Efficacy and Safety Study of MP-435 in Combination With Methotrexate (MTX) in Patients With Rheumatoid Arthritis

A Multicenter Randomized, Double-blind, Placebo-controlled Study of MP-435 in Combination With MTX in Patients With Rheumatoid Arthritis - Exploratory Study

The purpose of this study is to determine the Efficacy, Safety, and Pharmacokinetics of MP-435 administered for 12 weeks in subjects with rheumatoid arthritis (RA) on stable doses of Methotrexate.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: MP-435(dose1) + Methotrexate; Drug: Placebo + Methotrexate

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with a diagnosis of RA according to the diagnostic criteria of the American College of Rheumatology (ACR) (revised in 1987) for at least 6 months.
• Subjects who inadequately response for stable dose of MTX.

Exclusion Criteria:

• Patients with Class IV functional activity by the Steinbrocker's scale.
• Patients who have received a biological agent in the past.
• Patients who have other rheumatic diseases, or who have other diseases with joint symptoms.
• Patients with severe or uncontrolled endocrine, psychiatric, cardiac, hematological, pulmonary, hepatic, kidney, gastrointestinal, or thyroid disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Drug: Placebo + Methotrexate; Placebo + stable weekly dose of Methotrexate
Experimental: 1; dose1	Drug: MP-435(dose1) + Methotrexate; MP-435 dose1 + stable weekly dose of Methotrexate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response	ACR 20 response is a decrease of at least 20 per cent in both tender and swollen joint count [TJC and SJC] and in 3 to 5 assessments (participant's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ-DI]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]).	Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving ACR 50 Response	ACR 50 response is a decrease of at least 50 per cent in both tender and swollen joint count and in 3 to 5 assessments (participant's assessment of pain VAS with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; HAQ-DI: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; CRP).	Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time)
Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response	ACR 70 response is a decrease of at least 70 per cent in both tender and swollen joint count and in 3 to 5 assessments (participant's assessment of pain VAS with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; HAQ-DI: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; CRP).	Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time)
Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components	DAS28 (CRP) is calculated using TJC, SJC C-Reactive Protein ( CRP in mg/dL ), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.36 x log (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. DAS28 (ESR) is calculated using TJC, SJC erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x log (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative change score indicates improvement. Higher score indicated more disease activity. DAS28 =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity.	LOCF (Week 12 or discontinuation time)
Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components	ACR components are tender joints count (TJC), swollen joints count (SJC), participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR).	LOCF (Week 12 or discontinuation time)

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 11, 2010
• First Posted (Estimate): June 14, 2010

Study Record Updates

• Last Update Posted (Estimate): October 13, 2014
• Last Update Submitted That Met QC Criteria: October 7, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: MP-435-J04