Overactive bladder (OB) is a disease that afflicts both men and women and is driven by the aging population with a prevalence estimated as high as 39% in the US and 45% for all women over 65. OB is accompanied with a significant loss of quality of life with documented increases in falls, anxiety, and depression. The muscarinicantagonists (anticholinergics) are the primary drugs for treatment, but these agents are associated withnumerous side effects and drug-drug interactions leading to discontinuation of therapy in over 50% of patientsin 6-12 months. Furthermore, with age there is a growing concern for anticholinergic drug overload (especiallydue to drug-drug interactions) leading to additional effects such as cognition impairment and other CNS affects.Studies have shown that the pharmacodynamics efficacy of muscarinic antagonists in OB therapy is stronglyassociated with area under the concentration-time curve (AUC) and that the many side effects are related tomaximum plasma concentrations (Cmax). Oxybutynin, one of the agents with the most side effects, wasformulated as an adhesive patch, which greatly reduced cholinergic side effects due to a constant effective drugconcentration. Unfortunately, the patch had its own significant side effects, mainly serious skin irritations due tothe permeation enhancers needed for effective delivery. Given the very large population afflicted with OB, andthe many OB drugs and formulations which fail to adequately treat the disease, there remains a desperate unmetmedical need for new therapy options.Multiple advantages of microneedle transdermal delivery over other transdermal methods have beendocumented. More recently, swellable hydrogel microneedles (HMN) have been shown to be a highly efficientand painless method for increasing the skin permeation of drugs without additives, sharps, or polymericmonomers entering the circulation. We have selected Trospium Chloride (TC), the OB drug with the best efficacyand least side effects, yet plagued by poor bioavailability and high pharmacokinetic variability for delivery viaHMN. The product will be a drug-free HMN array with a TC drug reservoir to enable a tightly controlled deliveryof TC, providing efficacious AUCs with consistent plasma concentrations. This self-administered patch isdesigned to deliver TC over the course of a week, and will be the first OB treatment with both excellent efficacy,as well as high patient compliance and satisfaction.The end result of this work will be a novel, transdermal delivery approach for TC with readily translatable PK,efficacy and initial preclinical safety data, ready to complete preclinical development activities leading to theopening of an IND. We have assembled a team of expert advisors and collaborators to ensure successfulcompletion of this research plan.
Public Health Relevance Statement: Project Narrative
Urinary incontinence or overactive bladder is a disease that afflicts both men and women and is driven by the
aging population, with a prevalence estimated as high as 39% in the US population. TSRL is developing a
transdermal microneedle patch for Trospium Chloride, a drug approved for treating incontinence, with an
optimized efficacy and side effect profile. This painless, self-administered patch is designed to deliver the drug
over the course of a week, and will be the first incontinence treatment with both excellent efficacy, as well as
high patient compliance and satisfaction.
Project Terms:
