Abstract: PD26-06
Sources of Funding: Astellas Pharma Europe Ltd.

Introduction

Older overactive bladder (OAB) patients usually have more symptom severity, comorbidity, and poorer quality of life vs younger patients. We report efficacy/safety/tolerability of solifenacin (SOLI) + mirabegron (MIRA) vs SOLI alone in older incontinent OAB patients refractory to SOLI monotherapy from BESIDE, a randomized, double-blind, parallel group multicenter Phase 3B study (NCT01908829).

Methods

Adults with ≥3 months of OAB and an average of ≥2 incontinence episodes/24h entered a 2-week screening/washout period before a 4-week run-in of single-blind daily SOLI 5mg. Patients remaining incontinent at baseline (BL; ≥1 episode during a 3-day diary) were randomized 1:1:1 to daily double-blind combination (COMBN; SOLI 5mg+MIRA 25mg, increased to 50mg at Week 4), SOLI 5mg or 10mg for 12 weeks. Primary endpoint was change from BL to end of treatment (EOT) in mean number of incontinence episodes/24h. Safety assessment included frequency of treatment-emergent adverse events (TEAEs). Pre-defined age subgroup data are reported for patients aged <65y, ≥65y, <75y, and ≥75y.

Results

Reductions in mean number of incontinence episodes/24h and micturitions/24h from BL to EOT were greater with COMBN vs SOLI monotherapy across subgroups. Incontinence treatment differences between COMBN and SOLI 5mg, and micturition frequency differences between COMBN and SOLI monotherapy were consistent across subgroups, however the difference in incontinence between COMBN and SOLI 10mg was more pronounced in patients aged ≥65y and ≥75y (Table). Overall the frequency of TEAEs was higher in older subgroups. Overall the frequency of TEAEs was lower with COMBN and SOLI 5mg vs SOLI 10mg, respectively, in each subgroup (<65y [34.4 and 30.3 vs 35.2%], ≥65y [39.0 and 39.4 vs 48.7%], <75y [35.4 and 32.3 vs 38.6%] and ≥75y [39.7 and 40.9 vs 49.1%]). The most common group of TEAEs with COMBN, SOLI 5mg and 10mg, respectively, was gastrointestinal disorders which occurred more often in the older subgroups (<65y [13.4 vs 12.0 and 15.2%], ≥65y [15.2 vs 13.3 and 20.5%], <75y [14.0 vs 12.2 and 16.6%] and ≥75y [13.7 vs 13.6 and 20.0%]).

Conclusions

Combination therapy with SOLI 5mg+MIRA 50mg provides additional treatment benefit vs SOLI monotherapy in incontinent older OAB patients with an insufficient response to SOLI 5mg.

Funding

Astellas Pharma Europe Ltd.