Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression

Phase 4

Terminated

• Conditions: Depression; Relapsing-remitting Multiple Sclerosis
• Interventions: Drug: Fluoxetine; Drug: Venlafaxine; Drug: Citalopram; Drug: Fingolimod

• Registration Number: NCT01436643
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-16
• Study First Submitted QC: 2011-09-19
• Study First Posted: 2011-09-20
• Study Start: 2011-11
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Status Verified: 2014-09
• Results First Submitted: 2014-09-01
• Results First Submitted QC: 2014-09-24
• Last Update Submitted: 2014-09-24
• Results First Posted: 2014-09-25
• Last Update Posted: 2014-09-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 54

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
• cladribine at any time
• current psychological or pharmacological treatment for depression (MAO inhibitors in particular), a washout period of 1 month prior start of fingolimod is required
• current treatment with linezolid, a washout period of 1 month prior start of fingolimod is required

Other protocol-defined inclusion/exclusion criteria may apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluoxetine and Fingolimod	Fluoxetine	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
Fluoxetine and Fingolimod	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
Venlafaxine and Fingolimod	Venlafaxine	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
Venlafaxine and Fingolimod	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
Citalopram and Fingolimod	Citalopram	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
Citalopram and Fingolimod	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

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death	21 weeks	In this analysis patients with all (serious and non-serious) adverse events, and death were reported.; See Safety Section.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇩🇪 Zwickau, Germany