Clinical trial NCT00395317 (phase 2, status: completed)
Conditions: multiple sclerosis
ICD codes: G35, C81.18
Drugs: firategrast 150 mg, firategrast 300 mg
SMILES: CCOCC1=CC(OC)=C(C(OC)=C1)C1=CC=C(C[C@H](NC(=O)C2=C(F)C=CC=C2F)C(O)=O)C=C1, CCOCC1=CC(OC)=C(C(OC)=C1)C1=CC=C(C[C@H](NC(=O)C2=C(F)C=CC=C2F)C(O)=O)C=C1
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