OBJECTIVE: To examine the safety and efficacy of mirabegron as add-on therapy to solifenacin in patients with OAB.
PATIENTS AND METHODS: This multicenter, open-label, Phase IV study enrolled patients ≥20 years old with OAB, as determined by an overactive bladder symptom score (OABSS) total score of ≥3 points and a Question 3 OABSS of ≥2 points, who were being treated with solifenacin at a stable dose of 2.5 or 5 mg once daily for at least 4 weeks. Study duration was 18 weeks, comprising a 2-week screening period and a 16-week treatment period. Patients meeting eligibility criteria continued to receive solifenacin (2.5 or 5 mg once daily), and additional mirabegron (25 mg once daily) for 16 weeks. After 8 weeks of treatment, the mirabegron dose could be increased to 50 mg if the patient's symptom improvement was not sufficient, he/she was agreeable to the dose increase, and the investigator judged that there were no safety concerns. Safety assessments included adverse events (AEs), laboratory tests, vital signs, 12-lead electrocardiogram (ECG), QT corrected for heart rate using Fridericia's correction (QTcF) interval and post-void residual (PVR) volume. Efficacy endpoints were changes from baseline in OABSS total score, overactive bladder questionnaire short form (OAB-q SF) score (symptom bother and total health-related quality of life [HRQL] score), mean number of micturitions/24 h, mean number of urgency episodes/24 h, mean number of incontinence episodes/24 h, mean number of urgency incontinence episodes/24 h, mean volume voided/micturition, and mean number of nocturia episodes/night. Patients were instructed to complete the OABSS sheets at week -2, 0, 8 and 16 (or at discontinuation), OAB-q SF sheets at week 0, 8 and 16 (or at discontinuation), and patient micturition diaries at week 0, 4,8,12 and 16 (or at discontinuation).
RESULTS: Overall incidence of drug-related TEAEs was 23.3%. Almost all TEAEs were mild or moderate. The most common TEAE was constipation, with similar incidence in the groups receiving a dose increase to that observed in the groups maintained on the original dose. Changes in post-void residual volume, QTcF interval, pulse rate, and blood pressure were not considered to be clinically significant and there were no reports of urinary retention. Significant improvement was seen for changes in efficacy endpoints from baseline to end of treatment (EOT) in all groups (patients receiving solifenacin 2.5 or 5 mg + mirabegron 25 or 50 mg).
CONCLUSIONS: Add-on therapy with mirabegron 25 mg once daily for 16 weeks, with an optional dose increase to 50 mg at week 8, was well tolerated in patients with OAB treated with solifenacin 2.5 mg or 5 mg once daily. Significant improvements from baseline to EOT in OAB symptoms were observed with combination therapy with mirabegron and solifenacin. Add-on therapy with mirabgron and an antimuscarinic agent such as solifenacin may provide an attractive therapeutic option.
Written by:
Yamaguchi O, Kakizaki H, Homma Y, Igawa Y, Takeda M, Nishizawa O, Gotoh M, Yoshida M, Yokoyama O, Seki N, Okitsu A, Hamada T, Kobayashi A, Kuroishi K. Are you the author?
Division of Bioengineering and LUTD Research, Nihon University, School of Engineering, Koriyama, Japan.
Reference: BJU Int. 2015 Jan 30. Epub ahead of print.
doi: 10.1111/bju.13068
PubMed Abstract
PMID: 25639296