AzTrials
AzTrials

Peripheral NeuropathyPhase 2NCT04005287

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

A Phase 2 study testing WST-057 (4% pirenzepine) Lose Dose 2mL and WST-057 (4% pirenzepine) High Dose 4mL in people with Peripheral Neuropathy and Painful Diabetic Neuropathy, run by WinSanTor, Inc at 5 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
WST-057 (4% pirenzepine) Lose Dose 2mL and WST-057 (4% pirenzepine) High Dose 4mL
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
58 participants
Where
5 sitesCanada
Study dates
15 Oct 2019to 15 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 17Show fewer
  • 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.
  • General health status must be acceptable for participation in this 24-week clinical study, with no hospitalizations for medical conditions within 12 weeks before and during screening per judgment of the Investigator. Any question regarding eligibility will be addressed with the medical monitor.
  • Fluency (oral and written) in the language in which the standardized tests will be administered.

Who cannot join

  • 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.
Show all 35Show fewer
  • 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).
  • Urinary retention or an enlarged prostate.
  • Uncontrolled glaucoma.
  • Other clinically significant, active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary, endocrine, rheumatologic or hematological system that, in the opinion of the Investigator, would compromise the subject's participation in the study, might confound the results of the study, or pose additional risk in administering the study drug.
  • New treatment with (< 3 months) antioxidant supplements, vitamins, or drugs known to affect oxidative stress and peripheral diabetic neuropathy such as Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine and Vitamin B12.
  • Known or suspected history of alcohol or substance abuse. Moderate and stable consumption of alcohol, cannabis and nicotine are not exclusionary
  • Mental incapacity, unwillingness, or language barrier precluding adequate understanding of or cooperation with the study.
  • Women of childbearing potential who are pregnant, breast-feeding, or intend to become pregnant. Women of childbearing potential must have a negative pregnancy test at Screening and must agree to use adequate contraceptive methods during the study and for 1 month after the last dose of study drug (see inclusion criterion 5).
  • History of allergy or sensitivity to M1 antagonists or anticholinergics in general or any of the components of the investigational product formulations.
  • Known allergy or hypersensitivity to pirenzepine or another component of the investigational product.
  • History of sensitive skin, as defined by a requirement to use soap and skin products formulated for "sensitive skin".
  • Currently taking any medicines to treat overactive bladder (anticholinergic agents, such as Gelnique).
  • Failure or inability to perform screening or baseline assessments.
  • Patients with any condition that could potentially interfere with the conduct of the study or confound efficacy evaluations, including the following as specified in numbers 29 through 35 below:
  • Pain or neuropathy from another cause (as determined by the investigator) (including central pain, radiculopathy, painful arthritis, autoimmune and inflammatory diseases including rheumatoid arthritis, lupus, Sjogren's syndrome, vasculitic disorders such as periarteritis nodosa, Churg-Strauss, etc., celiac disease, Crohn's disease, ulcerative colitis, spondyloarthropathies, sarcoidosis, etc.).
  • Skin or soft-tissue lesions in the area affected by neuropathy that are painful or could alter sensation.
  • Systemic infections (eg, HIV, hepatitis, tuberculosis, syphilis).
  • Exposure to an experimental drug, experimental biologic, or experimental medical device within 3 months before screening.
  • Any open wound(s) and/or sunburn(s) in the dosing area. Subjects who have a wound and/or sunburn at screening that is anticipated to resolve before day -1 can be enrolled.
  • History of a serious skin disease (as determined by the Investigator), such as skin cancer, psoriasis, eczema or stasis dermatitis.
  • Receipt of a tattoo in the dosing area within 12 months of dosing.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Canada5 sites

  • University of Alberta

    Edmonton, Alberta, T6G 2E1

  • McMaster University Medical Centre

    Hamilton, Ontario, L8N 3Z5

  • Ottawa Hospital Research Institute Civic Campus

    Ottawa, Ontario, K1Y 4E9

  • CRCHUS

    Sherbrooke, Quebec, J1H 5N4

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

Other trials in Canada

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel, 24-Week, Phase 2a Study of Topical Pirenzepine (WST-057) or Placebo in Type 2 Diabetic Patients With Peripheral Neuropathy

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.

