia Quality of Life (NQOL), duration of first uninterrupted sleep (DFUS), and total hours of nightly sleep (THNS) associated with treatment were assessed. Short-term safety/tolerability was assessed throughout the study and for at least 30 days post-treatment.

Results: Paxerol at all three doses reduced NV to a greater degree than placebo (average NV -1.1, -1.4, -1.3 voids for low, mid, and high doses, respectively, vs -0.3 void for placebo). NQOL and THNS were similar between baseline and treatment values in all four groups. There were also no between-group differences. Paxerol at high dose tended to (although not statistical significantly) increase DFUS to a greater degree than placebo (1.2 vs 0.4 h, P = 0.057). There were no treatment related adverse events in any of the four groups.

Conclusions: This study demonstrates short-term efficacy and short-term safety of Paxerol in patients with severe nocturia associated with OAB. The results warrant further investigation of the long-term efficacy and safety of Paxerol in larger patient populations.

Trial registration: ClinicalTrials.gov NCT02646826.

Keywords: clinical trial; investigational drug; nocturia; prostagladin-E2 inhibitors.

© 2018 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.

Figures

Figure 1

A, Schematic outline of the study procedures for the prospective, multi‐center, double blind, placebo‐controlled, four‐arm Phase 2 trial of Paxerol. B, Disposition of study subjects during the study in the prospective, multi‐center, double‐blind, placebo‐controlled, four‐arm Phase 2 trial of Paxerol. AE, adverse event; Ave, average; DFUS, duration of first undisturbed sleep; NQOL, nocturia‐quality‐of‐life; THNS, total hours of nightly sleep

Figure 2

Percent changes (mean ± SEM) in nightly voids by study day in the four treatment groups: placebo and Paxerol at low, mid and high doses. N, sample size; SEM, standard error of the mean. The P‐values were from a mixed‐effect model repeated measures, adjusted for multiple comparisons with Dunnett's method