PHILADELPHIA—In a phase 2 trial, a novel prolonged action formulation of an acetaminophen-ibuprofen combination demonstrated short-term efficacy and safety in the treatment of nocturia symptoms, investigators reported at the International Continence Society’s 2018 annual meeting.
Both drugs inhibit prostaglandins, which have been shown to have a role in modulating detrusor muscle tone and micturition and thus represent a potential therapeutic target in the treatment of nocturia, the investigators noted.
The double-blind trial, which enrolled 86 patients with nocturia, compared low, medium, and high doses of the 2-drug therapy (Paxerol) with placebo for 2 weeks. The primary outcomes were average number of nocturnal voids (ANV) and nocturia quality of life (NQOL) scores. Patients in the 4 study arms were not significantly different with regard to demographic and baseline voiding characteristics.
Compared with placebo recipients, patients treated with any Paxerol dose experienced significant decreases in the average number of nocturnal voids, Mahyar Kashan, MD, of Downstate College of Medicine in Brooklyn, New York, and colleagues reported. All study arms had a decrease in NQOL scores (reflecting improvement), but significantly larger reductions occurred in those receiving a medium and high dose of the pharmacotherapy.
Duration of first uninterrupted sleep increased (DFUS) in all 4 groups, with a significantly larger increase in the high-dose treatment arm compared with placebo. The investigators found no significant difference among the placebo and treatment arms with regard to total hours of nightly sleep (THNS).
No severe adverse events occurred, and no adverse events were believed to have been related to study drug, according to the investigators
The significant decrease in ANV in all of the Paxerol arms, combined with the significant improvement in NQOL scores in the medium and high dose Paxerol arms compared with 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.”
The observation that high dose Paxerol demonstrated a significantly increase in DFUS compared with 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.
The authors acknowledged that their study was limited by a small sample size, lack of full bladder diary parameters, and short duration of therapy.
Adrian Wagg, MB, BS, Capital Health Research Professor in Healthy Ageing at the University of Alberta in Edmonton, a co-moderator of the nocturia session at which Dr Kashan presented the study findings, said he is concerned about the potential long-term renal effects of the new therapy, “particularly where it’s being used for nocturnal polyuria, which primarily affects older people who have diminished renal function to start with.”
The mechanism of action of these drugs primarily relates to the kidney reducing nocturnal polyuria, he said. Certainly, with long-term ibuprofen use, “there is always a concern about renal toxicity or renal impairment,” he said. “It might all right for short-term use, [but] we need to be cautious about long-term use.”
Kashan M, Khusid JA, Weiss JP, et al. 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. Data presented at the International Continence Society’s 2018 annual meeting in Philadelphia,, August 28–31. Abstract 8.