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.
Overactive bladder syndrome (OAB) is defined by the International Urogynecological Association and the International Continence Society as urinary urgency, usually accompanied by increased frequency and nocturia, with or without urgency urinary incontinence (UUI), in the absence of urinary tract infection or other obvious pathologic condition. OAB prevalence in women has been estimated at 12.8% in Europe and Canada (EPIC study) and 16.9% in the United States (National Overactive Bladder Evaluation [NOBLE] study). OAB has a significant negative effect on health-related quality of life (HRQoL) in women, as measured by the Incontinence Impact Questionnaire (IIQ) and the King’s Health Questionnaire (KHQ). OAB was shown to affect all 4 IIQ domains in women, including mobility (travel), physical activity, social relationships, and emotional health. In a community-based 6-month open-label study of mostly female patients with OAB, the KHQ domains that received the highest scores (which indicated the greatest HRQoL impairment) were incontinence impact, symptom severity, sleep/energy, severity (coping) measures, physical limitations, and role limitations.
OAB often is accompanied by urinary incontinence, particularly UUI. In the EPIC study, approximately 50% of women with OAB experienced urinary incontinence. In the United States, OAB with UUI is far more common among women (9.3%) than men (2.6%), and women with UUI tend to be younger than men with UUI. OAB and urinary incontinence interfere with daily activities and may reduce work productivity, limit social interaction, and impair sexual function. UUI also was shown to be associated with increased rates of depression in women.
Oxybutynin is a well-established antimuscarinic therapy for patients with OAB. A drawback of oral oxybutynin formulations is their association with anticholinergic adverse effects, such as constipation, blurred vision, dizziness, and dry mouth. These adverse effects have been attributed to presystemic metabolism of oxybutynin in the liver and gut and largely can be avoided by transdermal application of oxybutynin. Oxybutynin transdermal system, which uses a patch delivery system, was shown to improve urinary symptoms and HRQoL in patients with OAB and to have few anticholinergic adverse effects. However, the patch delivery system appears to have the propensity to cause application-site skin reactions in some patients.
Oxybutynin chloride topical gel (OTG) is a novel gel-based formulation of 10% oxybutynin. Once-daily application of OTG results in a pharmacokinetic profile similar to that of therapeutic doses of the oxybutynin transdermal system. In a recent phase-3 study in patients with urgency or mixed urinary incontinence, OTG provided significant improvement in urinary symptoms that included significant reductions in the numbers of daily incontinence episodes and micturitions. In addition, OTG was associated with low incidences of anticholinergic adverse events and application-site skin reactions. In this subgroup analysis, we evaluated the efficacy and safety of OTG in female participants in the phase-3 study and included the effects of OTG on HRQoL.
Materials and Methods
Patients and treatment
The design and main results of the OTG phase-3 study (OG05009; ClinicalTrials.gov identifier NCT00350636 ) have been published. Briefly, participants in this randomized, placebo-controlled, double-blind study were men and women ≥18 years old with UUI or urgency-predominant urinary incontinence, an average of ≥8 urinary and ≥4 UUI episodes per day as recorded in a 3-day urinary diary, a mean voided volume ≤350 mL, and a mean postvoid residual volume ≤250 mL. Eligible female patients had to be nonpregnant and nonlactating. During the 12-week study, patients received 1 g OTG or placebo gel once daily. The gel was applied to rotating sites on the abdomen, upper arms/shoulders, and thighs.
Assessment and analysis
In this subgroup analysis, efficacy was evaluated in all randomly assigned women who received at least 1 dose of OTG or placebo and provided data for the efficacy variable at baseline. The primary endpoint was change in the number of daily incontinence episodes from baseline to week 12. Secondary efficacy endpoints included change from baseline to week 12 in urinary frequency, voided volume, number of nocturia events, and IIQ and KHQ scores. An additional secondary endpoint was the percentage of patients who achieved continence. The last-observation-carried-forward method was used to impute data that were missing at week 12. The statistical significance of differences in efficacy between treatments was assessed by analysis of covariance.
Safety in all female patients who received at least 1 dose of study medication was evaluated through the recording of patient-reported adverse events, assessment of skin tolerability and vital signs, physical examination, clinical laboratory and pregnancy tests (for women of childbearing potential only), electrocardiograms, and postvoid residual volume urine volume measurement. Incidences of adverse events were compared by χ 2 or Fisher’s exact test. Baseline characteristics for efficacy variables were compared with the use of a 2-sample t test.
Results
Patients
Of the 704 female study participants in the OTG phase-3 study, those women who received OTG (n = 352) and those women who received placebo (n = 352) had similar baseline characteristics ( Table 1 ). Most patients were white (86.6%); mean age was 59 years, and mean body mass index was 31 kg/m 2 ( Table 1 ). Overall discontinuation rates were similar for OTG (10.5%) and placebo (10.8%). Adverse events led to treatment discontinuation by <5% of women in both treatment groups.
| Characteristic | Treatment group | |
|---|---|---|
| Oxybutynin chloride topical gel | Placebo | |
| Mean age, y a | 59.2 ± 12.4 | 59.0 ± 12.2 |
| <65, n (%) | 228 (64.8) | 232 (65.9) |
| ≥65, n (%) | 124 (35.2) | 120 (34.1) |
| Mean weight, kg a | 82.3 ± 20.6 | 83.8 ± 22.5 |
| Mean height, cm a | 162.4 ± 6.8 | 162.9 ± 6.9 |
| Body mass index | ||
| Mean, kg/m 2a | 31.1 ± 7.3 | 31.6 ± 8.2 |
| <32 kg/m 2 , n (%) | 204 (58.0) | 198 (56.3) |
| ≥32 kg/m 2 , n (%) | 148 (42.0) | 151 (42.9) |
| Race, n (%) | ||
| White | 313 (88.9) | 297 (84.4) |
| Black | 30 (8.5) | 47 (13.4) |
| Asian | 5 (1.4) | 5 (1.4) |
| Other | 4 (1.1) | 3 (0.9) |
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