Safety and efficacy of desmopressin orally disintegrating tablet 25/50µg in patients with nocturia and mild daytime urinary symptoms

Weiss J P1, Malmberg A2, Juul K V2

Research Type

Clinical

Abstract Category

Nocturia

Abstract 10
Nocturia
Scientific Podium Short Oral Session 2
Wednesday 29th August 2018
08:57 - 09:05
Hall B
Nocturia Overactive Bladder Bladder Outlet Obstruction Benign Prostatic Hyperplasia (BPH)
1. Department of Urology, SUNY Downstate College of Medicine, Brooklyn, New York, 2. Ferring Pharmaceuticals, Denmark
Presenter
J

Jeffrey P Weiss

Links

Abstract

Hypothesis / aims of study
Desmopressin orally disintegrating tablet (ODT) 25/50µg is to date approved in over 30 countries for symptomatic treatment of nocturia due to idiopathic nocturnal polyuria in adults. A large proportion of nocturia patients have idiopathic nocturnal polyuria and are therefore considered appropriate candidates for antidiuretic therapy using desmopressin. A substantial proportion of nocturia patients also have other daytime lower urinary tract symptoms (LUTS) due to overactive bladder (OAB) or benign prostatic obstruction (BPO). Little is known regarding the efficacy of desmopressin in nocturia patients with OAB or BPO, nor whether they are at risk of increased side effects with desmopressin treatment. The aim of this study was to analyse efficacy and safety data from two phase 3 trials of desmopressin ODT therapy in a subgroup of patients with nocturia and NP as well as mild daytime voiding dysfunction.
Study design, materials and methods
Data were derived from two 3-month, phase 3 double-blind randomised placebo-controlled trials of desmopressin ODT in males (50/75µg; NCT01262456) and females (25µg; NCT01223937) with ≥2 voids per night during 3-day screening. Mild daytime LUTS associated with OAB/BPO were not specifically excluded, but concomitant medications for OAB/BPO (antimuscarinics, 5 alpha-reductase inhibitors, alpha-blockers) had to be stable for 3 months prior to screening. Medical history was used to exclude severe daytime voiding dysfunction (urge urinary incontinence >1 episode/day; urgency >1 episode/day; frequency >8 daytime voids/day). Patients with severe BPO (urinary retention or post-void residual volume >250mL; surgical treatment within the past 6 months; suspicion of bladder outlet obstruction or urine flow <5 mL/s) were also excluded. Nocturnal polyuria index (NPI) was recorded at baseline, with NPI>33% indicating NP. In this post-hoc analysis, only patients who enrolled with NP were included. Based on medical history or concomitant medication, patients were grouped into those with daytime symptoms, or without daytime symptoms (referred to as “pure NP”). For males, only those randomized to placebo or 50µg (not 75µg) desmopressin are included in this analysis. Baseline characteristics, nocturnal voids and safety parameters were investigated.
Results
The subgroup used for this analysis included 196 women with “pure NP”, 35 women with NP and OAB, 152 men with “pure NP” and 75 men with NP and OAB and/or BPO. Baseline voiding characteristics for patients with and without OAB and/or BPO were similar (Table 1).

Desmopressin ODT demonstrated similar efficacy in patients with pure NP and those with NP and OAB+/BPO in terms of reduction in nocturnal voids relative to placebo and percentage of patients achieving 33% reduction in nocturnal voids (Table 2). All groups showed greater improvement with desmopressin compared with placebo. Difference vs placebo in those with OAB+/BPO did not reach statistical significance due to small sample sizes.

Mild daytime urinary symptoms did not impact treatment comparison (judged by p value of treatment by symptom subgroup factor). The non-significant p-value of the treatment effect reflects the smaller sample size in those with mild daytime symptoms. 

No worsening of daytime urinary disorders was noted from the recorded treatment-emergent adverse events. No significant increase in daytime voids was seen in any group except men with OAB+/BPO receiving desmopressin, who experienced 0.59 additional daytime voids per day. When patients with OAB/BPO were treated with the recommended gender-specific doses (25µg for women and 50µg for men), the incidence of severe (≤125mmol/L) and clinically significant (126–129mmol/L) hyponatraemia was low (Table 3), and all cases would have been captured by serum sodium monitoring.
Interpretation of results
Desmopressin demonstrates a similar safety and efficacy profile in nocturia patients with NP and mild daytime voiding dysfunction (OAB+/BPO) as in patients with pure NP. A small, clinically non-significant increase in daytime voids was observed in men with OAB+/BPO.
Concluding message
Nocturia patients with NP and mild daytime voiding dysfunction (OAB or BPO) were included in the phase III trials of desmopressin ODT for nocturia. Reduction in nocturnal voids in this subgroup was consistent with the reduction in voids for those with pure NP without daytime voiding dysfunction. No additional safety concerns were identified.
Figure 1
Figure 2
Disclosures
<span class="text-strong">Funding</span> Ferring Pharmaceuticals A/S <span class="text-strong">Clinical Trial</span> Yes <span class="text-strong">Registration Number</span> NCT01262456; NCT01223937 <span class="text-strong">RCT</span> Yes <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> Approval for each site included <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes