A Study To Investigate The Effect Of 28 Days Of Dosing With GW856553 On Patients With Rheumatoid Arthritis

NCT00393146 | Completed Phase 2

• 1 other identifier: RA3103718
• Study Type: interventional
• Target: 57
• Locations: 3 countries
• Sites: 15

Brief Summary

This study is designed to look at the safety, tolerability and effectiveness of 28 days of dosing of GW856553 in rheumatoid arthritis patients.

Conditions

Arthritis, Rheumatoid

Keywords

Rheumatoid arthritis; MRI

Outcome Measures

Primary Outcomes (1)

• Disease activity score based on 28 joint count (DAS28) at the end of the study.

  at the end of the study.

Secondary Outcomes (4)

• Adverse events, vitals signs, ECGs and clinical lab tests after 56 days.

  after 56 days.

• Plasma biomarkers after 56 days.

  after 56 days

• Population pharmacokinetics after 56 days

  after 56 days

• Gadolinium enhanced MRI scans after 56 days.

  after 56 days.

Interventions

GW856553 DRUG

Study drug

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject is male or female ≥ 18 years of age.
• To be eligible, female subjects must have a negative pregnancy test (i.e. serum beta hCG test) and be of:
• non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal. For the purposes of this study, post menopausal is defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. Postmenopausal status will be confirmed by serum FSH and oestradiol concentrations at screening. Surgical sterility will be defined as females who have had a hysterectomy and/or bilateral oophorectomy or tubal ligation. OR
• childbearing potential and agrees to commit to one of the protocol-approved methods of contraception as detailed in Section 7.1.
• Body weight ≥ 50 kg (110lbs) for males and ≥ 45 kg (99lbs) for females.
• Body mass index (BMI) within the range 18.5-35.0 kg/m2 inclusive.
• The subject has a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) (see Appendix 6).
• The subject must have DAS28 ≥ 4.2 (DAS28 calculated using ESR).
• The subject must have liver function (ALT, AST and total bilirubin) tests \< 1.5 x ULN at screening.
• The subject must have ALP \< 2 x ULN at screening.
• The subject must have normal serum folate levels at screening (folate supplements can be administered if required but this must be stable for 4 weeks prior to randomisation).
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
• Signed and dated written informed consent prior to admission to the study.

You may not qualify if:

• The subject has a three month prior history of regular alcohol consumption exceeding an average weekly intake of \> 21 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of \> 14 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a half-pint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol breath test at the screening visit.
• The subject has any history of liver disease.
• The subject has a positive Hepatitis B surface antigen or Hepatitis C antibody result within 3 months of the start of the study.
• The subject has a history of elevated liver function tests on more than one occasion (ALT, AST, and total bilirubin \> 2 x ULN or ALP \> 3 x ULN) in the past 7 months.
• The subject is currently receiving a biological anti-rheumatic therapy.
• The subject has failed more than one anti-TNFα biological therapy due to lack of efficacy.
• The subject received an anti-rheumatic biological therapy within 6 months (for i.v.
• administered therapies with long half-lives e.g. infliximab) or 3 months (for subcutaneously administered therapies or iv administered therapies with short halflives e.g. adalimumab or etanercept) prior to randomisation.
• The subject has received rituximab.
• The subject is using oral prednisolone at doses \> 10mg/day, methotrexate \> 25 mg/week or sulphasalazine \> 5g/day.
• The subject's DMARD dosing regimen has changed during the 4 weeks prior to randomisation.
• The subject's current DMARD regimen has changed significantly (i.e. likely to impact disease activity during the study period) within the 3 months prior to dosing e.g. addition of a DMARD, changes in dose of greater than 2.5mg for methotrexate.
• The subject has received leflunomide for less than 6 months prior to randomisation.
• The subject has failed more than 3 DMARDs.
• The subject's NSAIDs, COX-2 inhibitors or glucocorticoid dosing regimen changes at any time during four weeks prior to randomisation.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Bucharest, 11172, Romania

Location

GSK Investigational Site

Bucharest, 20983, Romania

Location

GSK Investigational Site

Moscow, 109240, Russia

Location

GSK Investigational Site

Moscow, 115093, Russia

Location

GSK Investigational Site

Moscow, 115522, Russia

Location

GSK Investigational Site

Moscow, 119049, Russia

Location

GSK Investigational Site

Moscow, 630117, Russia

Location

GSK Investigational Site

Saint Pertersburg, 196247, Russia

Location

GSK Investigational Site

Yaroslavl, 150003, Russia

Location

GSK Investigational Site

A Coruña, 15006, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28035, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

Related Publications (1)

• Yang S, Lukey P, Beerahee M, Hoke F. Population pharmacokinetics of losmapimod in healthy subjects and patients with rheumatoid arthritis and chronic obstructive pulmonary diseases. Clin Pharmacokinet. 2013 Mar;52(3):187-98. doi: 10.1007/s40262-012-0025-6.

  PMID: 23254770 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

6-(5-((cyclopropylamino)carbonyl)-3-fluoro-2-methylphenyl)-N-(2,2-dimethylprpyl)-3-pyridinecarboxamide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2006
• First Posted: October 26, 2006
• Study Start: October 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: May 13, 2015

Record last verified: 2015-05

Locations

RU (7); RO (2); ES (6)