A 21-week, Multicenter, Open Label Study to Evaluate the Safety and Tolerability Profile of the Combination of a SSRI or SNRI Antidepressive Therapy With Oral Fingolimod in the Treatment of RRMS Patients With Mild to Moderate Depression
Overview
- Phase
- Phase 4
- Intervention
- Fluoxetine
- Conditions
- Depression
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
- Status
- Terminated
- Last Updated
- 11 years ago
Overview
Brief Summary
This is a prospective, multi-center, open-label study in Relapsing-remitting Multiple Sclerosis (RRMS) patients with mild to moderate depression treated with selected serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) antidepressants over 16 weeks as add-on to fingolimod treatment. It is designed to evaluate the safety and tolerability of this combination in this patient population based on an immunomodulatory treatment with fingolimod.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see Appendix 4)
- •Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix 8)
- •Patients with high disease activity despite treatment with a disease modifying therapy (\> 1 relapse in the previous year, \> 9 hyperintense T2 lesions or \> 1 Gd-enhancing lesion or "non-responding" which could be defined as unchanged or increased relapse rate or ongoing severe relapses compared to previous year)or patients with rapidly evolving severe RRMS (e.g. \> 2 relapses with disease progression in one year and \> 1 Gd-enhancing lesion or with a significant increase in T2 lesions compared to a recent MRI)
- •Depression according to ICD-10 criteria
- •Mild-moderate depression assessed by BDI-II score between 14-28 inclusively measured before study inclusion and before fingolimod is administered
Exclusion Criteria
- •Patients with a history of chronic disease of the immune system other than MS which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome. Patients with Crohns disease or ulcerative colitis are excluded without exception
- •History or presence of malignancy (other than localized basal or squamous cell carcinoma of the skin)
- •Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests
- •Negative for varicella-zoster virus IgG antibodies at Screening
- •Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-β, glatiramer acetate); however no washout is needed for DMDs prior to start of fingolimod
- •Patients who are or have been treated with:
- •immunoglobulins and/or monoclonal antibodies (including natalizumab) within 3 months prior to start of fingolimod
- •Systemically applied corticosteroids or adrenocorticotropic hormones (ACTH) within 1 month prior to start of fingolimod (nevertheless, topical application is permitted);
- •Immunosuppressive medications such as azathioprine or methotrexate, within 3 months prior to start of fingolimod;
- •Cyclophosphamid and mitoxantrone within 6 months prior to start of fingolimod
Arms & Interventions
Fluoxetine and Fingolimod
Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Fluoxetine, supplied in blistered packs containing 20 tablets; starting dose 20 mg; final dose 40 mg
Intervention: Fluoxetine
Fluoxetine and Fingolimod
Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Fluoxetine, supplied in blistered packs containing 20 tablets; starting dose 20 mg; final dose 40 mg
Intervention: Fingolimod
Venlafaxine and Fingolimod
Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Venlafaxine, supplied in blistered packs containing 14 capsules; starting dose 75 mg; final dose 150 mg
Intervention: Venlafaxine
Venlafaxine and Fingolimod
Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Venlafaxine, supplied in blistered packs containing 14 capsules; starting dose 75 mg; final dose 150 mg
Intervention: Fingolimod
Citalopram and Fingolimod
Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Citalopram, supplied in blistered packs containing 20 tablets; starting dose 20 mg, final dose 40 mg
Intervention: Citalopram
Citalopram and Fingolimod
Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Citalopram, supplied in blistered packs containing 20 tablets; starting dose 20 mg, final dose 40 mg
Intervention: Fingolimod
Outcomes
Primary Outcomes
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
Time Frame: 21 weeks
In this analysis patients with all (serious and non-serious) adverse events, and death were reported. See Safety Section.