Topical Pirenzepine for Diabetic Neuropathy

Overseen By Carolina Casellini, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: WinSanTor, Inc

Must not be taking: Anticholinergics, Antispasmodics

Disqualifiers: Severe neuropathy, Proliferative retinopathy, Dialysis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new topical treatment, pirenzepine (a medication applied to the skin), can alleviate painful peripheral neuropathy in individuals with Type 2 Diabetes. Participants will apply either the active treatment or a placebo (a solution without the active ingredient) to their calves, ankles, and feet daily for 12 weeks. The trial aims to determine if the treatment can reduce pain and discomfort. Individuals who have experienced painful peripheral neuropathy in their lower legs for at least a year and have stable diabetes and pain management plans might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications. However, you must be on stable diabetic and pain treatments before and during the study, and certain topical pain treatments are not allowed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that topical pirenzepine is generally well-tolerated. In past studies, researchers carefully monitored participants' heart rate and blood pressure to ensure safety. The results revealed no major changes or serious safety issues, suggesting the treatment is safe for most people. However, like any medication, some might experience minor side effects. Always consult a healthcare provider to make the best choice for your health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for painful peripheral neuropathy in type 2 diabetes, which often include oral medications like gabapentin or duloxetine, pirenzepine offers a unique approach as a topical solution. This treatment is exciting because it targets the affected areas directly, potentially reducing systemic side effects common with oral medications. Additionally, pirenzepine's mechanism involves modulating the muscarinic receptors, offering a new pathway to manage nerve pain as opposed to the traditional methods that often focus on neurotransmitter modulation. Researchers are hopeful that this targeted, topical approach will provide more effective and safer pain relief for patients.

What evidence suggests that this treatment might be an effective treatment for Type II Diabetes with painful peripheral neuropathy?

Research has shown that pirenzepine might alleviate painful nerve damage in people with diabetes. Studies have found that applying pirenzepine to the skin can promote nerve growth and protect against damage. In several animal studies, blocking certain nerve effects with pirenzepine led to nerve protection and growth. Early results also suggest that this treatment can reduce pain from nerve damage. Over time, applying pirenzepine to the skin has shown promise in helping nerves damaged by neuropathy to regrow. Participants in this trial will receive either the WST-057 active topical solution containing pirenzepine or a placebo solution, both applied once daily for 12 weeks. ^{1 6 7 8 9}

Who Is on the Research Team?

Angela Hansen

Principal Investigator

WinSanTor, Inc

Are You a Good Fit for This Trial?

Inclusion Criteria

Men must use a contraceptive that is accepted by both of us, such as a condom with a diaphragm, a condom with a cervical cap, or a condom with spermicide.

Be able to report accurately and reliably symptoms, including treatment-emergent signs and symptoms.

The individual has had diabetic neuropathy for at least 12 months that has affected their lower extremities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline/Day 0

Initial assessments and baseline measurements are conducted

1 day

1 visit (in-person)

Treatment

Participants receive either the active topical solution or placebo once daily for 12 weeks

12 weeks

4 visits (in-person), 2 visits (phone assessment)

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (phone assessment)

What Are the Treatments Tested in This Trial?

Interventions

• Pirenzepine

How Is the Trial Designed?

Group I: WST-057 active: 4 mL of WST-057 (4%; 146 mg of pirenzepine free base monohydrate) topical solution Experimental Treatment 1 Intervention

The WST-057 is the active topical solution and contains pirenzepine free base monohydrate. It is dispensed with a pump to deliver (with 4 pumps) 4 mL to the calves (mid-calf sock line), ankles and the tops of both feet. Both solutions (active and placebo) are applied once-a-day for 12 weeks.

Group II: Placebo: 4 mL of matching placebo topical solution. Placebo Group 2 Interventions

The placebo solution contains the same ingredients as the active solution with the exception of the active WST-057. It is dispensed with a pump to deliver 4 mL to the calves (mid-calf sock line), ankles and the tops of both feet. Both solutions (active and placebo) are applied once-a-day for 12 weeks.

Who Is Running the Clinical Trial?

WinSanTor, Inc

Lead Sponsor

Trials

4

Recruited

190+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Eastern Virginia Medical School

Collaborator

Trials

77

Recruited

16,500+

Published Research Related to This Trial

MetaADEDB 2.0 is an updated online database that now includes 744,709 drug-adverse drug event (ADE) associations, representing a 40% increase from its previous version, making it a more comprehensive resource for researchers.

