Evaluation of safety and efficacy of desmopressin/tolterodine combination therapy in women.
This double‐blind, randomized, proof‐of‐concept study enrolled 106 patients (≥18 years), with overactive bladder (OAB) and nocturia, with ≥2 nocturnal voids, receiving a 3‐month once‐daily combination (desmopressin 25 µg, orally‐disintegrating tablets [ODT]/tolterodine 4 mg [Detrol® LA]; n = 49) or monotherapy (tolterodine 4 mg/placebo ODT; n = 57). Primary endpoint was change from baseline in mean number of nocturnal voids. Secondary endpoints were change from baseline in nocturnal voided volume, time to first nocturnal void, and quality‐of‐life. Post‐hoc exploratory analysis were performed for patients with and without baseline nocturnal polyuria (NP, n = 47 each).
Overall population showed a non‐significant reduction in mean number of nocturnal voids with combination versus monotherapy (full analysis set: adjusted treatment contrast [TC], −0.34; P = 0.112). Change in mean nocturnal void volume (TC, −64.16 mL; P = 0.103), mean time to first nocturnal void (TC, 18.00 min; P = 0.385) and Nocturia Impact (NI) Diary© scores were comparable. In post‐hoc analysis, NP patients showed a benefit with combination versus monotherapy for nocturnal void volume (P = 0.034) and time to first nocturnal void (P = 0.045), and a non‐significant improvement in NI Diary© scores. Safety profile was comparable between treatments. A single transient event of asymptomatic clinically significant hyponatremia in combination group resolved subsequently.
Low‐dose desmopressin could be safely combined with tolterodine for treating nocturia in women with OAB, with a significant benefit in women with NP. Further, prospective validation studies of combination therapy are warranted in mixed NP/OAB population, based on this favorable proof‐of‐concept finding.