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Microneedle Delivery of Trospium Chloride Optimized for Improved Tolerance and Patient Outcomes in Overactive Bladder Disease

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HD109069-01A1
Agency Tracking Number: R43HD109069
Amount: $299,620.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NICHD
Solicitation Number: PA21-259
Timeline
Solicitation Year: 2021
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-09-19
Award End Date (Contract End Date): 2023-08-31
Small Business Information
540 AVIS DR STE A
Ann Arbor, MI 48108-7906
United States
DUNS: 156551699
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 ELKE LIPKA
 (734) 223-6862
 elipka@tsrlinc.com
Business Contact
 ELKE LIPKA
Phone: (734) 223-6862
Email: elipka@tsrlinc.com
Research Institution
N/A
Abstract

Abstract
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 muscarinic
antagonists (anticholinergics) are the primary drugs for treatment, but these agents are associated with
numerous side effects and drug-drug interactions leading to discontinuation of therapy in over 50% of patients
in 6-12 months. Furthermore, with age there is a growing concern for anticholinergic drug overload (especially
due 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 strongly
associated with area under the concentration-time curve (AUC) and that the many side effects are related to
maximum plasma concentrations (Cmax). Oxybutynin, one of the agents with the most side effects, was
formulated as an adhesive patch, which greatly reduced cholinergic side effects due to a constant effective drug
concentration. Unfortunately, the patch had its own significant side effects, mainly serious skin irritations due to
the permeation enhancers needed for effective delivery. Given the very large population afflicted with OB, and
the many OB drugs and formulations which fail to adequately treat the disease, there remains a desperate unmet
medical need for new therapy options.
Multiple advantages of microneedle transdermal delivery over other transdermal methods have been
documented. More recently, swellable hydrogel microneedles (HMN) have been shown to be a highly efficient
and painless method for increasing the skin permeation of drugs without additives, sharps, or polymeric
monomers entering the circulation. We have selected Trospium Chloride (TC), the OB drug with the best efficacy
and least side effects, yet plagued by poor bioavailability and high pharmacokinetic variability for delivery via
HMN. The product will be a drug-free HMN array with a TC drug reservoir to enable a tightly controlled delivery
of TC, providing efficacious AUCs with consistent plasma concentrations. This self-administered patch is
designed 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 the
opening of an IND. We have assembled a team of expert advisors and collaborators to ensure successful
completion of this research plan.

* Information listed above is at the time of submission. *

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