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Christopher R Chapple - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and efficacy of mirabegron and Solifenacin in combination compared with monotherapy in patients with overactive bladder a randomised multicentre phase 3 study synergy ii
    European Urology, 2018
    Co-Authors: Christian Gratzke, Christopher R Chapple, Sender Herschorn, Arwin Ridder, Paul Abrams, Asha Paireddy, Rob Van Maanen, Dudley Robinson, Matthias Stoelzel, Sang Jin Yoon
    Abstract:

    Abstract Background The long-term potential of Solifenacin and mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of Solifenacin succinate 5mg plus mirabegron 50mg tablets (combination treatment) versus Solifenacin or mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; mirabegron 126 patients, 41%; Solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; Solifenacin 18 patients, 5.9%; mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to mirabegron and Solifenacin for the number of incontinence episodes (vs mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p Conclusions Mirabegron and Solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of Solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with Solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

  • Cardiovascular safety in refractory incontinent patients with overactive bladder receiving add-on mirabegron therapy to Solifenacin (BESIDE)
    International journal of clinical practice, 2017
    Co-Authors: Marcus J Drake, Christopher R Chapple, Adil Esen, Stavros Athanasiou, David Mitcheson, Sender Herschorn, Emad Siddiqui, Scott Macdiarmid, Javier Cambronero Santos, Moses Huang
    Abstract:

    © 2017 John Wiley & Sons Ltd.Summary : Aims/objectives: : In the BESIDE study, combination therapy (antimuscarinic [Solifenacin] and β3-adrenoceptor agonist [mirabegron]) improved efficacy over Solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder (OAB) patients; however, a potential synergistic effect on the cardiovascular (CV) system requires investigation. Methods: OAB patients remaining incontinent despite daily Solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (Solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), Solifenacin 5 or 10 mg for 12 weeks. CV safety assessments included frequency of CV-related treatment-emergent adverse events (TEAEs), change from baseline in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and electrocardiogram (ECG) parameters. Results: The frequency of hypertension, tachycardia and ECG QT prolongation, respectively, was low and comparable across combination (1.1%, 0.3%, 0.1%), Solifenacin 5 mg (0.7%, 0.1%, 0.1%), and Solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination (0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), Solifenacin 5 mg (-0.93 mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and Solifenacin 10 mg (-1.28 mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and Solifenacin monotherapy; SBP was unchanged with combination and decreased with Solifenacin monotherapy. Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups, except for QT interval corrected using Fridericia's formula, which was higher with Solifenacin 10 mg (3.30 mseconds) vs. combination (0.49 mseconds) and Solifenacin 5 mg (0.77 mseconds). Conclusion: The comparable frequency of CV-related TEAEs, changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and Solifenacin are combined.

  • pooled Solifenacin overactive bladder trial data creation validation and analysis of an integrated database
    Contemporary clinical trials communications, 2016
    Co-Authors: Christopher R Chapple, Emad Siddiqui, Linda Cardozo, Robert Snijder, Sender Herschorn
    Abstract:

    Abstract Background Patient-level data are available for 11 randomized, controlled, Phase III/Phase IV Solifenacin clinical trials. Methods Meta-analyses were conducted to interrogate the data, to broaden knowledge about Solifenacin and overactive bladder (OAB) in general. Before integrating data, datasets from individual studies were mapped to a single format using methodology developed by the Clinical Data Interchange Standards Consortium (CDISC). Initially, the data structure was harmonized, to ensure identical categorization, using the CDISC Study Data Tabulation Model (SDTM). To allow for patient level meta-analysis, data were integrated and mapped to analysis datasets. Mapping included adding derived and categorical variables and followed standards described as the Analysis Data Model (ADaM). Mapping to both SDTM and ADaM was performed twice by two independent programming teams, results compared, and inconsistencies corrected in the final output. ADaM analysis sets included assignments of patients to the Safety Analysis Set and the Full Analysis Set. Results There were three analysis groupings: Analysis group 1 (placebo-controlled, monotherapy, fixed-dose studies, n = 3011); Analysis group 2 (placebo-controlled, monotherapy, pooled, fixed- and flexible-dose, n = 5379); Analysis group 3 (all Solifenacin monotherapy-treated patients, n = 6539). Treatment groups were: Solifenacin 5 mg fixed dose, Solifenacin 5/10 mg flexible dose, Solifenacin 10 mg fixed dose and overall Solifenacin. Patient were similar enough for data pooling to be acceptable. Conclusions Creating ADaM datasets provided significant information about individual studies and the derivation decisions made in each study; validated ADaM datasets now exist for medical history, efficacy and AEs. Results from these meta-analyses were similar over time.

  • efficacy and safety of mirabegron add on therapy to Solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4 week Solifenacin monotherapy a randomised double blind multicentre phase 3b study beside
    European Urology, 2016
    Co-Authors: Marcus J Drake, Christopher R Chapple, Adil Esen, Stavros Athanasiou, Javier Cambronero, David Mitcheson, Sender Herschorn, Tahir Saleem, Moses Huang, Emad Siddiqui
    Abstract:

    Background Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy. Objective To evaluate the efficacy and the safety and tolerability of combination (Solifenacin 5mg and mirabegron 50mg) versus Solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of Solifenacin 5mg. Design, setting, and participants OAB patients remaining incontinent despite daily Solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or Solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4. Outcome measurements and statistical analysis The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (Solifenacin plus mirabegron) with one treatment alone (Solifenacin) tested the superiority of combination versus Solifenacin 5mg, noninferiority (and potential superiority) of combination versus Solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus Solifenacin monotherapy. Results and limitations A total of 2174 patients were randomised to combination (n=727), Solifenacin 5mg (n=728), or Solifenacin 10mg (n=719). At EOT, combination was superior to Solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p Conclusions Adding mirabegron 50mg to Solifenacin 5mg further improved OAB symptoms versus Solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial Solifenacin 5mg. Patient summary In this 12-wk study, overactive bladder patients who remained incontinent despite initial Solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with Solifenacin 5mg was superior to Solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated. Trial registration ClinicalTrials.gov NCT01908829.

  • combination therapy with Solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men efficacy and safety results from the randomised controlled neptune trial
    European Urology, 2013
    Co-Authors: Philip Van Kerrebroeck, Christopher R Chapple, T. Drogendijk, Monique Klaver, Roman Sokol, Mark Speakman, Klaudia Traudtner, Marcus J Drake
    Abstract:

    Abstract Background Storage symptoms are particularly bothersome in men with lower urinary tract symptoms (LUTS) but may not be adequately treated by α-blocker monotherapy. Objective To assess the efficacy and safety of a fixed-dose combination (FDC) of Solifenacin and an oral controlled absorption system (OCAS) formulation of tamsulosin compared with placebo and compared with tamsulosin OCAS (TOCAS) monotherapy in men with moderate to severe storage symptoms and voiding symptoms. Design, setting, and participants A double-blind 12-wk phase 3 study in 1334 men with storage and voiding LUTS: total International Prostate Symptom Score (IPSS) ≥13, maximum urinary flow rate (Q max ) 4.0–12.0ml/s, two or more urgency episodes per 24 h of Patient Perception of Intensity of Urgency Scale grade 3 or 4, and eight or more micturitions per 24h. Intervention Patients were randomised to placebo, TOCAS 0.4mg, FDC Solifenacin 6mg plus TOCAS 0.4mg, or FDC Solifenacin 9mg plus TOCAS 0.4mg. Outcome measurements and statistical analysis Primary efficacy end points were (1) total IPSS and (2) Total Urgency and Frequency Score (TUFS). An FDC met the success criteria if it demonstrated superiority compared with placebo and noninferiority compared with TOCAS for total IPSS, as well as superiority compared with TOCAS for TUFS. Results and limitations Reductions in total IPSS and TUFS were observed with both Solifenacin 6mg plus TOCAS (−7.0 and −8.1, respectively) and Solifenacin 9mg plus TOCAS (−6.5 and −7.6, respectively) compared with TOCAS (−6.2 and −6.7, respectively) and placebo (−5.4 and −4.4, respectively). Solifenacin 6mg plus TOCAS met all prespecified success criteria for both primary end points, while Solifenacin 9mg plus TOCAS met success criteria compared with placebo but not compared with TOCAS. Both FDCs improved quality of life (QoL) measures and were well tolerated, with low incidences of acute urinary retention. Conclusions The FDC of Solifenacin 6mg plus TOCAS significantly improved storage and voiding symptoms, as well as QoL parameters, compared with placebo. This FDC also improved storage symptoms and QoL compared with TOCAS alone in men with moderate to severe storage symptoms and voiding symptoms, and it was well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT01018511).

Arwin Ridder - One of the best experts on this subject based on the ideXlab platform.

  • long term safety and efficacy of mirabegron and Solifenacin in combination compared with monotherapy in patients with overactive bladder a randomised multicentre phase 3 study synergy ii
    European Urology, 2018
    Co-Authors: Christian Gratzke, Christopher R Chapple, Sender Herschorn, Arwin Ridder, Paul Abrams, Asha Paireddy, Rob Van Maanen, Dudley Robinson, Matthias Stoelzel, Sang Jin Yoon
    Abstract:

    Abstract Background The long-term potential of Solifenacin and mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. Objectives To evaluate the safety and efficacy of Solifenacin succinate 5mg plus mirabegron 50mg tablets (combination treatment) versus Solifenacin or mirabegron monotherapy in patients with OAB over 12 mo. Design, setting, and participants Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. Outcome measurements and statistical analysis The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. Results and limitations The median age was 60 yr (range 19–86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; mirabegron 126 patients, 41%; Solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; Solifenacin 18 patients, 5.9%; mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to mirabegron and Solifenacin for the number of incontinence episodes (vs mirabegron: adjusted mean difference [AMD] −0.5, 95% confidence interval [CI] −0.7 to −0.2, p Conclusions Mirabegron and Solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. Patient summary This study looked at the safety and efficacy of a combination of Solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with Solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862.

  • combination treatment with mirabegron and Solifenacin in patients with overactive bladder efficacy and safety results from a randomised double blind dose ranging phase 2 study symphony
    European Urology, 2015
    Co-Authors: Paul Abrams, Donald Newgreen, Con Kelleher, David R Staskin, Tomasz Rechberger, Richard Kay, R Martina, Asha Paireddy, Rob Van Maanen, Arwin Ridder
    Abstract:

    Abstract Background Combining the β3-adrenoceptor agonist mirabegron and the antimuscarinic (AM) agent Solifenacin may improve efficacy in the treatment of overactive bladder (OAB) while reducing the AM side effects. Objective The primary objective was to evaluate the efficacy of combinations of Solifenacin/mirabegron compared with Solifenacin 5mg monotherapy. The secondary objective was to explore the dose–response relationship and the safety/tolerability compared with placebo and monotherapy. Design, setting, and participants A phase 2, factorial design, randomised, double-blind, parallel-group, placebo- and monotherapy-controlled trial, conducted at 141 sites in 20 European countries. Male and female patients were aged ≥18 yr with symptoms of OAB for ≥3 mo. Intervention A total of 1306 patients (66.4% female) were randomised to 12 wk of treatment in 1 of 12 groups: 6 combination groups (Solifenacin 2.5, 5, or 10mg plus mirabegron 25 or 50mg), 5 monotherapy groups (Solifenacin 2.5, 5, or 10mg, or mirabegron 25 or 50mg), or placebo. Outcome measurements and statistical analysis Change from baseline to end of treatment in mean volume voided per micturition (MVV) (primary end point) and mean numbers of micturitions per 24h, incontinence episodes per 24h, and urgency episodes per 24h were analysed using an analysis of covariance model. Safety assessments included treatment-emergent adverse events (TEAEs), blood pressure, pulse rate, postvoid residual (PVR) volume, and laboratory and electrocardiography (ECG) parameters. Results and limitations Compared with Solifenacin 5mg monotherapy, all combinations with Solifenacin 5 or 10mg significantly improved MVV, with adjusted differences ranging from 18.0ml (95% confidence interval [CI], 5.4–30.0) to 26.3ml (95% CI, 12.0–41.0). Three combination groups significantly reduced micturition frequency compared with Solifenacin 5mg, ranging from −0.80 (95% CI, −1.39 to −0.22) to −0.98 (95% CI, −1.68 to −0.27). Five of six combinations significantly reduced urgency episodes compared with Solifenacin 5mg, ranging from −0.98 (95% CI, −1.78, to −0.18) to −1.37 (95% CI, −2.03 to −0.70). No dose-related trends in TEAEs, blood pressure, pulse rate, PVR volume, or laboratory or ECG parameters were observed between combination and monotherapy groups, although the incidence of constipation was slightly increased with combination therapy. Conclusions Combination therapy with Solifenacin/mirabegron significantly improved MVV, micturition frequency, and urgency compared with Solifenacin 5mg monotherapy. All combinations were well tolerated, with no important additional safety findings compared with monotherapy or placebo. Patient summary To improve treatment of overactive bladder (OAB), mirabegron/Solifenacin in combination was compared with each drug alone and placebo. Combination therapy improved OAB symptoms and had similar safety and acceptability. Trial registration Clinical trials.gov: NCT01340027.

  • reductions in overactive bladder related incontinence from pooled analysis of phase iii trials evaluating treatment with Solifenacin
    International Urogynecology Journal, 2006
    Co-Authors: Linda Cardozo, Arwin Ridder, David Castrodiaz, Marc Gittelman, Moses Huang
    Abstract:

    The embarrassment and social stigma associated with urinary incontinence (UI) in overactive bladder syndrome (OAB) sufferers is a major reason for individuals to seek help for their condition. An analysis of 1,873 subjects with OAB with UI was conducted to assess the efficacy of Solifenacin in reducing incontinence in a pooled population from four phase III clinical trials, stratified by severity of incontinence, urgency, and other key factors at baseline. Subjects were randomized to either 5 or 10 mg of Solifenacin once daily or placebo for 12 weeks. More than 50% of the total population became continent at study end, with either dose of Solifenacin (P<0.01 vs placebo). Significant reductions in incontinence episodes and higher rates of attainment of continence vs placebo were observed irrespective of age or severity of incontinence or urgency at baseline with Solifenacin treatment. Treatment was well tolerated, with the majority of adverse events being mild in nature. Solifenacin is an effective antimuscarinic agent for the treatment of incontinence associated with OAB.

  • long term open label Solifenacin treatment associated with persistence with therapy in patients with overactive bladder syndrome
    European Urology, 2005
    Co-Authors: Francois Haab, Christopher R Chapple, Linda Cardozo, Arwin Ridder
    Abstract:

    Abstract Objective: To examine safety and tolerability findings as primary endpoints, and efficacy outcomes as secondary endpoints, of Solifenacin treatment over a period of up to 1 year. Long-term efficacy in the treatment of overactive bladder (OAB) syndrome depends in part on the patient's persistence with pharmacologic therapy. Agents with a favourable therapeutic index supporting high levels of patient satisfaction and persistence are needed. Methods: The present study was a 40-week open-label extension of two 12-week, placebo-controlled, double-blind studies of Solifenacin treatment in patients with OAB. Patients who completed the 12-week studies were offered participation in the open-label extension study. All patients who entered the open-label extension study initially received Solifenacin 5mg daily for 4 weeks, after which a flexible dosing regimen allowed patients to individualise their treatment (5mg or 10mg) at each of the 3 study visits. Safety and tolerability assessments (the primary variable) included adverse event reporting. Efficacy data were collected from micturition diaries completed at weeks 16, 28, 40, and 52. Results: Ninety-one percent (1637/1802) of patients who completed the two 12-week randomised studies chose to participate in the long-term open-label extension study. A total of 81% of patients completed 40 weeks of open-label treatment. Solifenacin treatment was safe and well tolerated, and rates of anticholinergic side effects were relatively low. Only 4.7% of patients discontinued treatment owing to adverse events. Improvements in major symptoms of OAB were noted for all patients for up to 52 weeks of treatment. In patients randomised to Solifenacin in the double-blind studies, there were small incremental improvements in all efficacy parameters (reductions in episodes per 24hours of urgency, reductions in frequency and urge incontinence, and increases in volume voided per micturition) over the course of the extension study. Efficacy was confirmed when outcomes were assessed as a function of total Solifenacin exposure. Patient satisfaction with Solifenacin tolerability (85%) and efficacy (74%) were high. These results indicate that long-term treatment with Solifenacin was well tolerated and associated with improvements in efficacy parameters based on patient diary data recorded over the 12-month treatment period. Moreover, the high level of patient satisfaction reported appeared to correlate well with the quantified improvements in key symptoms demonstrated in this study. Conclusions: Long-term therapy with Solifenacin resulted in a favourable tolerability profile, and was associated with improvements in efficacy parameters based on diary data recorded over a 12-month period. This balance of tolerability and efficacy with Solifenacin was associated with excellent persistence with therapy. These results suggest that Solifenacin may be useful for the long-term treatment of the chronic symptoms associated with OAB.

  • improved quality of life in patients with overactive bladder symptoms treated with Solifenacin
    BJUI, 2005
    Co-Authors: Con Kelleher, Christopher R Chapple, Linda Cardozo, Francois Haab, Arwin Ridder
    Abstract:

    OBJECTIVE To assess the effect of Solifenacin succinate treatment on quality of life (QoL) measured in clinical trials in patients with overactive bladder (OAB). PATIENTS AND METHODS QoL data using the King's Health Questionnaire (KHQ) were analysed from two phase-3, 12-week studies (1984 patients) and a long-term extension of these studies (1637 patients) where patients received Solifenacin for up to an additional 40 weeks (i.e. a 52-week exposure to Solifenacin). The 12-week studies were multinational, multicentre, randomized, double-blind, and placebo-controlled. The 10 domains from the KHQ evaluated were general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep/energy, severity measures, and symptom severity. Changes from baseline to endpoint in QoL variables were assessed by analysis of variance, and from pooled outcomes of the 12-week studies by analysis of covariance. Descriptive statistics were used to evaluate data in the extension study. RESULTS In the two 12-week studies (1033 and 857 patients), those receiving once-daily Solifenacin had statistically significantly better QoL than those on placebo. Changes in the KHQ were statistically significantly (P < 0.05) different from placebo for both Solifenacin 5 and 10 mg once daily on five of the 10 KHQ domains in each of the studies. Pooled data from the two 12-week studies showed statistically significant (P < 0.05) differences from placebo for both Solifenacin doses in nine of the 10 domains. Improvements in QoL scores for Solifenacin were 35–48% in nine of the 10 domains for the 1347 patients providing QoL data in the extension study. About two-thirds of this overall improvement occurred during the original 12-week study, with an additional third reported during the extension, with an improvement in QoL over time in patients treated with Solifenacin. CONCLUSIONS Results from the KHQ in study participants in the two double-blind studies showed that Solifenacin significantly improved the QoL in patients with OAB symptoms after 12 weeks of treatment, with further improvements during long-term administration up to 1 year. Clinical trial outcomes show a favourable balance of efficacy and tolerability with Solifenacin; the present report further supports this efficacy and tolerability by providing evidence for both short- and long-term improvements in QoL.

J Bolodeoku - One of the best experts on this subject based on the ideXlab platform.

  • exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of Solifenacin 10 mg
    Expert Opinion on Drug Safety, 2009
    Co-Authors: Keith Wesnes, Reiner Tretter, Chris Edgar, J Bolodeoku
    Abstract:

    Objectives: To assess the cognitive effects of single doses of Solifenacin 10 mg compared with placebo (primary objective) and oxybutynin immediate release (IR) 10 mg (secondary objective) in elderly subjects. Methods: Single-centre, randomised, double-blind, placebo-controlled study in 12 healthy elderly volunteers, with three crossover periods separated by two 14-day washout periods. Each sequence consisted of a single dose of Solifenacin 10 mg in one period, oxybutynin IR 10 mg in another and placebo in another. Aspects of attention, information processing, working memory, episodic memory and self-rated mood and alertness were tested using the validated Cognitive Drug Research computerised assessment system. Results: There was no evidence from absolute mean values or changes from baseline to suggest that Solifenacin 10 mg impaired cognition or self-ratings of mood and alertness versus placebo. Post-hoc ANCOVA showed no statistically significant cognitive deterioration with Solifenacin versus placebo, w...