Read the detailed description

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. Subjects will attend visits at screening (day -45 to -28); day 1 (baseline); weeks 2, 4, 8, 12, 16, 20, 24; and follow-up (week 26). Approximately 60 subjects with T2DM with peripheral neuropathy will be randomized to 1 of 4 treatment groups in a 1:1:4:4 ratio: placebo control 2 mL (n = 6 subjects), placebo control 4 mL (n = 6 subjects); low dose (2 mL) WST-057 (73 mg pirenzepine free base monohydrate) (n = 24 subjects); and high dose (4 mL) WST-057 (146 mg pirenzepine free base monohydrate) (n = 24 subjects), with the assumption that a total of 50 subjects will complete the study.

This study is designed with 4 periods: screening, baseline/day 1, outpatient treatment, and safety follow-up.

Being tested
WST-057 (4% pirenzepine) Lose Dose 2mL, WST-057 (4% pirenzepine) High Dose 4mL, Placebo Low Dose, Placebo High Dose
Keywords
Diabetes Mellitus
Medical subject headings
Peripheral Nervous System Diseases, Diabetic Neuropathies, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • WST-057 (4% pirenzepine) Lose Dose 2mLDrug

    Topical Solution

  • WST-057 (4% pirenzepine) High Dose 4mLDrug

    Topical Solution

  • Placebo Low DoseDrug

    Topical Solution

  • Placebo High DoseDrug

    Topical Solution

Study groups in NCT04005287
Study groupRoleWhat they receive
WST-057 Matching placebo 2 mL volumePlacebo comparatorNot described
Receives: Drug: Placebo Low Dose
WST-057 Matching placebo 4mL volumePlacebo comparatorNot described
Receives: Drug: Placebo High Dose
WST-057 (4% pirenzepine) 2mL volumeActive comparatorNot described
Receives: Drug: WST-057 (4% pirenzepine) Lose Dose 2mL
WST-057 (4% pirenzepine) 4mL volumeActive comparatorNot described
Receives: Drug: WST-057 (4% pirenzepine) High Dose 4mL

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 24 weeks

  2. 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.

    Measured: 24 weeks

  3. 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.

    Measured: 24 weeks

  4. 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.

    Measured: 24 weeks

Secondary outcomes (2)

  1. Intraepidermal Nerve Fiber Density (IENFD)

    Evaluate the efficacy of WST-057 to increase IENFD present in punch biopsies collected in the calf. The nerves will be counted in these punch biopsies and the change in the density will be measured between screening and the week 24 visit. The more nerves or a higher nerve density correlates with better sensation.

    Measured: 24 weeks

  2. Norfolk Quality of Life Measure (QOL) Patient Questionnaire

    Determine the impact of once-daily topical dosing of WST-057 on a QOL measurement. The score from the QOL questionnaire will be tabulated from each visit to determine if an improvement in the quality of life could be measured using this scale between screening and the week 24 visit.All symptoms (1-7) are scored as either a 1 or a 0, indicating a presence or absence of the symptom. With the exception of Questions 31, and 32, the other items are scored according to the 5-point Likert Scale (0-4, "No Problem" to "Severe Problem"). In Question 31, "Good", the middle item, is scored as O. "Very Good" is scored as -1, Excellent" is scored as -2. "Fair is scored as 1, and "Poor" is scored as 2. In Question 32, "About the Same", the middle item, is scored as 0. "Somewhat better" is scored as -1, "Much better" is scored as -2. "Somewhat worse" is scored as 1, and "Much worse" is scored as 2. A higher score indicates worse neuropathy-related quality of life score than a lower number.

    Measured: 24 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2019
  2. Study start15 Oct 2019
  3. Primary completion15 Dec 2021
  4. Study completion15 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04005287
Sponsor's protocol ID
WST-PZP-002
Status last verified
Dec 2022
First submitted
27 Jun 2019
Last updated
16 Dec 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 41352124

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing WST-057 (4% pirenzepine) Lose Dose 2mL and WST-057 (4% pirenzepine) High Dose 4mL in people with Peripheral Neuropathy and Painful Diabetic Neuropathy, run by WinSanTor, Inc at 5 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Treatment-Emergent Adverse Events as assessed by hematology and clinical pathology blood tests. (time frame: 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04005287, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in