The new version features a user-friendly web interface, enhancing accessibility for drug safety assessments and studies in drug discovery and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. Yu, Z., Wu, Z., Li, W., et al.[2021]

In a safety analysis of the CHIMES study involving 1,087 stroke patients, those treated with MLC601 experienced significantly fewer serious adverse events (SAEs) compared to those receiving a placebo, particularly for patients with multiple SAEs (6.7% vs. 29.3%).

Patients on MLC601 also had a significantly lower rate of prolonged hospitalizations, suggesting that MLC601 not only reduces SAEs but may also lessen the overall healthcare burden and associated medical costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency and Clinical Impact of Serious Adverse Events on Post-Stroke Recovery with NeuroAiD (MLC601) versus Placebo: The CHInese Medicine Neuroaid Efficacy on Stroke Recovery Study. Venketasubramanian, N., Moorakonda, RB., Lu, Q., et al.[2020]

The web-based adverse event tracking system (eAETS) has effectively supported 175 clinical protocols over four years, capturing 2,440 adverse event reports, including minor symptoms that could indicate serious issues.

Out of the reported AEs, 1,053 did not align with the initial risk profiles, leading to corrective recommendations in 13% of the protocols, highlighting the system's role in enhancing subject safety by identifying unanticipated patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of minor adverse event tracking on subject safety: a web-based system. Shenvi, NV., Gebhart, SS.[2009]

The SMART Safety dataset is the largest collection of empirical data on adverse events in healthcare, comprising 151 systematic reviews and 629 meta-analyses, which enhances the understanding of safety outcomes in randomized controlled trials.

This dataset, which includes over 2,300 trials and 362 harm outcomes, has been rigorously validated to ensure high data quality, providing a valuable resource for addressing rare adverse events and biases in evidence synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SMART Safety: An empirical dataset for evidence synthesis of adverse events. Fan, S., Yu, T., Yang, X., et al.[2023]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04005287?cond=%22Peripheral%20Nervous%20System%20Disease%22&intr=%22Anti-Ulcer%20Agents%22&viewType=Table&rank=2

A 24-Week Study of Topical Pirenzepine or Placebo in ...

An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

2.

reports.mountsinai.org

reports.mountsinai.org/article/neuro2022-07-peripheral-neuropathy-in-diabetes-robinson-papp-and-george

Clinical Trials To Study Two Agents For Painful Peripheral ...

The primary outcome is pain, but a secondary outcome is treatment of the underlying disease process. “There are preliminary data for this therapeutic agent that ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05488873

NCT05488873 | A Study of Topical Pirenzepine or Placebo ...

This is a randomized, double-blind, placebo-controlled adaptive study of the safety, tolerability, and exploratory efficacy of once-daily topical WST-057 ...

4.

reporter.nih.gov

reporter.nih.gov/project-details/10161766

Clinical Studies

Removal of this cholinergic “brake” by muscarinic antagonists promotes nerve growth and protects against neuropathy in multiple animal models of diabetes, ...

5.

pfsfoundation.org

pfsfoundation.org/news/biotech-firm-with-promising-treatment-for-peripheral-nerve-damage-soliciting-input-from-pfs-patients/

Biotech Firm with Promising Treatment for Peripheral ...

Over the past decade, the WinSanTor team has demonstrated that topically administered pirenzepine can regrow peripheral nerves damaged by ...

6.

cdn.caymanchem.com

cdn.caymanchem.com/cdn/msds/29527m.pdf

Safety Data Sheet

29868-97-1 Pirenzepine (hydrochloride). · Identification number(s) ... Indication of any immediate medical attention and special treatment needed.

7.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT05488873/a-study-of-topical-pirenzepine-or-placebo-in-oncology-patients-with-chemotherapy-induced-peripheral-neuropathy

A Study of Topical Pirenzepine or Placebo in Oncology ...

A Data Safety Monitoring Committee will review the safety data for all patients upon the completion of the first 10 patients. An interim ...

8.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03939

A Study of Topical Pirenzepine or Placebo in Oncology ...

This is a randomized, double-blind, placebo-controlled adaptive study of the safety, tolerability, and exploratory efficacy of once-daily topical WST-057

9.

withpower.com

withpower.com/trial/phase-3-pain-10-2020-7393a

A 12-Week Study of Topical Pirenzepine or Placebo in ...

The provided research articles do not contain specific safety data for Pirenzepine or its use in clinical trials. How does the drug pirenzepine differ from ...