UMIN-CTR Clinical Trial

Public title

Study for variations of safety and efficacy profile caused by division of weekly dose of methotrexate
(preliminary study)

Acronym

SAME study

Scientific Title

Study for variations of safety and efficacy profile caused by division of weekly dose of methotrexate
(preliminary study)

Scientific Title:Acronym

SAME study

Region

Japan

Condition

Rheumatoid arthritis

Classification by specialty

Clinical immunology

Orthopedics

Classification by malignancy

Others

Genomic information

NO

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 for rheumatoid arthritis patients.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Adverse event rates by questionnaire in observation period

Key secondary outcomes

SDAI of 12 weeks and 19 weeks from the start of observation period
DAS28 of 12 weeks and 19weeks from the start of observation period
Concentration of MTX polyglutamates in red blood cells
Laboratory test values in observation period

Study type

Interventional

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 not considered as adjustment factor.

Blocking

NO

Concealment

Numbered container method

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

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) Patients that are determined to need additional doses above 8mg / week despite of treatment with methotrexate
3) Outpatients (there are no schedules of hospitalization during a clinical trial period).
4) 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 patients who recieved intraarticular corticosteroid at any dose within 4weeks prior to study entry or the day for observation of first end point
6)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 the day for observation of first end point
7)Patient who received NSAIDs with an overdosage within 4 weeks prior to the study entry or during the study
(Surgery)
8)Patient who had surgery judged to have an influence on this study by doctor
9)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)
10)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
11)Patient who can not go to a hospital for check-up on an appointed day
12)When principal investigator or sub investigators of this study judge the patients disqualified as a subject of this study

Target sample size

40

Name of lead principal investigator

1st name
Middle name
Last name	Shohei Nagaoka

Organization

Yokohama Minami Kyousai Hospital

Division name

Deputy director

Zip code

Address

1-21-1, Rikuurahigashi, Kanazawa-ku, Yokohama City, Kanagawa

TEL

045-782-2101

Email

nagaokascrt@msn.com

Name of contact person

1st name
Middle name
Last name	Masahiro Okamoto

Organization

Santen Pharmaceutical CO.,Ltd.

Division name

Rheumatology Research & Development Center

Zip code

Address

8916-16, Takayama-cho, Ikoma City, Nara

TEL

0743-79-4736

Homepage URL

Email

masahiro.okamoto@santen.co.jp

Institute

Yokohama Minami Kyousai Hospital
Santen Pharmaceutical CO.,Ltd.

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Santen Pharmaceutical CO.,Ltd.

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

横浜南共済病院（神奈川県）　　　Yokohama Minami Kyousai Hospital（Kanagawa）
　　　
参天製薬株式会社　奈良開発研究センター（奈良県）Santen Pharmaceutical CO.,Ltd. Nara R&D center (Nara)

Date of disclosure of the study information

2013

Year

12

Month

04

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

http://ard.bmj.com/content/74/Suppl_2/260.2.abstract?sid=36807678-3c45-42f7-8619-1b9a5d92f398

Number of participants that the trial has enrolled

Results

There were no significant differences in the average of age , disease duration (5.8yr), and baseline DAS28(CPR)(2.84) between two groups. There were also no differences in the improvement of DAS28(CPR)(-0.95 vs -0.75) between two groups and weekly MTX dose(11.5mg vs 11.4mg) . Three adverse events were observed only in 3-dose regimen group . The remarkable difference was observed in MTX-PGs(18.8%), 3-dose regimen group showed significantly higher concentration of MTX-PG1+2 than single-dose group. On the other hand, 3-doses regimen group showed slight lower MTX-PG4+5 than single-dose regimen group, and there was no difference in MTX-PG3. The efficacy did not show significant difference between two groups. Liver function may be affected by concentration of MTX-PG1+2, which elevated in divided dosage regimen group. Further investigation is required in a larger population.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

11

Month

15

Day

Date of IRB

Anticipated trial start date

2013

Year

12

Month

03

Day

Last follow-up date

2014

Year

12

Month

11

Day

Date of closure to data entry

2015

Year

02

Month

28

Day

Date trial data considered complete

2015

Year

02

Month

28

Day

Date analysis concluded

2015

Year

03

Month

31

Day

Other related information

Poster presentation in EULAR2015

Registered date

2013

Year

12

Month

03

Day

Last modified on

2015

Year

07

Month

06

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014532