Exploratory Study of MT-8554 in Subjects With Painful Diabetic Peripheral Neuropathy

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy, safety, tolerability and pharmacokinetics of MT-8554, compared to placebo, in subjects with painful diabetic peripheral neuropathy.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Exploratory Study of MT-8554 in Subjects With Painful Diabetic Peripheral Neuropathy

Conditions
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Painful Diabetic Peripheral Neuropathy

Intervention / Treatment
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* Drug: MT-8554
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with written consent Patients aged >=20 years at the time of consent Outpatients Patients with pain associated with peripheral symmetric polyneuropathy due to diabetes mellitus and pain lasting >=3 months on the first day of the run-in period. The patient should meet >=2 of the following criteria or nerve conduction studies showing abnormalities in at least one test item (Conduction velocity, amplitude, and latency) for at least two nerves by the first day of run-in period. 1. Subjective symptoms* thought to be due to diabetic polyneuropathy 2. Decreased or eliminated bilateral Achilles tendon reflexes 3. Bilateral decreased vibratory sense of the medial malleolus (=< 10 seconds with a C 128 tuning fork) *Subjective symptoms thought to be due to diabetic neuropathy meet the following 3 criteria. Bilateral Toe and plantar symptoms (Numbness, pain or dysesthesia) Does not cause upper extremity symptoms alone Patients whose NRS during the run-in period is assessed for >=4 days of the 7 days immediately before the first day of the treatment period and whose baseline 24-hour mean NRS score is >=4 and =<8. Patients whose rate of change in the 24-hour mean NRS score during the 7 days immediately before the first day of the treatment period is <30%. Patients whose treatment for diabetes mellitus is consistent >=8 weeks before the run-in period, who can consistently maintain the treatment throughout the study period, and in whom the investigator (or sub-investigator) can determine that glycemic control is constant. Exclusion Criteria: Patients with pain, disease, or skin condition that, in the opinion of the investigator (or sub-investigator), would influence the evaluation of painful diabetic peripheral neuropathy. For example, if other pain is in the same location as painful diabetic peripheral neuropathy, or if the pain intensity of the other pain is greater than that of painful diabetic peripheral neuropathy, which in the opinion of the investigator (or sub-investigator) would impact the assessment of painful diabetic peripheral neuropathy. Patients who have had amputation of upper and lower limbs other than toes due to gangrene caused by impaired blood circulation. Patients who do not meet the criteria of prohibited concomitant drugs or restricted concomitant drugs. Patients with hypersensitivity to acetaminophen or a history of hypersensitivity to acetaminophen. Patients with New York Heart Association functional class III or IV symptoms of heart failure. History of myocardial infarction, congestive heart failure, unstable angina, or cerebrovascular disorder (excluding lacunar infarction) within 6 months prior to informed consent. Patients with major psychiatric disorder such as depression or anxiety disorder. Patients with drug abuse or a history of drug abuse. Patients with current or previous infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). However, patients with previous infection with hepatitis B virus who are HBsAg-negative are eligible. Patients with HbA1c > 10.5%. Patients with poorly controlled hypertension (>= 180 mmHg systolic and/or >= 110 mmHg diastolic). Patients with eGFR < 30 mL/min/1.73 m^2. Patients with AST or ALT > 2.5*ULN. Patients who answered Yes  to any item of Columbia Suicide Severity Rating Scale within the past 12 months. Patients who have a concomitant malignancy or a history of malignancy. However, patients who have a history of malignancy but have not experienced recurrence for at least 5 years before informed consent (patients who have not experienced recurrence for at least 5 years after the last administration if the patients were receiving anticancer drugs) will be excluded. Male or female patients of childbearing potential who do not agree to use contraception from the date of informed consent until 3 months after the completion (discontinuation) of investigational product. Female patients who are pregnant, breastfeeding or possibly pregnant. Patients who participated in another clinical study and received investigational product within 12 weeks before informed consent. Prior exposure to MT-8554. Other patients who, in the opinion of the investigator (or sub-investigator), are ineligible for this study.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-8554<br>MT-8554 will be started from a low dose, and gradually increase the dose in order. | Drug: MT-8554<br>* Oral Capsule<br>* Other names: Elismetrep;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the weekly mean 24-hour average NRS score at Week 12 in treatment period | Numeric Rating Scale (NRS) is the 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain). Higher NRS scores indicated worse outcome. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in weekly mean 24-hour average NRS score at each assessment point | Numeric Rating Scale (NRS) is the 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain). Higher NRS scores indicated worse outcome. | Up to Week 12 | 
| Average weekly 24-hour NRS score during the 12 week treatment period 30% and 50% responder rates | Numeric Rating Scale (NRS) is the 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain). Higher NRS scores indicated worse outcome. | Baseline and Week 12 | 
| Change from baseline in weekly mean daily NRS score at each assessment point | Numeric Rating Scale (NRS) is the 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain). Higher NRS scores indicated worse outcome. | Up to Week 12 | 
| Change from baseline in weekly mean nocturnal average NRS score at each assessment point | Numeric Rating Scale (NRS) is the 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain). Higher NRS scores indicated worse outcome. | Up to Week 12 | 
| Change from baseline in weekly mean 24 hour worst NRS score at each assessment point | Numeric Rating Scale (NRS) is the 11-point numerical rating scale of 0 (no pain) to 10 (worst possible pain). Higher NRS scores indicated worse outcome. | Up to Week 12 | 
| Change from baseline in NPSI at each assessment point | Neuropathic Pain Symptom Inventory (NPSI) is the questionnaire to evaluate the different symptoms of neuropathic pain and each symptoms are evaluated from 0 (no pain) to 10 (worst possible pain). Higher NPSI scores indicated worse outcome. | Up to Week 12 | 
| Change from baseline in BPI pain severity at each assessment point | Brief Pain Inventory (BPI) is the questionnaire to assess the severity of pain from 0 (no pain) to 10 (pain as bad as patient can imagine). Higher BPI scores indicated worse outcome. | Up to Week 12 | 
| Change from baseline in BPI functional impairment at each assessment point | Brief Pain Inventory (BPI) is the questionnaire to assess the impact of pain on daily functions from 0 (does not interfere) to 10 (completely interferes). Higher BPI scores indicated worse outcome. | Up to Week 12 | 
| Change from baseline in MOS-SS at each assessment point | Medical Outcomes Study-Sleep Scale (MOS-SS) is the questionnaire to evaluate the sleep disorder  snoring sleep arousal with shortness of breath or headache sleep sufficiency somnolence and amount of sleep/optimal sleep ranges from 0 (all of the time) to 6 (none of the time). Lower MOS-SS scores indicated worse outcome. | Up to Week 12 | 
| Proportion of PGIC responders at each assessment point | Patient Global Impression of Change (PGIC) is a questionnaire to evaluate the overall impression of pain improvement by patient from 1 (very much improved) to 7 (very much worse). Higher PGIC scores indicated worse outcome. | Up to Week 12 | 
| Proportion of CGIC responder at each assessment point | Clinician Global Impression of Change (CGIC) a questionnaire to evaluate the overall impression of pain improvement by clinician from 1 (very much improved) to 7 (very much worse). Higher CGIC scores indicated worse outcome. | Up to Week 12 |