Study Of SB-683699 Compared To Placebo In Subjects With Relapsing-Remitting Multiple Sclerosis (MS)

NCT ID: NCT00395317

Last Updated: 2012-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 343 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2010-08-31

Brief Summary

SB-683699 is an oral medication that is thought to reduce the number of active white blood cells entering the brain; these white blood cells are part of the disease process for MS. This study will look at whether different doses of SB-683699 are effective and safe in patients with relapsing remitting MS.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm 1

placebo (4 tablets)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

placebo tablet

Arm 2

SB-683699 150 mg bid (1 x 150mg + 3 placebo tablets)

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

placebo tablet

Firategrast 150 mg

Intervention Type: DRUG

150 mg tablet

Arm 3

SB-683699 600 mg bid (2 x 300mg + 2 placebo tablets)

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

placebo tablet

Firategrast 300 mg

Intervention Type: DRUG

300 mg tablet

Arm 4

SB-683699 900 mg bid (3 x 300 mg + 1 placebo tablet)

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

placebo tablet

Firategrast 300 mg

Intervention Type: DRUG

300 mg tablet

Arm 5

SB-683699 1200 mg bid, male subjects only (4 x 300 mg tablets)

Group Type: EXPERIMENTAL

Firategrast 300 mg

Intervention Type: DRUG

300 mg tablet

Interventions

Placebo

placebo tablet

Intervention Type: OTHER

Firategrast 150 mg

150 mg tablet

Intervention Type: DRUG

Firategrast 300 mg

300 mg tablet

Intervention Type: DRUG

Other Intervention Names

SB-683699; SB-683699

Eligibility Criteria

Inclusion Criteria

• Written informed consent
• Males or females, aged 18 to 65, inclusive
• A diagnosis of relapsing-remitting MS [Polman, 2005; McDonald, 2001] with dissemination in time and space
• EDSS of between 0 and 6.0 inclusive at the Screening visit
• Occurrence of at least two relapses in previous 24 months with at least one relapse or documented evidence of gadolinium-enhancement on MRI (prior to screening) in the previous 12 months. Subject must not have had a relapse within 4 weeks prior to Screening. In addition, subjects experiencing a relapse between Screen and Visit 3 will not be eligible to be randomized.
• A minimum of five T2 lesions on brain MRI at Visit 2 as determined by the central MRI analysis reader
• A female subject is eligible to enter the study if she is:

• Of non-childbearing potential, i.e. women who:
• have documented evidence of tubal ligation, bilateral oophorectomy or hysterectomy; or
• are post-menopausal, defined as at least one year without menses in the absence of hormone replacement therapy. In questionable cases, menopausal status will be confirmed by oestradiol and FSH levels consistent with menopause according to local laboratory ranges. Oestrogen-containing hormone replacement therapies are not allowed during the study.
• Of childbearing potential, has a negative urine pregnancy test at Screening, and agrees to the consistent and correct use of one of the methods of contraception listed below. Subjects will use this contraceptive method for at least one month prior to Screening and should continue to use the same contraceptive method throughout the study until at least 3 days after the last dose of investigational product.
• Progesterone-only oral contraceptives or implants (inserted at least one month prior to Screening, but not beyond the third successive year following insertion). Oestrogen-containing contraceptives are not allowed during the study.
• Intra-uterine device (IUD) inserted by a qualified clinician. The IUD must have published data showing that the highest expected failure rate is less than 1% per year.
• Spermicide in conjunction with either a diaphragm, cervical cap or condom. Male partner sterilization (vasectomy) prior to female subject's entry into the study and is the sole partner for that female subject
• In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria

• Subjects receiving corticosteroids within 4 weeks of Screening for treatment of MS. If non-systemic steroids are being used for other chronic inflammatory conditions, subjects may be included at the discretion of the investigator after discussion with the GSK medical monitor
• Use of an b-interferon product, glatiramer acetate or azathioprine within 3 months of Screening, or use of Mitoxantrone within 12 months of Screening. Subjects who have received other therapies affecting the immune system (such as intravenous immunoglobulin (IVIg), cyclophosphamide, plasmapheresis, or any other immunosuppressive or immunomodulatory treatment) in the past may be included on a case by case basis after discussion with the GSK medical monitor. None of these treatments will be allowed during this study
• Previous exposure to alemtuzumab, natalizumab or firategrast administration, bone marrow transplantation or whole body irradiation
• Subjects with a cardiac pacemaker or any other type of metal implant or with any other contraindication for MRI (including known allergy to gadolinium)
• Use of 4-aminopyridine, rosiglitazone, pioglitazone or any drug that is an inhibitor of or a substrate (with a low therapeutic index) for OATP at Screening.
• Subjects with clinically significant renal laboratory values: subjects with a calculated creatinine clearance <60ml/min (by Cockcroft and Gault) at Screening
• Subjects with local urinalysis findings of 1) proteinuria, defined as ≥1+ protein, on urine dipstick or 2) renal tubular cell casts or 3) ≥5 red blood cells / high power field will be excluded from the study if the result is still present on a repeat urinalysis during the screening period.
• Presence of clinically significant hepatic laboratory values: ALT, AST, GGT > 2.0- times the upper limit of normal (ULN); total bilirubin > 1.5 times the ULN at Screening
• CD4 count <500, CD4:CD8 <1.0 (if result still present on a repeat test during the screening period), JC viremia detected in plasma or white cells, idiopathic CD4/CD8 lymphopenia or secondary lymphopenia at Screening
• Any findings on the MRI of the brain at Visit 2 other than MS, except for benign findings that (in the opinion of the central MRI reading site and local site investigator) require no further evaluation or treatment and do not impact patient's neurological health (e.g., small arachnoid cysts, venous angiomas)
• Current or history of cancer, excluding localized non-melanoma skin cancer
• Uncontrolled or any active bacterial, viral, or fungal infection at Screening. Any previous serious infections should be discussed with the GSK medical monitor (e.g. opportunistic or atypical infections)
• History of tuberculosis (TB) or positive chest X-ray for TB at Screening (prior chest X-ray is acceptable if performed within previous 6 months)
• Known congenital or acquired immunodeficiency
• Any abnormality on 12-lead ECG at Screening which is clinically significant in the opinion of the investigator
• Subjects with positive hepatitis B surface antigen, hepatitis C antibody, or HIV tests at Screening
• Women who are lactating, pregnant (positive pregnancy test at Screening), or planning to become pregnant during the course of the study
• Recent history or suspicion of current drug abuse (including analgesic abuse) or alcohol abuse within the last 6 months prior to Screening
• Use of an investigational drug for condition other than MS within 30 days or five half-lives (whichever is longer) preceding Screening. Prior use of an investigational drug for MS should be discussed with the GSK medical monitor
• Any concurrent illness, disability or clinically significant abnormality (including laboratory tests) that may affect the interpretation of clinical efficacy or safety data or prevent the subject from safely completing the assessments required by the protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Camperdown, New South Wales, Australia

GSK Investigational Site

Woodville, South Australia, Australia

GSK Investigational Site

Fitzroy, Victoria, Australia

GSK Investigational Site

Parkville, Victoria, Australia

GSK Investigational Site

Graz, , Austria

GSK Investigational Site

Innsbruck, , Austria

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Gatineau, Quebec, Canada

GSK Investigational Site

Greenfield Park, Quebec, Canada

GSK Investigational Site

Turku, , Finland

GSK Investigational Site

Clermont-Ferrand, , France

GSK Investigational Site

Dijon, , France

GSK Investigational Site

Lille, , France

GSK Investigational Site

Marseille, , France

GSK Investigational Site

Nantes, , France

GSK Investigational Site

Rennes, , France

GSK Investigational Site

Strasbourg, , France

GSK Investigational Site

Neuburg an der Donau, Bavaria, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Herborn, Hesse, Germany

GSK Investigational Site

Achim, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Rostock, Mecklenburg-Vorpommern, Germany

GSK Investigational Site

Bad Honnef, North Rhine-Westphalia, Germany

GSK Investigational Site

Bielefeld, North Rhine-Westphalia, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Düren, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Chieti, Abruzzo, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Gallarate, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Siena, Tuscany, Italy

GSK Investigational Site

's-Hertogenbosch, , Netherlands

GSK Investigational Site

Breda, , Netherlands

GSK Investigational Site

Eindhoven, , Netherlands

GSK Investigational Site

Nieuwegein, , Netherlands

GSK Investigational Site

Sittard-geleen, , Netherlands

GSK Investigational Site

Venray, , Netherlands

GSK Investigational Site

Auckland, , New Zealand

GSK Investigational Site

Christchurch, , New Zealand

GSK Investigational Site

Wellington, , New Zealand

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Drammen, , Norway

GSK Investigational Site

Hamar, , Norway

GSK Investigational Site

Sandnes, , Norway

GSK Investigational Site

Skien, , Norway

GSK Investigational Site

Gdansk, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Poznan, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Barakaldo (Vizcaya), , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

San Sebastián, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Romford, Essex, United Kingdom

GSK Investigational Site

Hartshill, Stoke-on-Trent, , United Kingdom

GSK Investigational Site

Newcastle upon Tyne, , United Kingdom

GSK Investigational Site

Nottingham, , United Kingdom

GSK Investigational Site

Sheffield, , United Kingdom

Countries

Australia; Austria; Canada; Finland; France; Germany; Italy; Netherlands; New Zealand; Norway; Poland; Russia; Spain; United Kingdom

References

Miller DH, Weber T, Grove R, Wardell C, Horrigan J, Graff O, Atkinson G, Dua P, Yousry T, Macmanus D, Montalban X. Firategrast for relapsing remitting multiple sclerosis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2012 Feb;11(2):131-9. doi: 10.1016/S1474-4422(11)70299-X. Epub 2012 Jan 5.

Reference Type: DERIVED

PMID: 22226929 (View on PubMed)

Other Identifiers

A4M105038

Identifier Type: -

Identifier Source: org_study_id