A 24-Week Study of Topical Pirenzepine or Placebo in Type 2 Diabetic Patients (T2DM) With Peripheral Neuropathy

NCT04005287 | Completed Phase 2 FDA Drug

• 1 other identifier: WST-PZP-002
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 5

Brief Summary

This is a randomized outpatient, double-blind, placebo-controlled, multiple-site study of the safety, tolerability, and exploratory efficacy of topically administered WST-057 (4% pirenzepine free base monohydrate) for 24 weeks in subjects with T2DM with peripheral neuropathy.

Conditions

Peripheral Neuropathy; Painful Diabetic Neuropathy; Diabetic Neuropathies, Painful

Keywords

Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• Incidence of Treatment-Emergent Adverse Events as assessed by hematology and clinical pathology blood tests.

  Safety will be assessed by observing changes in patient's blood tests when compared to normal lab values/ranges after once daily dosing of 2 dose levels of WST-057 solution or placebo. The Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 will be reported.

  24 weeks

• Incidence of Treatment-Emergent Adverse Events as assessed by vital signs (blood pressure (diastolic and systolic mmHg), heart rate (beats per minute), respiratory rate (breaths per minute).

  Safety will be assessed by observing changes in vitals signs (from baseline) in patients after daily topical doses of either 2 dose levels of WST-057 solution or placebo. The Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 will be reported.

  24 weeks

• Incidence of Treatment-Emergent Adverse Events as assessed by ECG ( measuring P Wave, QRS complex, QT Interval)

  Safety will be assessed by observing changes in ECG parameters (from baseline) in patients after daily dosing of either 2 dose levels of WST-057 solution or placebo. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 will be reported.

  24 weeks

• Incidence and Treatment-Emergent Adverse Events as assessed by a dermal assessment (Draize score (scale 0.0 - 4.0) score of skin erythema, edema, pruritus and dryness score) of the dosing area

  Dermal safety will be assessed by observing changes in dermal scores (from baseline) in patients after daily dosing of either 2 dose levels of WST-057 solution or placebo. The Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 will be reported.

  24 weeks

Secondary Outcomes (2)

• Intraepidermal Nerve Fiber Density (IENFD)

  24 weeks

• Norfolk Quality of Life Measure (QOL) Patient Questionnaire

  24 Weeks

Other Outcomes (3)

• Quantitative Thermal Threshold (QST) Quantitative Vibration Threshold (QVT)

  24 weeks

• Pain Assessment Scale: Visual Analogue Score

  24 weeks

• Patients' Global Impression of Change

  24 weeks

Study Arms (4)

WST-057 Matching placebo 2 mL volume

PLACEBO COMPARATOR

Drug: Placebo Low Dose

WST-057 Matching placebo 4mL volume

PLACEBO COMPARATOR

Drug: Placebo High Dose

WST-057 (4% pirenzepine) 2mL volume

ACTIVE COMPARATOR

Drug: WST-057 (4% pirenzepine) Lose Dose 2mL

WST-057 (4% pirenzepine) 4mL volume

ACTIVE COMPARATOR

Drug: WST-057 (4% pirenzepine) High Dose 4mL

Interventions

WST-057 (4% pirenzepine) Lose Dose 2mL DRUG

Topical Solution

WST-057 (4% pirenzepine) 2mL volume

WST-057 (4% pirenzepine) High Dose 4mL DRUG

Topical Solution

WST-057 (4% pirenzepine) 4mL volume

Placebo Low Dose DRUG

Topical Solution

WST-057 Matching placebo 2 mL volume

Placebo High Dose DRUG

Topical Solution

WST-057 Matching placebo 4mL volume

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of T2DM (as defined by the 2013 Diabetes Canada guidelines).
• Male and female patients in the age range of 18 to 75 years (inclusive).
• Presence of definite diabetic neuropathy (as defined by the Toronto Consensus Guidelines) of at least 12 months duration in the lower extremities.
• Provide written informed consent prior to entering the study or undergoing any study procedures.
• Females should be either not of childbearing potential as a result of surgery or menopause (1 year after onset), or of childbearing potential and must be practicing a highly effective medically acceptable method of contraception (e.g. abstinence, or hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); or vasectomy (partner)) for at least 1 month before the screening visit and for 1 month after the last dose of study drug. If access or use of a highly effective medically acceptable method of contraception is not achievable, then a combination of barrier methods (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) is acceptable (e.g. male condom with diaphragm, male condom with cervical cap). Eligible female subjects must also have a negative serum beta-human chorionic gonadotropin (ß-hCG) at the screening visit.
• Males must use an acceptable form of contraception (e.g., male condom with diaphragm, male condom with cervical cap, or male condom in association with spermicide)
• Glycemic control has been optimized and has been stable for at least three months prior to randomization. Optimal glycemic control refers to the best possible diabetic control that an individual patient can attain with usual standards of care, which usually takes more than two months to establish.
• Patients must have a screening IENF density range of no less than 1 IENF/mm and no more than 10 IENF/mm.
• Participating subjects must be reliable, willing, and able to cooperate with all study procedures, including the following:
• Return for study visits on the required dates
• Be physically able to inspect calves, tops of ankles, and soles of feet for wounds, infections, or other anomalies, and be able to self-administer the investigational drug to calves and feet.
• Be able to accurately and reliably report symptoms (including treatment-emergent signs and symptoms).
• Take study drug as required by protocol.
• Be on stable antidiabetic treatment (insulin, oral agents, or lifestyle) that is not anticipated to change during the course of the study, except if medically required.
• Be on stable analgesic treatment (same medication and dose) or stable nonpharmacological pain treatment for at least 4 weeks prior to screening and remain on this stable treatment throughout the study (unless otherwise directed by a physician). Nonpharmacologic pain treatment includes the following: relaxation/hypnosis, physical or occupational therapy, counseling, etc. Episodic or periodic treatments, such as monthly injections for treatment of pain (eg, local anesthetics), will not be permitted. Topical anesthetics/analgesics such as capsaicin, topical cannabinoid (CBD) oil or extracts, lidocaine patches and compounded topical applications are also not allowed.

You may not qualify if:

• Lower leg IENFD at screening of \<1 or \>10 IENF/mm.
• Uncontrolled glycemia
• Proliferative retinopathy or maculopathy requiring acute treatment.
• Requiring dialysis.
• Impaired liver function, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal.
• Presence of clinically significant peripheral or autonomic neuropathy that is clearly of nondiabetic origin.
• Uncontrolled treated/untreated hypertension (systolic blood pressure \[BP\] ≥ 180 or diastolic BP ≥ 100 at screening).
• Amputations of lower extremities or presence of foot ulcers.
• Clinically significant active macrovascular disease, including myocardial infarction or cerebrovascular event within the past 12 months.
• Uncontrolled or untreated hypothyroidism.
• Active infection (eg, HIV, hepatitis), or a history of severe infection during the 30 days prior to screening.
• Evidence of severely immunocompromised status.
• Major surgical procedure during the 90 days prior to screening.
• Diagnosis and/or treatment of malignancy (except for basal cell or squamous cell skin cancer, in-situ carcinoma of the cervix, or in-situ prostate cancer) within the past 5 years.
• Clinically significant gastric emptying abnormality (eg, severe gastroparesis).

Sponsors & Collaborators

• WinSanTor, Inc: lead

Study Sites (5)

University of Alberta

Edmonton, Alberta, T6G 2E1, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Ottawa Hospital Research Institute Civic Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

CRCHUS

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Related Publications (1)

• Sivadasan A, Fernyhough P, Calcutt NA, Frizzi KE, Gardner K, Hansen A, Breiner A, Zochodne DW, McInnes N, Punthakee Z, Gosselin S, Perkins BA, Bril V. Topical application of the antimuscarinic pirenzepine increased lower limb nerve fibre density in a phase 2a study in type 2 patients with diabetes with peripheral neuropathy. EBioMedicine. 2026 Jan;123:106055. doi: 10.1016/j.ebiom.2025.106055. Epub 2025 Dec 5.

  PMID: 41352124 DERIVED

MeSH Terms

Conditions

Peripheral Nervous System Diseases; Diabetic Neuropathies; Diabetes Mellitus

Interventions

Pirenzepine

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Angela Hansen

  WinSanTor, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 2, 2019
• Study Start: October 15, 2019
• Primary Completion: December 15, 2021
• Study Completion: December 15, 2021
• Last Updated: December 16, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)