A phase 2, multi-centre, randomised, double blind, placebo controlled study evaluating the efficacy, safety and pharmacokinetics of two doses of a candidate Disease Modifying Anti-Rheumatic Drug (DMARD), (SMP-114 120 mg and 240 mg once daily), administered in combination with ongoing methotrexate treatment in patients with active rheumatoid arthritis. - ASPECTS- Assessment of Safety, Pharmacokinetics and Efficacy in a Combination Treatment with SMP-114

• Conditions: MedDRA version: 8.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis; Rheumatoid Arthritis

• Registration Number: EUCTR2005-003436-21-DE
• Lead Sponsor: Dainippon Sumitomo Pharma Europe Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10-24
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1.Is at least 18 years of age
2.Has given his/her written informed consent to participate in the study
3.Has had a diagnosis of RA (based on the ACR criteria) for at least 6 months
4.Has RA disease classified as ACR functional class I, II or III
5.Has active RA disease as defined by:
·= 6 swollen joints (using 28-joint counts)
·= 6 tender joints (using 28-joint counts)
·and at least one of the following: ESR = 28 mm/hr, CRP = 10 mg/L
6.Has been receiving methotrexate at weekly doses of 10 to 25 mg for = 12 weeks prior to study drug administration. Methotrexate use must have been in accordance with its product labelling (SmPC)
7.The dose of methotrexate has been stable for at least 8 weeks prior to randomisation and is anticipated to remain constant during the study period Individuals previously treated with methotrexate can be enrolled provided they have not had clinically significant toxic effects or lack of response, at the discretion of the Investigator
8.Has been on a stable dose of folate (or leucovorin) for at least 4 weeks prior to randomisation and the dose of folate (or leucovorin) is anticipated to remain constant during the study period. If not currently prescribed, is willing to start receiving folate (or leucovorin) at screening
9.If on a stable dose of NSAID and/or COX-2 inhibitor, the doses of these concomitant medications must have been stable for at least 2 weeks prior to randomisation. The dose(s) must be anticipated to remain constant during the study
10.If taking oral corticosteroid at a permissible dose (eg = 10 mg prednisolone) then the dose of the oral corticosteroid must have been stable for at least 4 weeks prior to randomisation and must be anticipated to remain constant during the study

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients are not eligible for this study if they fulfil any of the following criteria:

1.Is a pregnant or lactating woman
2.Is a woman of childbearing potential not prepared to use a reliable form of contraception during the study. An effective form of birth control includes contraception such as a barrier method (condom with spermicidal) in conjunction with hormone-based contraceptives or certain intra-uterine devices, or alternatively abstinence or surgical methods.
3.Has previously discontinued DMARD therapy due to hepatic intolerance.
4.Has received any DMARD in addition to methotrexate during the 4 weeks prior to randomisation. All DMARD’s, with the exception of methotrexate must have been discontinued at least 4 weeks before randomisation, unless requiring a longer washout period
5.Is receiving more than 2 DMARDs in addition to methotrexate at the time of screening
6.Is receiving or has received Gold, leflunomide or biological agents including TNF/IL-1 inhibitors within the 8 weeks prior to randomisation. Leflunomide washout can be completed with colestyramine according to the manufacturer’s instructions
7.Has previously failed =2 DMARDS. Failure is defined as removal of the administration of a DMARD due to inadequate efficacy response rather than discontinuation of DMARD therapy due to intolerance. A patient who has been removed from biological DMARD therapy due to non-clinical reasons can enter the study
8.Will require any treatments contraindicated for methotrexate
9.Is currently taking flurbiprofen
10.Has used intra-articular, intra-muscular or intravenous corticosteroids within 8 weeks prior to randomisation
11.Requires ongoing treatment with warfarin, cimetidine, phenytoin, trimethoprim, quinolones or dextropropoxyphenes (including co-proxamol) during the study
12.Persistent or severe infections within 3 months before randomisation
13.Has any known or suspected hypersensitivity to leflunomide or any other isoxazole compounds or any ingredients contained within the study drug (mannitol, corn starch, croscarmellose sodium, hypromellose, magnesium stearate, titanium dioxide, macrogol, carnuba wax, gelatine, sodium metabisulphite)
14.Has pre-existing hepatic disease, or co morbid illness predisposing to hepatic complications and/or the following laboratory parameters at screening:
·AST = 2 X ULN on two consecutive occasions and/or
·ALT = 2 X ULN on two consecutive occasions
15.Has any pre-existing renal disease, or co morbid illness predisposing to renal complications, or the following laboratory parameter at screening:
·Serum creatinine = 1.5 mg/dL
16.Has current blood dyscrasias such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anaemia including Haemoglobin <10 g/dL at screening
17.Has any other significant systemic, cardiac, neurological, psychiatric or other illness that in the Investigator’s opinion would preclude the patient from participating in the study
18.Has a known or had a known malignancy of any type in the previous 5 years with the exception of basal or squamous cell carcinoma of the skin if no recurrence during the 1 year prior to screening
19.Has a current history of known or in the opinion of the Principal Investigator, suspected drug and/or alcohol abuse
20.Has participated in another clinical trial with an investigational agent (including named patient or compassionate use protocols) 8 weeks prior to randomisation (or longer if 8 weeks

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified