Heather Thomas

Efficacy and safety of oxybutynin chloride topical gel for overactive bladder: a randomized, double-blind, placebo controlled, multicenter study.

PURPOSE We assessed the efficacy and safety of oxybutynin chloride topical gel vs placebo in adults with overactive bladder. MATERIALS AND METHODS Men and women 18 years or older with urge predominant urinary incontinence were enrolled in randomized, parallel group, double-blind, placebo controlled Study OG05009 done at 76 clinics in the United States. Eligible patients were assigned to receive 1 gm oxybutynin chloride topical gel (10% weight per weight ethanol based formulation of oxybutynin) or matching placebo once daily for 12 weeks. Efficacy was assessed using data from 3-day urinary diaries and the primary outcome was the change from baseline in the number of urge incontinence episodes. Safety was monitored through adverse event reporting. Efficacy results in the oxybutynin chloride topical gel and placebo groups were compared by ANCOVA with last observations carried forward. RESULTS A total of 789 randomized patients, including 704 women (89.2%), with a mean age of 59 years were assigned to treatment with oxybutynin chloride topical gel (389) or placebo (400). The mean number of urge incontinence episodes decreased significantly more in patients treated with oxybutynin chloride topical gel than in those given placebo (-3.0 vs -2.5 per day, p <0.0001). Mean urinary frequency decreased (-2.7 per day, p = 0.0017) and voided volume increased (21.0 ml, p = 0.0018) significantly more in the oxybutynin chloride group than in the placebo group (-2.0 per day and 3.8 ml, respectively). Treatment related dry mouth was more frequent in the oxybutynin chloride group than in the placebo group (27 of 389 patients or 6.9% vs 11 of 400 or 2.8%). Application site reactions were infrequently observed in the oxybutynin chloride and placebo groups (21 of 389 patients or 5.4% and 4 of 400 or 1.0%, respectively). No serious treatment related adverse events occurred. CONCLUSIONS Oxybutynin chloride topical gel was efficacious in improving overactive bladder symptoms and was well tolerated in adult patients.

Silodosin for Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Results of a Phase II Multicenter, Double-Blind, Placebo Controlled Study

PURPOSE We evaluated the efficacy and safety of 2 doses of silodosin vs placebo in men with moderate to severe abacterial chronic prostatitis/chronic pelvic pain syndrome who had not been treated previously with α-blockers for chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS In this multicenter, randomized, double-blind, phase II study, men 18 years old or older with chronic prostatitis/chronic pelvic pain syndrome, a total National Institutes of Health Chronic Prostatitis Symptom Index score of 15 or greater and a National Institutes of Health Chronic Prostatitis Symptom Index pain score of 8 or greater received 4 or 8 mg silodosin, or placebo once daily for 12 weeks. The primary efficacy end point was change from baseline to week 12 in National Institutes of Health Chronic Prostatitis Symptom Index total score. RESULTS Of 151 patients (mean age 48 years) 52 received 4 mg silodosin, 45 received 8 mg silodosin and 54 received placebo. Silodosin 4 mg was associated with a significant decrease in total National Institutes of Health Chronic Prostatitis Symptom Index score (mean ± SD change -12.1 ± 9.3) vs placebo (-8.5 ± 7.2, p = 0.0224), including a decrease in urinary symptom (-2.2 ± 2.7, placebo -1.3 ± 3.0, p = 0.0102) and quality of life (-4.1 ± 3.1, placebo -2.7 ± 2.5, p = 0.0099) subscores. The 4 mg dose of silodosin also significantly increased Medical Outcomes Study Short Form 12 physical component scores (4.2 ± 8.1, placebo 1.7 ± 9.0, p = 0.0492). During global response assessment 56% of patients receiving 4 mg silodosin vs 29% receiving placebo reported moderate or marked improvement (p = 0.0069). Increasing the dose of silodosin to 8 mg resulted in no incremental treatment effects. CONCLUSIONS Silodosin 4 mg relieved symptoms and improved quality of life in men with chronic prostatitis/chronic pelvic pain syndrome but its efficacy requires confirmation in additional studies.

Second Multicenter, Randomized, Double-blind, Parallel-group Evaluation of Effectiveness and Safety of Intravesical Sodium Chondroitin Sulfate Compared With Inactive Vehicle Control in Subjects With Interstitial Cystitis/Bladder Pain Syndrome

OBJECTIVE To gain additional safety and effectiveness information regarding intravesical 2% chondroitin sulfate in subjects with interstitial cystitis/bladder pain syndrome (IC/BPS) in a controlled clinical trial. METHODS Women with IC/BPS were randomized to receive either 8 weekly bladder instillations of 20 mL of 2% chondroitin sulfate or 20 mL of inactive control solution. The primary effectiveness endpoint was the number of positive results using the Global Response Assessment at week 11 (4 weeks after the last instillation). The secondary effectiveness endpoint was a positive response to the Interstitial Cystitis Symptom Index (ICSI) at week 11. Additional effectiveness endpoints were changes from baseline at week 11 in the total ICSI score voiding diary, and visual analog scale for pain. RESULTS A total of 98 eligible women with a diagnosis of IC/BPS met the inclusion criteria and were the intention to treat population. Of the 98 women, 83% completed the study. More patients in the chondroitin sulfate group (38.0%) reported moderate or marked improvement (considered responders) compared with the inactive control group (31.3%) at the 11-week endpoint visit. Similarly, more subjects in the active treatment group were classified as ICSI and VAS pain responders and reported a greater decrease in ICSI and VAS pain scores than the control group. None of these differences were statistically significant. CONCLUSION Intravesical chondroitin sulfate therapy for IC/BPS might result in minor improvements in IC/BPS-related symptom and pain. However, the magnitude of benefit in our small pilot study does not support its use as monotherapy for this condition. Better strategies for selecting patients with a bladder-specific clinical phenotype might improve the overall response to this type of intravesical therapy.

Efficacy and safety of oxybutynin topical gel 3% in patients with urgency and/or mixed urinary incontinence: a randomized, double-blind, placebo-controlled study.

To assess the efficacy and safety of oxybutynin transdermal gel 3% (OTG3%), with propylene glycol for enhanced skin permeation, in patients with urinary incontinence (UI).

Efficacy and safety of oxybutynin chloride topical gel for women with overactive bladder syndrome.

OBJECTIVE This subgroup analysis of a phase-3 study evaluated the efficacy and safety of oxybutynin chloride topical gel (OTG) in women with overactive bladder syndrome (OAB). STUDY DESIGN Women (n = 704) with urgency-predominant urinary incontinence received OTG or placebo for 12 weeks. The primary endpoint was change from baseline to last observation in number of daily incontinence episodes. Treatments were compared with the use of analysis of covariance. RESULTS OTG significantly reduced the number (mean ± standard deviation) of daily incontinence episodes (OTG, -3.0 ± 2.8 episodes; placebo, -2.5 ± 3.0 episodes; P < .0001), reduced urinary frequency (P = .0013), increased voided volume (P = .0006), and improved select health-related quality-of-life domains (P ≤ .0161) vs placebo. Dry mouth was the only drug-related adverse event significantly more common with OTG (7.4%) than with placebo (2.8%; P = .0062). CONCLUSION OTG was well tolerated and provided significant improvement in urinary symptoms and health-related quality of life in women with OAB.

Pharmacokinetics of Oxybutynin Chloride Topical Gel

AbstractBackground: Oxybutynin chloride topical gel (OTG; Gelnique®) is an approved formulation for the transdermal administration of oxybutynin, an established antimuscarinic therapy for overactive bladder (OAB). Transdermal administration of oxybutynin minimizes plasma concentrations of the active metabolite N-desethyloxybutynin (N-DEO), which can have anticholinergic adverse effects. Objectives: In four phase I studies, we separately assessed the effects of OTG application site selection on oxybutynin bioavailability (site-to-site study); the effects of post-application showering on oxybutynin steady-state pharmacokinetics (showering study); the effects of sunscreen application on oxybutynin absorption (sunscreen study); and the person-to-person transfer of oxybutynin through skin-to-skin contact at the application site (transference study). Methods: All four studies were open-label, randomized, phase I studies. The site-to-site and showering studies involved repeated administration of OTG to establish steady-state plasma concentrations of oxybutynin and N-DEO; the other two studies involved single doses. Clinical visits were required for pharmacokinetic sampling, supervision of OTG self-application on pharmacokinetic sampling days, showering, sunscreen application and transference experiments. The study included healthy subjects aged 18–45 years. Subjects with conditions requiring medical therapy or interfering with the application of OTG or the interpretation of pharmacokinetic results were excluded. Participants applied OTG (1 g containing oxybutynin chloride 10%, 1.14 m L/dose) once daily to the abdomen, upper arm/shoulder or thigh. Showering occurred 1–6 hours after dosing. Sunscreen was applied 30 minutes before or after OTG application. Abdomen-to-abdomen contact with movement for 15 minutes between treated and untreated participants was conducted 1 hour after dosing. Time points of serial blood sampling for pharmacokinetic analyses varied among studies. Plasma concentrations of oxybutynin and N-DEO (except transference study) were measured. Bioequivalence was tested with ANOVA models for loge-transformed plasma exposure (area under the plasma concentration-time curve [AUC]) and maximum plasma concentration (Cmax) to generate 90% confidence intervals (CIs). Results: Oxybutynin and N-DEO exposures (AUCs) from time zero to 24 hours (AUC24) were similar for the three application sites, with N-DEO/ oxybutynin mean AUC24 ratios of approximately 0.9. The 90% CIs for thigh-to-abdomen ratios of oxybutynin AUC24 (0.93, 1.23) and Cmax(0.85, 1.16) were within the interval required for bioequivalence (0.8, 1.25); the other application site ratios for oxybutynin had boundaries slightly outside this interval. Showering 1–6 hours and sunscreen application 30 minutes before or after OTG application had minor effects on oxybutynin concentrations. After vigorous skin contact between treated and untreated participants at the application site, the mean± SD AUC from time zero to 48 hours (AUC48) of oxybutynin in 12 untreated participants was 29.8 ± 24.5 ng · h/mL, approximately one-quarter of the exposures generally seen in subjects treated with a single dose of OTG. Oxybutynin AUC48 after clothing-to-skin contact was undetectable in 12 of 14 untreated participants and very low (mean ± SD 0.4 ± 0.8 ng · h/mL) in two untreated female participants. Conclusion: The bioavailability of oxybutynin and its pharmacokinetic profile are not greatly affected by application site selection, post-application showering or sunscreen use shortly before or after dosing with OTG. Oxybutynin transference to untreated persons is essentially prevented by avoiding direct skin-to-skin contact with the application site.

EFFICACY AND SAFETY OF OXYBUTYNIN CHLORIDE TOPICAL GEL IN WOMEN WITH OVERACTIVE BLADDER: A RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY

INTRODUCTION AND OBJECTIVES: Oxybutynin chloride topical gel (OTG) is a new 10% w/w ethanolic transdermal formulation of oxybutynin. The efficacy and safety of OTG vs placebo were assessed in a randomized, parallel-group, double-blind, placebo-controlled study (OG05009; 00350636 at ClinicalTrials.gov; conducted June 2006 to May 2007) in adults with overactive bladder (OAB). We report findings for the cohort of female participants. METHODS: Men and women 18 years of age with OAB and urge urinary incontinence (UI) were enrolled at 76 clinics of various types. Patients were randomized 1:1 to treatment with 1 g OTG or placebo applied once daily to rotating sites on the abdomen, upper arm/shoulder, and thigh for 12 weeks. The primary efficacy variable was change from baseline to study end (week 12 or last observation carried forward) in the mean number of daily UI episodes as recorded in a 3-day bladder diary. Analysis of covariance was used to compare efficacy results for the OTG and placebo groups. Adverse events (AEs) were monitored throughout the study. RESULTS: All randomized patients (N=789) were included in the efficacy and safety analyses; 352 patients in each treatment group were female. Mean age of female patients was 59 years; 610/704 (87%) were white. OTG treatment in women resulted in significantly greater improvements than did placebo in mean change in daily incontinence episodes and in the secondary outcome variables of daily urinary frequency and urinary voided volume (Table). At study end, complete urinary continence was achieved by 27.0% (95/352) of women treated with OTG vs 15.6% (55/352) treated with placebo. Dry mouth was the most frequent treatment-related anticholinergic AE and occurred more often with OTG (7.4%, 26/352) than with placebo (2.8%, 10/352); no patient withdrew because of dry mouth. Pruritus was the most frequent application site reaction (ASR) and occurred in 2.3% (8/352) of women treated with OTG and 0.9% of those (3/352) treated with placebo. Two women treated with OTG and 1 treated with placebo withdrew primarily because of ASRs. No serious treatment-related AEs occurred. CONCLUSIONS: OTG was well tolerated and effective at improving OAB symptoms in women with OAB and urge UI.

