A randomised, parallel group, placebo-controlled, double blind study to assess the safety and tolerability of SB-681323 at 7.5mg daily dose for 28 days and its effect on the levels of serum C-reactive protein (CRP) in subjects with rheumatoid arthritis (RA)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-002219-26-SE
• Date of registration: 14/07/2005
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline R&D Ltd
• Public title: A randomised, parallel group, placebo-controlled, double blind study to assess the safety and tolerability of SB-681323 at 7.5mg daily dose for 28 days and its effect on the levels of serum C-reactive protein (CRP) in subjects with rheumatoid arthritis (RA)
• Scientific title: A randomised, parallel group, placebo-controlled, double blind study to assess the safety and tolerability of SB-681323 at 7.5mg daily dose for 28 days and its effect on the levels of serum C-reactive protein (CRP) in subjects with rheumatoid arthritis (RA)
• Date of first enrolment: 08/09/2005
• Target sample size: 82
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-002219-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany, Hungary, Italy, Norway, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. The subject is male or female = 18 years of age.
2. Subject has a negative pregnancy test (i.e serum beta hCG test) and is of:
- non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is surgically sterile via hysterectomy or bilateral ligation or who is post-menopausal. For purposes of this study, postmenopausal is defined as one year without menses).
- child-bearing potential and agrees to commit to one of the protocol-approved methods of contraception, when used consistently and in accordance with both the product label and the instructions of a physician, as indicated below:
• oral contraceptive (combined or progestin only), and the same oral contraceptive regimen has been used for at least two months prior to study drug administration, and the same method continues throughout the study and through the 2 weeks following the end of the treatment phase of the study
• progesterone implanted rods (Norplant ) inserted for at least two month prior to the study drug administration (but not beyond the third successive year following insertion) , and is continued throughout the study, and for the 2 weeks following the end of the treatment phase of the study
• an IUD, inserted by a qualified clinician, with published data showing that the highest expected failure rate is less than 1% per year (not all IUDs meet this criterion) Acceptable IUDs: TCu-380A (Paragard), TCU-380 Slimline (Gyne T Slimline), TCu-220C, MULTILOAD-250 (MLCu-250) and 375, NOVA T and CUNOVAT (Novagard), Levonorgesterol (LNG-20) Intra-uterine System (Mirena/Levonova), and FlexiGard 330/CuFix PP330 (Gynefix). The device must be inserted at least 2 weeks prior to the Screen visit, and remain throughout the study and for the 2 weeks following end of the treatment phase of the study.
• injectable medroxyprogesterone acetate (e.g., Depo-Provera) and is on a stable dose for 2 months prior to Screen, throughout the study, and 2 weeks following the end of the treatment phase of the study
• complete abstinence from intercourse for two weeks prior to the study drug administration, throughout the treatment phase, and the follow-up phase
• double barrier method if comprised of a spermicide with either a condom or diaphragm.
3. Adult males and females with body weight >/= 50 kg for males and >/= 45 kg for females (Body Mass Index (BMI) within the range 18.5-35.0 kg/m2 inclusive).
4. The subject has a diagnosis of RA according to the revised 1987 ACR criteria.
5. The subject has active RA defined as, CRP >/= 15mg/l and a DAS28 score >/= 3.2
6. The subject must have normal Liver Function Tests (LFTs; i.e. ALT, AST, ALP, GGT and total bilirubin within normal limits) at Screening.
7. Those subjects who are on oral DMARDs (which may include methotrexate, sulphasalazine, hydroxychloroquine) must be on stable doses for at least eight weeks prior to Screening and continued on stable doses during the screening period. The subject may be using glucocorticoid at doses up to 10mg/day, methotrexate up to 25 mg/week or sulphasalazine up to 3g/day.
8. Those subjects who are on other oral anti-rheumatic therapies (which may include NSAIDs, COX-2 inhibitors and glucocorticoids) must be on stable dosing regimens for at least 4 weeks prior to Screening and during the screening period.
9. The subjects on stable doses of methotrexate must also be on stable folate supplements with normal red cell folate levels at screening.
10. The subject m
Exclusion criteria:
1. The subject is currently receiving a biological anti-rheumatic therapy or has failed to demonstrate a clinical response to a biological anti-rheumatic therapy, is using glucocorticoid at doses >10mg/day, methotrexate > 25 mg/week or sulphasalazine > 3g/day
2. The subject has a three month prior history of alcohol use >21 units per week for males and >14 units per week for females or the subject has a positive alcohol screen at the Screening visit
3. The subject has any history of liver disease
4. The subject has a positive Hepatitis B surface antigen or Hepatitis C antibody result within 3 months of the start of the study.
5. Subjects whose DMARDs change at any time during 8 weeks prior to screening or during the screening period..
6. Subjects whose NSAIDs, COX-2 inhibitors or glucocorticoids change at any time during 4 weeks prior to screening or during the Screening period.
7. The subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that, in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial.
8. The subject has an acute infection.
9. The subject has a history of active tuberculosis.
10. The subject has a history of repeated or chronic infections.
11. The subject has a history of malignancy, except for surgically cured basal cell carcinoma or females with cured cervical carcinoma (> 2 yrs prior).
12. The subject has a history of HIV or other immunosuppressive disease.
13. The subject has participated in a clinical trial within the 3 months prior to the study onset for non-biological therapy; or within 6 months of a biological therapy.
14. The subject has Hb <9 g/dL or platelet count < 100 000/mm3
15. The subject whose calculated creatinine clearance is less than 50ml/min
16. The subject has uncontrolled diabetes or psoriasis
17. The subject is pregnant or lactating



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis (RA)

Intervention(s)

Product Name: SB-681323 Tablets
Product Code: SB-681323
Pharmaceutical Form: Tablet
Current Sponsor code: SB-681323
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2,5 and 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: • To assess the effect of SB-681323 on Disease Activity Score based on 28 joint count (DAS28)
• To assess the safety and tolerability of SB-681323 in subjects with rheumatoid arthritis (RA)
• To assess the effect of SB-681323 on American College of Rheumatology (ACR) 20% response in a core set of rheumatologic assessments (ACR20)
• To assess the effect of SB-681323 on fatigue in subjects with RA
• To assess the effect of SB-681323 on relevant biomarkers of inflammation and joint damage
• To assess pharmacokinetics of SB-681323 in this subject population
• To explore the potential effects of concomitant medication on the pharmacokinetics of SB-681323
• To explore the potential correlation between plasma exposure to SB-681323 and disease surrogate (CRP) and clinical endpoints (ACR20 and DAS28)

Main Objective: To assess the effect of SB-681323 on the serum levels of C-reactive protein (CRP) in subjects with rheumatoid arthritis (RA)

Primary end point(s): Serum levels of CRP at the end of study (after 28 days of treatment) following repeat dosing with SB-681323 (7.5mg/day) compared with placebo

Secondary ID(s)

RA1100849