  • treatment outcomes in the star study a subanalysis of Solifenacin 5 mg and tolterodine er 4 mg
    European Urology, 2007
    Co-Authors: Christopher R Chapple, Aino Fianujonsson, Mark Indig, Vik Khullar, Jose Rosa, Roberto Mario Scarpa, Arun Mistry, Mark D Wright, J Bolodeoku
    Abstract:

    Abstract Objective To compare OAB symptom outcomes following initial randomised treatment with Solifenacin 5mg or tolterodine ER 4mg at the 4-week clinic-visit and again at 12 weeks for patients choosing to remain on this treatment dose from 4 weeks. Methods A prospective, double blind, double-dummy, two-arm, parallel-group, 12-week study (The STAR study) was conducted to compare the efficacy and safety of Solifenacin 5/10mg and tolterodine extended release (ER) 4mg in OAB patients. Results At 4 weeks mean improvements in OAB symptoms, including urgency, frequency (primary variable), incontinence and nocturia, were larger in patients randomised to Solifenacin 5mg; with the difference for incontinence being statistically significant (mean reduction in incontinence episodes/24hrs in the Solifenacin group of −1.30 vs. −0.90 ( p =0.0181); the mean result for Solifenacin 5mg amounted to a 44% additional improvement.) There was an associated significant reduction in pad use (reduced by −1.21 vs. −0.80; p =0.0089); the mean result for Solifenacin 5mg amounted to a 51% additional improvement over that of tolterodine ER 4mg. For patients choosing to remain on these treatments improvements in favour of Solifenacin were maintained at study end (12-weeks). Treatments were well tolerated. Conclusions Within 4 weeks Solifenacin 5mg was statistically significantly better than tolterodine ER 4mg in improving incontinence and reducing incontinence pad use. Differences in efficacy in favour of Solifenacin 5mg were maintained from 4 weeks for the duration of the study for patients choosing to remain on their starting dose.

  • a comparison of the efficacy and tolerability of Solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome results of the star trial
    European Urology, 2005
    Co-Authors: Christopher R Chapple, T. Drogendijk, Roberto Martinezgarcia, L Selvaggi, Philip Toozshobson, W Warnack, D M Wright, J Bolodeoku
    Abstract:

    Abstract Objective: To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome (OAB). Methods: A prospective, double blind, double-dummy, two-arm, parallel-group, 12-week study was conducted to compare the efficacy and safety of Solifenacin 5 or 10mg and tolterodine extended release (ER) 4mg once daily in OAB patients. After 4 weeks of treatment patients had the option to request a dose increase but were dummied throughout as approved product labelling only allowed an increase for those on Solifenacin. Results: Solifenacin, with a flexible dosing regimen, showed greater efficacy to tolterodine in decreasing urgency episodes, incontinence, urge incontinence and pad usage and increasing the volume voided per micturition. More Solifenacin treated patients became continent and reported improvements in perception of bladder condition assessments. The majority of side effects were mild to moderate in nature, and discontinuations were comparable and low in both groups. Conclusions: Solifenacin, with a flexible dosing regimen, was found to be superior to tolterodine ER with respect to the majority of the efficacy variables.

Tengkai Yang - One of the best experts on this subject based on the ideXlab platform.

  • Solifenacin improves double j stent related symptoms in both genders following uncomplicated ureteroscopic lithotripsy
    Urological Research, 2013
    Co-Authors: Yuanju Lee, Kuohow Huang, Hungju Yang, Hongchiang Chang, Jun Chen, Tengkai Yang
    Abstract:

