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

Painful Diabetic Peripheral Neuropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05123196
• Other study ID #: MT-8554-A-201
• Secondary ID: jRCT2051210097
• Status: Completed
• Phase: Phase 2
• Start date: November 16, 2021
• Est. completion date: November 8, 2022

Study information

• Verified date: November 2022
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: November 8, 2022
• Est. primary completion date: November 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Neuropathies
• Pain
• Painful Diabetic Peripheral Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• MT-8554
Oral Capsule
• Placebo
Oral Capsule

Locations

Country	Name	City	State
Japan	Yachiyo Hospital	Anjo-City	Aichi
Japan	Kumanomae Nishimura Naika Clinic	Arakawa-ku	Tokyo
Japan	Japanese Red Cross Asahikawa Hospital	Asahikawa-City	Hokkaido
Japan	Medical Corporation Keiaikai Nakamura Hospital	Beppu-City	Oita
Japan	JUNEIKAI Medical Corporation Akaicho Clinic	Chiba-shi	Chiba
Japan	Tokyo Center Clinic	Chuo-ku	Tokyo
Japan	Shonan Fujisawa Tokushukai Hospital	Fujisawa-shi	Kanagawa
Japan	Kunisaki Makoto Clinic	Fukuoka-Shi	Fukuoka
Japan	Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro Hospital	Fukuoka-shi	Fukuoka
Japan	TOJITAMA thyroid and diabetes Clinic	Fukuoka-shi	Fukuoka
Japan	Hakodate Central General Hospital	Hakodate-City	Hokkaido
Japan	Matsunami Health Promotion Clinic	Hashima-gun	Gifu
Japan	Steel Memorial Yawata Hospital	Kitakyushu-shi	Fukuoka
Japan	OMI MEDICAL CENTER, Social Medical Corporation Seikoukai	Kusatsu-City	Shiga
Japan	Kikuchi Clinic of Internal Medicine	Maebashi-city	Gunma
Japan	Shunkaikai Inoue Hospital	Nagasaki-shi	Nagasaki
Japan	Japan Organization of Occupational Health and Safety Chubu Rosai Hospital	Nagoya-City	Aichi
Japan	Sugawara Clinic	Nerima-ku	Tokyo
Japan	Jiyugaoka Yamada Internal Medicine Clinic	Obihiro-City	Hokkaido
Japan	Abe Diabetes Clinic	Oita-City	Oita
Japan	Medical Corporation Ikeikai Inobe Funai Clinic	Oita-City	Oita
Japan	Medical Corporation Kouhoukai Takagi Hospital	Okawa-shi	Fukuoka
Japan	Ome Municipal General Hospital	Ome-shi	Tokyo
Japan	Kitano Hospital, Tazuke Kofukai Medical Research Institute	Osaka
Japan	Hisatomi Clinic	Saga-City	Saga
Japan	Saiki Central Hospital	Saiki-City	Oita
Japan	Sanuki Municipal Hospital	Sanuki-shi	Kagawa
Japan	Medical Corporation Souaikai Aihara Medical Clinic	Shinagawa-ku	Tokyo
Japan	Medical Corporation Heishinkai ToCROM Clinic	Shinjuku-ku	Tokyo
Japan	Soka Sugiura Internal Medicine Clinic	Soka-City	Saitama
Japan	Medical Corporation Heishinkai OCROM Clinic	Suita-City	Osaka
Japan	Takamatsu Red Cross Hospital	Takamatsu-shi	Kagawa
Japan	Japan Organization of Occupational Health and Safety Sanin Rosai Hospital	Yonago	Tottori

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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