title: Long-term safety and efficacy of single-tablet combinations of solifenacin and tamsulosin oral controlled absorption system in men with storage and voiding lower urinary tract symptoms: results from the NEPTUNE Study and NEPTUNE II open-label extension.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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: University of Bristol and Bristol Urological Institute, Bristol, UK. Electronic address: Marcus.Drake@bui.ac.uk.
authors: Marcus J
authors: MJ
authors: Drake
authors: Royal Hallamshire Hospital and Sheffield Hallam University, Sheffield, UK.
authors: Christopher
authors: C
authors: Chapple
authors: Private Urological Care Centre, Piaristicka, Trencin, Slovakia.
authors: Roman
authors: R
authors: Sokol
authors: Hannover Medical School, Hannover, Germany.
authors: Matthias
authors: M
authors: Oelke
authors: Astellas Pharma Global Development, Leiden, The Netherlands.
authors: Klaudia
authors: K
authors: Traudtner
authors: Astellas Pharma Global Development, Leiden, The Netherlands.
authors: Monique
authors: M
authors: Klaver
authors: Astellas Pharma Global Development, Leiden, The Netherlands.
authors: Ted
authors: T
authors: Drogendijk
authors: Maastricht University Medical Centre, Maastricht, The Netherlands.
authors: Philip
authors: P
authors: Van Kerrebroeck
mesh_terms: D000284:Administration, Oral; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D002626:Chemistry, Pharmaceutical; D004311:Double-Blind Method; D004338:Drug Combinations; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D000069464:Solifenacin Succinate / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D013607:Tablets; D000077409:Tamsulosin; D013997:Time Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016055:Urinary Retention / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects; D064804:Urological Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D013449:Sulfonamides; D013607:Tablets; D064804:Urological Agents; D000077409:Tamsulosin; D000069464:Solifenacin Succinate
keywords: Benign prostatic hyperplasia; Clinical trial; Lower urinary tract symptoms; Muscarinic antagonist; Phase 3; Solifenacin; Tamsulosin OCAS; α-Adrenergic blocker