    The objective of this study is to evaluate the effects of Solifenacin on double-J stent-related symptoms following uncomplicated ureterosocpic lithotripsy (URSL). A total of 70 patients who underwent double-J ureteral stent insertion following URSL were consecutively recruited and received Solifenacin postoperatively. Another 70 age- and sex-matched subjects without Solifenacin therapy were enrolled as a control group. The clinical data including stone and stent characteristics were collected. All subjects completed the brief-form Ureteral Symptom Score Questionnaire (Chinese-version) to assess the lower urinary tract symptoms, stent-related body pain and hematuria 2 weeks after operation. The severity of stent-related symptoms was compared between two groups. The mean age was 53.8 in Solifenacin group and 53.4 years in the control group (p = 0.87). The stone characteristics, stent size, position and curl completeness were similar in both groups. Compared to the control group, Solifenacin group had significantly lower total symptom score, urgency and urge incontinence scores. As for stent-related body pain, Solifenacin group had significantly less flank, abdominal, urethral pain and hematuria scores (all p < 0.05). The Solifenacin versus control group showed significant benefits in lower urinary tract symptoms, stent-related pain and hematuria in both genders (all p < 0.05). Four subjects encountered minor adverse events (5.7 %) and one had urinary retention (1.4 %) in Solifenacin group. For patients undergoing URSL and double-J stent indwelling, postoperative Solifenacin use was effective and well-tolerated for the treatment of lower urinary tract symptoms, stent-related body pain and hematuria irrespective of genders.

  • Solifenacin improves double-J stent-related symptoms in both genders following uncomplicated ureteroscopic lithotripsy.
    Urolithiasis, 2013
    Co-Authors: Yuanju Lee, Kuohow Huang, Hungju Yang, Hongchiang Chang, Jun Chen, Tengkai Yang
    Abstract:

    The objective of this study is to evaluate the effects of Solifenacin on double-J stent-related symptoms following uncomplicated ureterosocpic lithotripsy (URSL). A total of 70 patients who underwent double-J ureteral stent insertion following URSL were consecutively recruited and received Solifenacin postoperatively. Another 70 age- and sex-matched subjects without Solifenacin therapy were enrolled as a control group. The clinical data including stone and stent characteristics were collected. All subjects completed the brief-form Ureteral Symptom Score Questionnaire (Chinese-version) to assess the lower urinary tract symptoms, stent-related body pain and hematuria 2 weeks after operation. The severity of stent-related symptoms was compared between two groups. The mean age was 53.8 in Solifenacin group and 53.4 years in the control group (p = 0.87). The stone characteristics, stent size, position and curl completeness were similar in both groups. Compared to the control group, Solifenacin group had significantly lower total symptom score, urgency and urge incontinence scores. As for stent-related body pain, Solifenacin group had significantly less flank, abdominal, urethral pain and hematuria scores (all p 

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  • Cardiovascular safety in refractory incontinent patients with overactive bladder receiving add-on mirabegron therapy to Solifenacin (BESIDE)
    International journal of clinical practice, 2017
    Co-Authors: Marcus J Drake, Christopher R Chapple, Adil Esen, Stavros Athanasiou, David Mitcheson, Sender Herschorn, Emad Siddiqui, Scott Macdiarmid, Javier Cambronero Santos, Moses Huang
    Abstract:

    © 2017 John Wiley & Sons Ltd.Summary : Aims/objectives: : In the BESIDE study, combination therapy (antimuscarinic [Solifenacin] and β3-adrenoceptor agonist [mirabegron]) improved efficacy over Solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder (OAB) patients; however, a potential synergistic effect on the cardiovascular (CV) system requires investigation. Methods: OAB patients remaining incontinent despite daily Solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (Solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), Solifenacin 5 or 10 mg for 12 weeks. CV safety assessments included frequency of CV-related treatment-emergent adverse events (TEAEs), change from baseline in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and electrocardiogram (ECG) parameters. Results: The frequency of hypertension, tachycardia and ECG QT prolongation, respectively, was low and comparable across combination (1.1%, 0.3%, 0.1%), Solifenacin 5 mg (0.7%, 0.1%, 0.1%), and Solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination (0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), Solifenacin 5 mg (-0.93 mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and Solifenacin 10 mg (-1.28 mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and Solifenacin monotherapy; SBP was unchanged with combination and decreased with Solifenacin monotherapy. Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups, except for QT interval corrected using Fridericia's formula, which was higher with Solifenacin 10 mg (3.30 mseconds) vs. combination (0.49 mseconds) and Solifenacin 5 mg (0.77 mseconds). Conclusion: The comparable frequency of CV-related TEAEs, changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and Solifenacin are combined.

