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

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

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.

Inclusion Criteria:

1. Patients with written consent

2. Patients aged >=20 years at the time of consent

3. Outpatients

4. 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

5. 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.

6. 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%.

7. 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:

1. 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.

2. Patients who have had amputation of upper and lower limbs other than toes due to gangrene caused by impaired blood circulation.

3. Patients who do not meet the criteria of prohibited concomitant drugs or restricted concomitant drugs.

4. Patients with hypersensitivity to acetaminophen or a history of hypersensitivity to acetaminophen.

5. Patients with New York Heart Association functional class III or IV symptoms of heart failure.

6. History of myocardial infarction, congestive heart failure, unstable angina, or cerebrovascular disorder (excluding lacunar infarction) within 6 months prior to informed consent.

7. Patients with major psychiatric disorder such as depression or anxiety disorder.

8. Patients with drug abuse or a history of drug abuse.

9. 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.

10. Patients with HbA1c > 10.5%.

11. Patients with poorly controlled hypertension (>= 180 mmHg systolic and/or >= 110 mmHg diastolic).

12. Patients with eGFR < 30 mL/min/1.73 m^2.

13. Patients with AST or ALT > 2.5*ULN.

14. Patients who answered "Yes " to any item of Columbia Suicide Severity Rating Scale within the past 12 months.

15. 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.

16. 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.

17. Female patients who are pregnant, breastfeeding or possibly pregnant.

18. Patients who participated in another clinical study and received investigational product within 12 weeks before informed consent.

19. Prior exposure to MT-8554.

20. Other patients who, in the opinion of the investigator (or sub-investigator), are ineligible for this study.