Effects of Oxybutynin Chloride Topical Gel on Health-Related Quality of Life in Adults with Overactive Bladder: A Randomized, Double-Blind, Placebo-Controlled Study

Objective: Oxybutynin chloride topical gel (OTG) significantly improved overactive bladder (OAB)–related urinary symptoms and was well tolerated in a phase III double-blind, placebo-controlled trial (ClinicalTrials.gov identifier NCT00350636). This study further evaluated the effect of OTG on health-related quality of life (HRQoL) in adults with OAB. Methods: Adults aged 18 years or older with urge-predominant urinary incontinence were assigned randomly to OTG 1 g/day or matching placebo for 12 weeks. HRQoL was measured by the Incontinence Impact Questionnaire (IIQ) and the King’s Health Questionnaire (KHQ) at baseline and at weeks 1, 4, 8, and 12. Between-group differences in IIQ or KHQ score changes from baseline to week 12 or last observation were compared by analysis of covariance. Results: Of 789 study participants (704 women, 85 men), 389 received OTG and 400 received placebo. Mean age was 59 ± 12 years. IIQ total score improved significantly more in participants treated with OTG (P = 0.0005) than in those treated with placebo, as did scores on all four IIQ subscales: Emotional Health (P = 0.0002), Social Relationships (P = 0.0019), Travel (P = 0.0068), and Physical Activity (P = 0.0078). KHQ scores improved significantly more with OTG than with placebo in the more incontinence-specific domains: Incontinence Impact (P = 0.0023), Symptom Severity (P = 0.0024), Severity (Coping) Measures (P = 0.0058), Sleep/Energy (P = 0.0061), Role Limitations (P = 0.0133), and Personal Relationships (P = 0.0489). Conclusion: Treatment with OTG resulted in significant HRQoL improvements in adults with OAB.

Effect of baseline symptom severity on continence improvement mediated by oxybutynin chloride topical gel

Background In a recent placebo-controlled Phase III study, oxybutynin chloride topical gel (OTG) significantly improved urinary continence in patients with overactive bladder. In this post hoc analysis, the effect of incontinence severity on OTG-mediated improvement in continence was evaluated. Methods Change from baseline in the number of incontinence episodes was evaluated in patients with two to three incontinence episodes/day (moderate incontinence) and those with more than three incontinence episodes/day (severe incontinence). Results In patients with moderate (n = 171) and severe (n = 556) incontinence, reduction in incontinence episodes (mean ± standard deviation) was greater (P < 0.01) with OTG (moderate, −1.7 ± 1.4; severe, −3.6 ± 3.0) than with placebo (moderate, −1.2 ± 1.3; severe, −3.1 ± 3.4). Continence achievement rate with OTG was 48.2% (placebo, 24.4%) among patients with moderate incontinence and 17.8% (placebo, 12.1%) among those with severe incontinence. Conclusion Absolute placebo-adjusted reduction in incontinence episodes with OTG was not affected by baseline incontinence severity. Continence achievement was more likely if symptoms were less severe.