UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Clinical trial for efficacy and safety related to weekly dosage regimens of methotrexate
Title of the study (Brief title)	Clinical trial for Adverse event related to Weekly dosage regimens of Methotrexate (ADDMe trial)
Region	Japan

Condition
Condition	Rheumatoid arthritis
Classification by specialty	Clinical immunology Orthopedics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To compare the efficacy and safety when administered by dividing into 3 times and when administered at once doses per week of MTX (at a dose of over 8mg/week to 16mg/week) for RA patient who had not achieved remission despite 8mg/week or less dose of MTX for at least 4 weeks. As reference data, to compare MTX-PGs concentration in red blood cells of patients in both groups.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	The incidence of liver disfunction at Week 20.
Key secondary outcomes	The incidence of adverse events. The change in DAS28 at Week 20 from Week 0. The change in SDAI at Week 20 from Week 0. Concentrations of MTX polyglutamates in red blood cells at Week 0 and Week 20. Laboratery datas during obsevational term.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is considered as a block.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	administration of weekly MTX dose at once.
Interventions/Control_2	administration by dividing three times of weekly MTX dose.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1)Patients, fulfilled the ACR 1987 reviced criteria for the classification of rheumatoid arthritis and patients, fulfilled the ACR/EULAR 2010 criteria for the classification of rheumatoid arthritis. 2)RA patient who had not achieved remission despite 8mg/week or less dose of MTX for at least 4 weeks. 3)Patient who is within 14 days before change of MTX dose. 4)Patient who elapsed at least 8 weeks after if using biologics, JAK inhibitors or immunosuppressants (leflunomide, tacrolimus or mizolibine). 5) Outpatients (there are no schedules of hospitalization during a clinical trial period). 6) Patients who can provide written informed concent by themselves.
Key exclusion criteria	(Complication) Patients who had any of the following diagnoses or medical history 1)Autoimmune disease, except for RA and Sjogren's syndrome, and malignancy. 2)Drug allergy 3)Severe heart, lung, liver, kidney and heamatological disorders (Treatment) 4)Patient who recived intramuscular, intoravenous or epidural injection of corticosteroids within 4 weeks prior to the entry or during study 5)Patient who recived intraarticular corticosteroid at dose of over 20mg/month of prednisolone, and at any dose within 4weeks prior to study entry or first end point 6)Pateint whose body weight is less than or equal to 40kg 7)Patient who recived systemic corticosteroid with a dose of>10mg of predonisolone within 4 weeks prior to the study or during the study and patients whose corticosteroid dose were changed within 4 weeks prior to first end point 8)Patient who received NSAIDs with an overdosage within 4 weeks prior to the study entry or during the study. 9) Patient who is currently under treatment or treatmented with biologics, JAK inhibitor or immunosappressants within 8 weeks prior to the study entry. (Surgery) 10)Patient who had surgery judged to have an influence on this study by doctor 11)Patient who had the following treatment or procedure:plasma exchange, leukocyte depleted therapy or arthrocentesis against affected joint. except for the arthrocenesis following intraarticular injection of corticosteroid, within 4 weeks prior to the study entry or during the study (Others) 12)Patient who is in pregnancy, lactating, or with a possibility of the pregnancy and woman who hopes for pregnancy during study or within 1 month after the end of this study, and man who wishes his partner be pregnant during the study or within 3 months after the end of this study 13)Patient who can not go to a hospital for check-up on an appointed day 14)When principal investigator or sub investigators of this study judge the patients disqualified as a subject of this study
Target sample size	120

Research contact person
Name of lead principal investigator	Shohei Nagaoka
Organization	Yokohama Minami Kyousai Hospital
Division name	Deputy director
Address	1-21-1, Rikuurahigashi, Kanazawa-ku, Yokohama City, Kanagawa
TEL	045-782-2101
Email	nagaokacrt@msn.com

Public contact
Name of contact person	Masahiro Okamoto
Organization	AYUMI Pharmaceutical Corporation
Division name	Department of Medical Affers, Division of Research and Development
Address	105 Jibu-cho, Fushimi-ku, Kyoto City, Kyoto
TEL	075-632-9700
Homepage URL
Email	masahiro.okamoto@ayumi-pharma.com

Sponsor
Institute	Yokohama Minami Kyousai Hospital
Institute
Department

Funding Source
Organization	None
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor	AYUMI Pharmaceutical corporation
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

横浜南共済病院（神奈川）Yokohama Minami Kyousai Hospital（Kanagawa) 佐川昭リウマチクリニック（北海道）Sagawa Akira Rheumatology Clinic（Hokkaido) 片山整形外科リウマチ科クリニック（北海道）Katayama Orthopedic Rheumatology Clinic（Hokkaido） 横浜市立大学附属　市民総合医療センター（神奈川）Yokohama City University Medical Center（Kanagawa) 松波総合病院　リウマチセンター（岐阜）Matsunami General Hospital Rheumatology Center （Gifu) 昭和大学江東豊洲病院（東京）Showa University Koto Toyosu Hospital（Tokyo) KKR札幌医療センター斗南病院（北海道）KKR Sapporo Medical Center Tonan Hospital（Hokkaido) 市立札幌病院（北海道）Sapporo City General Hospital（Hokkaido) 国立病院機構北海道医療センター（北海道）Hokkaido Medical Center（Hokkaido) 手稲渓仁会病院（北海道）Teine Keijinkai Hospital（Hokkaido）

Other administrative information
Date of disclosure of the study information	2016 Year 02 Month 29 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 01 Month 29 Day
Anticipated trial start date	2016 Year 03 Month 01 Day
Last follow-up date	2017 Year 08 Month 31 Day
Date of closure to data entry	2017 Year 09 Month 30 Day
Date trial data considered complete	2017 Year 12 Month 31 Day
Date analysis concluded	2018 Year 01 Month 16 Day

Related information
URL releasing protocol
Publication of results	Published
URL releasing results	https://ard.bmj.com/content/77/Suppl_2/992.1
Results
Other related information

Management information
Registered date	2016 Year 02 Month 23 Day
Last modified on	2018 Year 08 Month 02 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024008