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

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ClinicalTrials.gov Identifier: NCT04005287
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : March 8, 2021
Sponsor:
Information provided by (Responsible Party):
WinSanTor, Inc

Tracking Information
First Submitted Date  ICMJE June 27, 2019
First Posted Date  ICMJE July 2, 2019
Last Update Posted Date March 8, 2021
Actual Study Start Date  ICMJE October 15, 2019
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • Incidence of Treatment-Emergent Adverse Events as assessed by hematology and clinical pathology blood tests. [ Time Frame: 24 weeks ]
    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.
  • 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). [ Time Frame: 24 weeks ]
    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.
  • Incidence of Treatment-Emergent Adverse Events as assessed by ECG ( measuring P Wave, QRS complex, QT Interval) [ Time Frame: 24 weeks ]
    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.
  • 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 [ Time Frame: 24 weeks ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 28, 2019)
Safety and Tolerability [ Time Frame: 24 weeks ]
Assessment of safety and tolerability of 2 dose levels of WST-057 solution after once-daily topical administration. Safety will be assessed using physical exams, vital signs, dermal assessments and ECGs. The Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 will be reported.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2019)
  • Intraepidermal Nerve Fiber Density (IENFD) [ Time Frame: 24 weeks ]
    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.
  • Norfolk Quality of Life Measure (QOL) Patient Questionnaire [ Time Frame: 24 Weeks ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 28, 2019)
Quantitative Thermal Threshold (QST) Quantitative Vibration Threshold (QVT) [ Time Frame: 24 weeks ]
Determine the impact of once daily dosing of WST-057 on QST and QVT. Sensory and vibration probes attached to an instrument that measures response will be applied to the feet of patients to determine if there is an improvement from the screening visit until 24 weeks post dosing. The lower the threshold for thermal and vibration sensation indicates better feeling or less neuropathy.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A 24-Week Study of Topical Pirenzepine or Placebo in Type 2 Diabetic Patients (T2DM) With Peripheral Neuropathy
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blinded
Primary Purpose: Treatment
Condition  ICMJE
  • Peripheral Neuropathy
  • Painful Diabetic Neuropathy
  • Diabetic Neuropathies, Painful
Intervention  ICMJE Drug: WST-057 (4% pirenzepine) Lose Dose 2mL
Topical Solution
Other Names:
  • WST-057 (4% pirenzepine) High Dose 4 mL
  • WST-057 Matching Placebo Low Dose 2mL
  • WST-057 Matching Placebo High Dose 4mL
Study Arms  ICMJE
  • Placebo Comparator: Placebo Low Dose
    WST-057 Matching placebo 2 mL volume
    Intervention: Drug: WST-057 (4% pirenzepine) Lose Dose 2mL
  • Placebo Comparator: Placebo High Dose
    WST-057 Matching placebo 4mL volume
    Intervention: Drug: WST-057 (4% pirenzepine) Lose Dose 2mL
  • Experimental: Active Low Dose
    WST-057 2mL volume
    Intervention: Drug: WST-057 (4% pirenzepine) Lose Dose 2mL
  • Experimental: Active High Dose
    WST-057 4mL volume
    Intervention: Drug: WST-057 (4% pirenzepine) Lose Dose 2mL
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 28, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2021
Estimated Primary Completion Date October 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of T2DM (as defined by the 2013 Diabetes Canada guidelines).
  2. Male and female patients in the age range of 18 to 75 years (inclusive).
  3. Presence of definite diabetic neuropathy (as defined by the Toronto Consensus Guidelines) of at least 12 months duration in the lower extremities.
  4. Provide written informed consent prior to entering the study or undergoing any study procedures.
  5. 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 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 (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.
  6. 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)
  7. Sural nerve response must be present and at least 1 µV in amplitude.
  8. Patients must have a screening IENF density range of no less than 1 IENF/mm and no more than 10 IENF/mm.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Fluency (oral and written) in the language in which the standardized tests will be administered.

Exclusion Criteria:

  1. Lower leg IENFD at screening of < 1 or >10 IENF/mm.
  2. Sural nerve amplitude of < 1 microvolts (µV) at the ankle.
  3. Proliferative retinopathy or maculopathy requiring acute treatment.
  4. Requiring dialysis.
  5. Impaired liver function, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal.
  6. Presence of clinically significant peripheral or autonomic neuropathy that is clearly of nondiabetic origin.
  7. Uncontrolled treated/untreated hypertension (systolic blood pressure [BP] greater than180 or diastolic BP greater than 100 at screening).
  8. Amputations of lower extremities or presence of foot ulcers.
  9. Clinically significant active macrovascular disease, including myocardial infarction or cerebrovascular event within the past 12 months.
  10. Uncontrolled or untreated hypothyroidism.
  11. Active infection (eg, HIV, hepatitis), or a history of severe infection during the 30 days prior to screening.
  12. Evidence of severely immunocompromised status.
  13. Major surgical procedure during the 90 days prior to screening.
  14. 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.
  15. Clinically significant gastric emptying abnormality (eg, severe gastroparesis).
  16. Urinary retention or an enlarged prostate.
  17. Uncontrolled glaucoma.
  18. Other clinically significant, active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary, 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.
  19. New treatment with (< 3 months) antioxidant supplements or drugs known to affect oxidative stress and peripheral diabetic neuropathy.
  20. Known or suspected history of alcohol or substance abuse.
  21. Mental incapacity, unwillingness, or language barrier precluding adequate understanding of or cooperation with the study.
  22. 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 additional menstrual cycle following the end-of treatment visit (see inclusion criterion 5).
  23. History of allergy or sensitivity to M1 antagonists or any of the components of the investigational product formulations.
  24. Known allergy or hypersensitivity to pirenzepine or another component of the investigational product.
  25. History of sensitive skin, as defined by a requirement to use soap and skin products formulated for "sensitive skin".
  26. Currently taking any medicines to treat overactive bladder (anticholinergic agents, such as Gelnique).
  27. Failure or inability to perform screening or baseline assessments.
  28. 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:
  29. Pain or neuropathy from another cause (including central pain, radiculopathy, painful arthritis, etc).
  30. Skin or soft-tissue lesions in the area affected by neuropathy that are painful or could alter sensation.
  31. Systemic infections (eg, HIV, hepatitis, tuberculosis, syphilis).
  32. Exposure to an experimental drug, experimental biologic, or experimental medical device within 3 months before screening.
  33. 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.
  34. History of a serious skin disease (as determined by the Investigator), such as skin cancer, psoriasis, or eczema.
  35. Receipt of a tattoo in the dosing area within 12 months of dosing.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Angela Hansen 858 848 4831 ahansen@winsantorbio.com
Contact: Stan Kim 858 336 8094 skim@winsantor.com
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04005287
Other Study ID Numbers  ICMJE WST-PZP-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: A paper will be published (made public)
Responsible Party WinSanTor, Inc
Study Sponsor  ICMJE WinSanTor, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Angela Hansen WinSanTor, Inc
PRS Account WinSanTor, Inc
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP