A 12-Week Study of Topical Pirenzepine or Placebo in Type 2 Diabetic Patients (T2DM) With Painful Peripheral Neuropathy

NCT04786340 | Completed Phase 2 FDA Drug

• 2 other identifiers: WST-PZP-0035R44DK104512
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 12 week, 2-arm, blinded, single-site, placebo-controlled Phase II study in subjects with Type II Diabetes and painful peripheral neuropathy.

Conditions

Painful Diabetic Neuropathy; Diabetes Mellitus

Keywords

Diabetes Mellitus; Type 2 DM; US; WST-057

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 patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  12 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 patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  12 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 patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  12 weeks

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

  Safety will be assessed by observing changes in patients' blood tests when compared to normal lab values/ranges after once daily dosing of 1 dose level of WST-057 solution or placebo. The number of participants with treatment-related adverse events as assessed by CTCAEv4.0 will be reported.

  12 weeks

Secondary Outcomes (5)

• Utah Early Neuropathy Score (UENS)

  12 weeks

• modified Toronto Clinical Neuropathy Score (mTCNS)

  12 weeks

• Norfolk Quality of Life- Diabetic Peripheral Neuropathy (Norfolk-QOL-DN)

  12 weeks

• Visual Analogue Score for Pain (VAS)

  12 weeks

• Neuropathy Total Symptom Score-6 (NTSS-6)

  12 weeks

Study Arms (2)

Placebo: 4 mL of matching placebo topical solution.

PLACEBO COMPARATOR

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.

Drug: Placebo: WST-057 4mL topical solution

WST-057 active: 4 mL of WST-057 (4%; 146 mg of pirenzepine free base monohydrate) topical solution

EXPERIMENTAL

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.

Drug: Active: WST-057 4mL (146 mg pirenzepine free base monohydrate) topical solution

Interventions

Active: WST-057 4mL (146 mg pirenzepine free base monohydrate) topical solution DRUG

WST-057

WST-057 active: 4 mL of WST-057 (4%; 146 mg of pirenzepine free base monohydrate) topical solution

Placebo: WST-057 4mL topical solution DRUG

Placebo

Placebo: 4 mL of matching placebo topical solution.

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 2016 American Diabetes Association guidelines).
• Male and female patients in the age range of 30 to 75 years (inclusive).
• Diagnosis of 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, including abstinence; hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or intrauterine system; or vasectomy (partner), for at least 1 month before the screening visit and for 1 month after the end of the study. 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. Eligible female subjects must also have a negative serum beta-human chorionic gonadotropin 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).
• Prior 24 hrs VAS for pain and/or altered sensations on lower extremities \> 30 mm (0 mm = no pain-100 mm = very severe pain) at screening.
• 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 top surface of 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 glycemic control with standard of care diabetic therapies (≥3 months prior to screening). This includes diet and exercise alone or in association with oral or injectable anti-diabetic drugs (monotherapy or combinations) that are not anticipated to change during the course of the study, except if medically required.
• Be on 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 (e.g. local anesthetics) or trans electrical nerve stimulation will not be permitted.
• Regular and stable use of pharmacological pain treatment (less than or equal to 30 mg morphine equivalent) for at least 8 weeks prior to screening.

You may not qualify if:

• Severe neuropathy as determined by a UENS score \> 24 at screening
• Proliferative retinopathy or maculopathy requiring acute treatment.
• Requiring dialysis.
• Impaired liver function, defined as aspartate aminotransferase or alanine aminotransferase \> 3 times the upper limit of normal.
• Presence of clinically significant peripheral or autonomic neuropathy that is clearly of nondiabetic origin.
• Prior week VAS for pain and/or altered sensations on lower extremities \< 30 mm (0 mm = no pain-100 mm = very severe pain) at screening.
• Local (topical) anesthetics or analgesics including lidocaine, capsaicin, cannabinoid (CBD) oil/products or compounded topical pharmaceutical agents.
• 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 6 months.
• Uncontrolled or untreated hypothyroidism.
• Active and/or systemic infections (e.g., HIV, hepatitis, tuberculosis, syphilis), 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.

Sponsors & Collaborators

• WinSanTor, Inc: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Eastern Virginia Medical School: collaborator

Study Sites (1)

Eastern Virginia Medical School

Norfolk, Virginia, 23510-1001, United States

Location

MeSH Terms

Conditions

Diabetic Neuropathies; Diabetes Mellitus

Interventions

Solutions

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

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: Each subject will be randomized by an Interactive Web Response System (IWRS). When a subject is randomized, the IWRS will assign a randomization number for each subject, corresponding to a specific treatment code. The randomization number will be automatically input into the electronic Case Report Form (eCRF) by the system. The corresponding treatment code will only be accessible to the unblinded personnel.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2:1 ratio, Active (4% WST-057 topical solution): Placebo (matching placebo solution)

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 8, 2021
• Study Start: November 20, 2020
• Primary Completion: December 8, 2022
• Study Completion: December 8, 2022
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)