  • efficacy and safety of mirabegron add on therapy to Solifenacin in incontinent overactive bladder patients with an inadequate response to initial 4 week Solifenacin monotherapy a randomised double blind multicentre phase 3b study beside
    European Urology, 2016
    Co-Authors: Marcus J Drake, Christopher R Chapple, Adil Esen, Stavros Athanasiou, Javier Cambronero, David Mitcheson, Sender Herschorn, Tahir Saleem, Moses Huang, Emad Siddiqui
    Abstract:

    Background Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy. Objective To evaluate the efficacy and the safety and tolerability of combination (Solifenacin 5mg and mirabegron 50mg) versus Solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of Solifenacin 5mg. Design, setting, and participants OAB patients remaining incontinent despite daily Solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or Solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4. Outcome measurements and statistical analysis The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (Solifenacin plus mirabegron) with one treatment alone (Solifenacin) tested the superiority of combination versus Solifenacin 5mg, noninferiority (and potential superiority) of combination versus Solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus Solifenacin monotherapy. Results and limitations A total of 2174 patients were randomised to combination (n=727), Solifenacin 5mg (n=728), or Solifenacin 10mg (n=719). At EOT, combination was superior to Solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p Conclusions Adding mirabegron 50mg to Solifenacin 5mg further improved OAB symptoms versus Solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial Solifenacin 5mg. Patient summary In this 12-wk study, overactive bladder patients who remained incontinent despite initial Solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with Solifenacin 5mg was superior to Solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated. Trial registration ClinicalTrials.gov NCT01908829.

  • combination therapy with Solifenacin and tamsulosin oral controlled absorption system in a single tablet for lower urinary tract symptoms in men efficacy and safety results from the randomised controlled neptune trial
    European Urology, 2013
    Co-Authors: Philip Van Kerrebroeck, Christopher R Chapple, T. Drogendijk, Monique Klaver, Roman Sokol, Mark Speakman, Klaudia Traudtner, Marcus J Drake
    Abstract:

    Abstract Background Storage symptoms are particularly bothersome in men with lower urinary tract symptoms (LUTS) but may not be adequately treated by α-blocker monotherapy. Objective To assess the efficacy and safety of a fixed-dose combination (FDC) of Solifenacin and an oral controlled absorption system (OCAS) formulation of tamsulosin compared with placebo and compared with tamsulosin OCAS (TOCAS) monotherapy in men with moderate to severe storage symptoms and voiding symptoms. Design, setting, and participants A double-blind 12-wk phase 3 study in 1334 men with storage and voiding LUTS: total International Prostate Symptom Score (IPSS) ≥13, maximum urinary flow rate (Q max ) 4.0–12.0ml/s, two or more urgency episodes per 24 h of Patient Perception of Intensity of Urgency Scale grade 3 or 4, and eight or more micturitions per 24h. Intervention Patients were randomised to placebo, TOCAS 0.4mg, FDC Solifenacin 6mg plus TOCAS 0.4mg, or FDC Solifenacin 9mg plus TOCAS 0.4mg. Outcome measurements and statistical analysis Primary efficacy end points were (1) total IPSS and (2) Total Urgency and Frequency Score (TUFS). An FDC met the success criteria if it demonstrated superiority compared with placebo and noninferiority compared with TOCAS for total IPSS, as well as superiority compared with TOCAS for TUFS. Results and limitations Reductions in total IPSS and TUFS were observed with both Solifenacin 6mg plus TOCAS (−7.0 and −8.1, respectively) and Solifenacin 9mg plus TOCAS (−6.5 and −7.6, respectively) compared with TOCAS (−6.2 and −6.7, respectively) and placebo (−5.4 and −4.4, respectively). Solifenacin 6mg plus TOCAS met all prespecified success criteria for both primary end points, while Solifenacin 9mg plus TOCAS met success criteria compared with placebo but not compared with TOCAS. Both FDCs improved quality of life (QoL) measures and were well tolerated, with low incidences of acute urinary retention. Conclusions The FDC of Solifenacin 6mg plus TOCAS significantly improved storage and voiding symptoms, as well as QoL parameters, compared with placebo. This FDC also improved storage symptoms and QoL compared with TOCAS alone in men with moderate to severe storage symptoms and voiding symptoms, and it was well tolerated. Trial registration ClinicalTrials.gov Identifier: NCT01018511).