Oxybutynin Chloride Topical Gel Research Articles

Cognitive Effects of Oxybutynin Chloride Topical Gel in Older Healthy Subjects

Background and Objective: Oxybutynin is a common antimuscarinic therapy for overactive bladder. Transdermally administered oxybutynin chloride topical gel 10% (OTG) has a low propensity for anticholinergic adverse effects and possibly also a low risk of cognitive impairment. A randomized, double-blind, placebo- and active-controlled study evaluated the effects of OTG on cognitive and psychomotor functions in older healthy adults.

Application Drying Time for Oxybutynin Chloride Topical Gel

This study determined the median drying time for oxybutynin chloride topical gel (OTG) approved for treatment of overactive bladder was 3.1 minutes, Most participants reported positive perceptions of OTG attributes.

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

BackgroundIn 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.MethodsChange 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).ResultsIn 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.ConclusionAbsolute 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.

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

Effect of baseline symptom severity on continence improvement mediated by oxybutynin chloride topical gel Peter K Sand1, Scott A MacDiarmid2, Heather Thomas3, Kim E Caramelli3, Gary Hoel3 1University of Chicago, Pritzker School of Medicine, Chicago, IL; 2Alliance Urology Specialists, Greensboro, NC; 3Watson Laboratories, Inc., Salt Lake City, UT, USA 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 &plusmn; standard deviation) was greater (P &lt; 0.01) with OTG (moderate, -1.7 &plusmn; 1.4; severe, -3.6 &plusmn; 3.0) than with placebo (moderate, -1.2 &plusmn; 1.3; severe, -3.1 &plusmn; 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. Keywords: incontinence, overactive bladder, oxybutynin chloride topical gel, continence

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

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). 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. 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). 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

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. 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). 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 mL/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 log(e)-transformed plasma exposure (area under the plasma concentration-time curve [AUC]) and maximum plasma concentration (C(max)) to generate 90% confidence intervals (CIs). Oxybutynin and N-DEO exposures (AUCs) from time zero to 24 hours (AUC(24)) were similar for the three application sites, with N-DEO/oxybutynin mean AUC(24) ratios of approximately 0.9. The 90% CIs for thigh-to-abdomen ratios of oxybutynin AUC(24) (0.93, 1.23) and C(max) (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 (AUC(48)) 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 AUC(48) 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. 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.

Development of oxybutynin chloride topical gel for overactive bladder

Overactive bladder (OAB) is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG) is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo-controlled Phase III study.

Development of oxybutynin chloride topical gel for overactive bladder

Overactive bladder (OAB) is an age-related syndrome often associated with urinary incontinence. Symptoms of OAB, such as urgency, frequency, and nocturia, can be treated effectively with inhibitors of muscarinic acetylcholine receptors. Antimuscarinic agents promote relaxation of the detrusor muscle and may modulate afferent neuronal signals involved in the regulation of the micturition reflex. Despite the availability of an increasing number of oral antimuscarinic agents, treatment persistence among patients with OAB generally appears to be low. This may be attributed, at least in part, to the common occurrence of anticholinergic adverse effects, such as dry mouth, constipation, and dizziness. Oxybutynin is a well-established antimuscarinic agent that is available in a variety of formulations. Transdermal formulations have been developed to avoid the first-pass hepatic and gastrointestinal drug metabolism responsible for the anticholinergic adverse effects often observed with oral delivery of oxybutynin. Oxybutynin chloride topical gel (OTG) is a formulation of oxybutynin that was approved by the US Food and Drug Administration in January 2009. OTG was the result of a systematic evidence-based effort to develop a formulation that preserves the efficacy of oral oxybutynin formulations while eliminating most of their anticholinergic adverse effects. Additional emphasis was put on creating a transdermal formulation with minimal potential for application-site skin reactions. The formulation and pharmacokinetic properties of OTG are reviewed in the context of recently published efficacy and tolerability data from a large multicenter, placebo-controlled Phase III study.

Transdermal Oxybutynin: What Role in the Management of Overactive Bladder?

Overactive bladder (OAB), a bothersome condition that is frequently associated with incontinence, commonly affects middle-aged and elderly people. OAB not only has a negative effect on physical and mental well-being but also accounts for billions of dollars in health care costs and lost productivity. Although OAB can be treated effectively with muscarinic acetylcholine receptor antagonists, these agents often cause anticholinergic adverse effects, such as dry mouth and constipation, which are believed to be a major reason for low treatment persistence. Oxybutynin is an established OAB treatment that is available in oral and transdermal formulations. Oxybutynin chloride topical gel (OTG) (Gelnique®, Watson Pharmaceuticals, Corona, CA, USA.) is a new formulation that was approved by the US Food and Drug Administration in January 2009. Results of a 12-week, placebo-controlled US phase 3 study demonstrated that OTG is efficacious in patients with OAB and rarely causes anticholinergic adverse events. Only dry mouth occurred significantly more often with OTG than placebo (6.9% vs. 2.8% of patients). Furthermore, OTG showed very little propensity to cause application site skin reactions. In conclusion, the efficacy and good tolerability of OTG make it a valuable treatment option for patients with OAB.

Oxybutynin topical and transdermal formulations: An update

Oxybutynin, an antimuscarinic agent, is well established for the treatment of overactive bladder (OAB) and is the gold standard for the treatment of severe neurogenic bladder. Although oral oxybutynin is effective in relieving the urinary symptoms of OAB, medication adherence is low at least in part because of substantial anticholinergic adverse effects. The poor anticholinergic tolerability has been attributed to high circulating levels of N-desethyloxybutynin (DEO), a pharmacologically active product of presystemic metabolism of oral oxybutynin in the liver and gastrointestinal tract. Transdermal formulations of oxybutynin avoid first-pass metabolism and thereby produce lower DEO plasma concentrations. Oxybutynin chloride topical gel (OTG) (Gelnique(R), Watson Pharmaceuticals, Corona, CA, USA), a new gel-based transdermal formulation of oxybutynin, was approved by the U.S. Food and Drug Administration in January 2009. Results of a placebo-controlled U.S. phase III study demonstrated that OTG is efficacious in relieving symptoms of OAB and is associated with a low incidence of anticholinergic adverse events. Patients may find that OTG, with its excellent efficacy, convenient once-daily application and outstanding tolerability profile, is a valuable alternative to oral antimuscarinic agents for the treatment of OAB.

Efficacy and Safety of Oxybutynin Chloride Topical Gel for Overactive Bladder: A Randomized, Double-Blind, Placebo Controlled Multicenter Study

Efficacy and Safety of Oxybutynin Chloride Topical Gel for Overactive Bladder: A Randomized, Double-Blind, Placebo Controlled Multicenter Study

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

ObjectiveOxybutynin 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.MethodsAdults 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.ResultsOf 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).ConclusionTreatment with OTG resulted in significant HRQoL improvements in adults with OAB.

Oxybutynin chloride topical gel: a new formulation of an established antimuscarinic therapy for overactive bladder

Background: Oxybutynin, a cholinergic-muscarinic receptor antagonist, is established as a safe and effective pharmacological treatment for patients with overactive bladder syndrome (OAB). Oxybutynin is available in multiple immediate- and extended-release oral and two transdermal formulations. Oxybutynin chloride topical gel (OTG) (Gelnique®, Watson Pharmaceuticals, Corona, CA, USA) was approved in January 2009 by the US FDA. OTG was designed to provide consistent plasma oxybutynin levels with daily application, favorably altering the circulating N-desethyloxybutynin metabolite:oxybutynin ratio, and to utilize a biocompatible delivery system, thus minimizing both the anticholinergic adverse effects of oral formulations and the application-site skin reactions associated with other available forms of transdermal delivery. Objective/methods: This review summarizes the pharmacological properties and the clinical efficacy and safety profile of OTG based on the published literature and unpublished data provided by the manufacturer upon request. Results/conclusion: OTG represents an efficacious, safe, and convenient alternative to other oxybutynin formulations and other oral anticholinergic medications for the treatment of OAB. Future studies and broad clinical experience should confirm the promising early experience observed with this formulation.

Oxybutynin chloride topical gel for the treatment of overactive bladder

Methods: This was a prospective, randomized, doubleblind, placebo-controlled trial of 789 women (89%) and men (11%) with OAB who received 1 g of OTG or placebo gel once daily for 12 weeks. Three-day bladder diaries were administered at baseline and at 12 weeks or at last observation carried forward to assess the number of urge incontinence episodes in the treated versus placebo groups. Safety was evaluated through adverse event reporting.

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.

Efficacy and Safety of Oxybutynin Chloride Topical Gel for Overactive Bladder: A Randomized, Double-Blind, Placebo Controlled, Multicenter Study

We assessed the efficacy and safety of oxybutynin chloride topical gel vs placebo in adults with overactive bladder. 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. 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. Oxybutynin chloride topical gel was efficacious in improving overactive bladder symptoms and was well tolerated in adult patients.

A SHORT-TERM, MULTICENTER, RANDOMIZED DOUBLE-BLIND DOSE TITRATION STUDY OF THE EFFICACY AND ANTICHOLINERGIC SIDE EFFECTS OF TRANSDERMAL COMPARED TO IMMEDIATE RELEASE ORAL OXYBUTYNIN TREATMENT OF PATIENTS WITH URGE URINARY INCONTINENCE

We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence. Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system. A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema. Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.