Clinical trial NCT05123196: Exploratory Study of MT-8554 in Subjects With Painful Diabetic Peripheral Neuropathy
Official title: A Randomized, Double-Blind, Placebo-Controlled, Exploratory Study of MT-8554 in Subjects With Painful Diabetic Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Painful Diabetic Peripheral Neuropathy
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2021-11-17
Enrollment: 156
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in the weekly mean 24-hour average NRS score at Week 12 in treatment period
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change from baseline in weekly mean 24-hour average NRS score at each assessment point
timeFrame: Up to Week 12
measure: Average weekly 24-hour NRS score during the 12 week treatment period 30% and 50% responder rates
timeFrame: Baseline and Week 12
measure: Change from baseline in weekly mean daily NRS score at each assessment point
timeFrame: Up to Week 12
measure: Change from baseline in weekly mean nocturnal average NRS score at each assessment point
timeFrame: Up to Week 12
measure: Change from baseline in weekly mean 24 hour worst NRS score at each assessment point
timeFrame: Up to Week 12
measure: Change from baseline in NPSI at each assessment point
timeFrame: Up to Week 12
measure: Change from baseline in BPI pain severity at each assessment point
timeFrame: Up to Week 12
measure: Change from baseline in BPI functional impairment at each assessment point
timeFrame: Up to Week 12
measure: Change from baseline in MOS-SS at each assessment point
timeFrame: Up to Week 12
measure: Proportion of PGIC responders at each assessment point
timeFrame: Up to Week 12
measure: Proportion of CGIC responder at each assessment point
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Anjo-City
country: Japan
facility: Yachiyo Hospital
state: Aichi
city: Nagoya-City
country: Japan
facility: Japan Organization of Occupational Health and Safety Chubu Rosai Hospital
state: Aichi
city: Chiba-shi
country: Japan
facility: JUNEIKAI Medical Corporation Akaicho Clinic
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Social Medical Corporation the Chiyukai foundation Fukuoka Wajiro Hospital
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: TOJITAMA thyroid and diabetes Clinic
state: Fukuoka
city: Fukuoka-Shi
country: Japan
facility: Kunisaki Makoto Clinic
state: Fukuoka
city: Kitakyushu-shi
country: Japan
facility: Steel Memorial Yawata Hospital
state: Fukuoka
city: Okawa-shi
country: Japan
facility: Medical Corporation Kouhoukai Takagi Hospital
state: Fukuoka
city: Hashima-gun
country: Japan
facility: Matsunami Health Promotion Clinic
state: Gifu
city: Maebashi-city
country: Japan
facility: Kikuchi Clinic of Internal Medicine
state: Gunma
city: Asahikawa-City
country: Japan
facility: Japanese Red Cross Asahikawa Hospital
state: Hokkaido
city: Hakodate-City
country: Japan
facility: Hakodate Central General Hospital
state: Hokkaido
city: Obihiro-City
country: Japan
facility: Jiyugaoka Yamada Internal Medicine Clinic
state: Hokkaido
city: Sanuki-shi
country: Japan
facility: Sanuki Municipal Hospital
state: Kagawa
city: Takamatsu-shi
country: Japan
facility: Takamatsu Red Cross Hospital
state: Kagawa
city: Fujisawa-shi
country: Japan
facility: Shonan Fujisawa Tokushukai Hospital
state: Kanagawa
city: Nagasaki-shi
country: Japan
facility: Shunkaikai Inoue Hospital
state: Nagasaki
city: Beppu-City
country: Japan
facility: Medical Corporation Keiaikai Nakamura Hospital
state: Oita
city: Oita-City
country: Japan
facility: Medical Corporation Ikeikai Inobe Funai Clinic
state: Oita
city: Oita-City
country: Japan
facility: Abe Diabetes Clinic
state: Oita
city: Saiki-City
country: Japan
facility: Saiki Central Hospital
state: Oita
city: Suita-City
country: Japan
facility: Medical Corporation Heishinkai OCROM Clinic
state: Osaka
city: Saga-City
country: Japan
facility: Hisatomi Clinic
state: Saga
city: Soka-City
country: Japan
facility: Soka Sugiura Internal Medicine Clinic
state: Saitama
city: Kusatsu-City
country: Japan
facility: OMI MEDICAL CENTER, Social Medical Corporation Seikoukai
state: Shiga
city: Arakawa-ku
country: Japan
facility: Kumanomae Nishimura Naika Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Tokyo Center Clinic
state: Tokyo
city: Nerima-ku
country: Japan
facility: Sugawara Clinic
state: Tokyo
city: Ome-shi
country: Japan
facility: Ome Municipal General Hospital
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Medical Corporation Souaikai Aihara Medical Clinic
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Medical Corporation Heishinkai ToCROM Clinic
state: Tokyo
city: Yonago
country: Japan
facility: Japan Organization of Occupational Health and Safety Sanin Rosai Hospital
state: Tottori
city: Osaka
country: Japan
facility: Kitano Hospital, Tazuke Kofukai Medical Research Institute
Study officials:
affiliation: Mitsubishi Tanabe Pharma Corporation
name: General Manager
role: STUDY_DIRECTOR
References: