Marcus J Drake1, Christopher Chapple2, Roman Sokol3, Matthias Oelke4, Klaudia Traudtner5, Monique Klaver5, Ted Drogendijk5, Philip Van Kerrebroeck6. 1. University of Bristol and Bristol Urological Institute, Bristol, UK. Electronic address: Marcus.Drake@bui.ac.uk. 2. Royal Hallamshire Hospital and Sheffield Hallam University, Sheffield, UK. 3. Private Urological Care Centre, Piaristicka, Trencin, Slovakia. 4. Hannover Medical School, Hannover, Germany. 5. Astellas Pharma Global Development, Leiden, The Netherlands. 6. Maastricht University Medical Centre, Maastricht, The Netherlands.
Abstract
BACKGROUND: Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms (LUTS). The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS (oral controlled absorption system) in Males with Lower Urinary Tract Symptoms (NEPTUNE) II is the first long-term study using solifenacin (Soli) and the oral controlled absorption system formulation of tamsulosin (TOCAS). OBJECTIVE: To evaluate long-term (up to 52 wk) safety and efficacy of flexible dosing of two fixed-dose combinations (FDC) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms. DESIGN, SETTING, AND PARTICIPANTS: Patients with both storage and voiding LUTS, maximum urinary flow rate of 4.0-12.0 ml/s, prostate size <75 ml, and postvoid residuals ≤ 150 ml, who completed the 12-wk, double-blind NEPTUNE study could continue in the 40-wk, open-label NEPTUNE II study. INTERVENTION: FDC of Soli 6 mg plus TOCAS 0.4 mg, or Soli 9 mg plus TOCAS 0.4mg; patients could switch between doses in NEPTUNE II. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Safety and efficacy data from NEPTUNE and NEPTUNE II were combined to cover a 52-wk period. Primary efficacy end points were total International Prostate Symptom Score (IPSS) and total urgency and frequency score (TUFS); secondary end points included IPSS storage and voiding subscores, micturition diary variables, and quality of life parameters. RESULTS: In all, 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II. Treatment-emergent adverse events were reported in 499 (46.8%) patients who participated in NEPTUNE II; most were mild or moderate. Urinary retention occurred in 13 of 1208 (1.1%) patients receiving one or more FDCs in NEPTUNE and/or NEPTUNE II; 8 (0.7%) required catheterisation (acute urinary retention [AUR]). Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment, with mean reductions of 9.0 (standard deviation [SD]: 5.7) and 10.1 (SD: 9.2), respectively, from baseline to end of treatment. Clinically relevant improvements were also observed for secondary efficacy end points. CONCLUSIONS: Long-term treatment with FDC Soli plus TOCAS was well tolerated and efficacious in men with storage and voiding LUTS, with a low incidence of AUR. PATIENT SUMMARY: Treatment with solifenacin plus tamsulosin in a fixed-dose combination tablet was well tolerated by men with lower urinary tract symptoms. Improvements in symptoms were achieved after 4 wk of treatment, with further improvements at week 16 maintained for up to 52 wk throughout the study.
RCT Entities:
BACKGROUND: Short-term trials have demonstrated the efficacy and safety of combination therapy using antimuscarinics and α-blockers in men with lower urinary tract symptoms (LUTS). The Study of Solifenacin Succinate and Tamsulosin Hydrochloride OCAS (oral controlled absorption system) in Males with Lower Urinary Tract Symptoms (NEPTUNE) II is the first long-term study using solifenacin (Soli) and the oral controlled absorption system formulation of tamsulosin (TOCAS). OBJECTIVE: To evaluate long-term (up to 52 wk) safety and efficacy of flexible dosing of two fixed-dose combinations (FDC) of Soli plus TOCAS in men with moderate to severe storage symptoms and voiding symptoms. DESIGN, SETTING, AND PARTICIPANTS: Patients with both storage and voiding LUTS, maximum urinary flow rate of 4.0-12.0 ml/s, prostate size <75 ml, and postvoid residuals ≤ 150 ml, who completed the 12-wk, double-blind NEPTUNE study could continue in the 40-wk, open-label NEPTUNE II study. INTERVENTION: FDC of Soli 6 mg plus TOCAS 0.4 mg, or Soli 9 mg plus TOCAS 0.4mg; patients could switch between doses in NEPTUNE II. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Safety and efficacy data from NEPTUNE and NEPTUNE II were combined to cover a 52-wk period. Primary efficacy end points were total International Prostate Symptom Score (IPSS) and total urgency and frequency score (TUFS); secondary end points included IPSS storage and voiding subscores, micturition diary variables, and quality of life parameters. RESULTS: In all, 1066 men completed NEPTUNE and received one dose or more of study medication in NEPTUNE II. Treatment-emergent adverse events were reported in 499 (46.8%) patients who participated in NEPTUNE II; most were mild or moderate. Urinary retention occurred in 13 of 1208 (1.1%) patients receiving one or more FDCs in NEPTUNE and/or NEPTUNE II; 8 (0.7%) required catheterisation (acute urinary retention [AUR]). Reductions in total IPSS and TUFS during NEPTUNE were maintained for up to 52 wk of FDC treatment, with mean reductions of 9.0 (standard deviation [SD]: 5.7) and 10.1 (SD: 9.2), respectively, from baseline to end of treatment. Clinically relevant improvements were also observed for secondary efficacy end points. CONCLUSIONS: Long-term treatment with FDC Soli plus TOCAS was well tolerated and efficacious in men with storage and voiding LUTS, with a low incidence of AUR. PATIENT SUMMARY: Treatment with solifenacin plus tamsulosin in a fixed-dose combination tablet was well tolerated by men with lower urinary tract symptoms. Improvements in symptoms were achieved after 4 wk of treatment, with further improvements at week 16 maintained for up to 52 wk throughout the study.
Authors: J Curtis Nickel; Lorne Aaron; Jack Barkin; Dean Elterman; Mahmoud Nachabé; Kevin C Zorn Journal: Can Urol Assoc J Date: 2018-10 Impact factor: 1.862
Authors: Philipp Dahm; Michelle Brasure; Roderick MacDonald; Carin M Olson; Victoria A Nelson; Howard A Fink; Bruce Rwabasonga; Michael C Risk; Timothy J Wilt Journal: Eur Urol Date: 2016-10-04 Impact factor: 20.096