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

NCT01436643 | Terminated Phase 4 Results

• 2 other identifiers: CFTY720DDE062011-001692-39
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 25

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.

Conditions

Depression; Relapsing-remitting Multiple Sclerosis

Keywords

Depression; Multiple Sclerosis; Fingolimod; Venlafaxine; Fluoxetine

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death

  In this analysis patients with all (serious and non-serious) adverse events, and death were reported. See Safety Section.

  21 weeks

Study Arms (3)

Fluoxetine and Fingolimod

EXPERIMENTAL

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

Drug: Fluoxetine; Drug: Fingolimod

Venlafaxine and Fingolimod

EXPERIMENTAL

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

Drug: Venlafaxine; Drug: Fingolimod

Citalopram and Fingolimod

EXPERIMENTAL

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

Drug: Citalopram; Drug: Fingolimod

Interventions

Venlafaxine DRUG

Venlafaxine starting dose was 75 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 150 Mg

Venlafaxine and Fingolimod

Fluoxetine DRUG

Fluoxetine starting dose was 20 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 40 Mg

Fluoxetine and Fingolimod

Citalopram DRUG

Citalopram starting dose was 20 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 40 Mg

Citalopram and Fingolimod

Fingolimod DRUG

Dosage of 0.5 mg per capsule (hard gelatin capsules) was taken p.o. once daily. Fingolimod was supplied in bottles containing 35 capsules each.

Citalopram and Fingolimod; Fluoxetine and Fingolimod; Venlafaxine and Fingolimod

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (25)

Novartis Investigative Site

Altenholz-Stift, Germany, 24161, Germany

Location

Novartis Investigative Site

Achim, 28832, Germany

Location

Novartis Investigative Site

Aschaffenburg, 63739, Germany

Location

Novartis Investigative Site

Bad Honnef, 53604, Germany

Location

Novartis Investigative Site

Baesweiler, 52499, Germany

Location

Novartis Investigative Site

Berlin, 12621, Germany

Location

Novartis Investigative Site

Bielefeld, 33602, Germany

Location

Novartis Investigative Site

Bielefeld, 33647, Germany

Location

Novartis Investigative Site

Bochum, 44787, Germany

Location

Novartis Investigative Site

Bremerhaven, 27574, Germany

Location

Novartis Investigative Site

Butzbach, 35510, Germany

Location

Novartis Investigative Site

Grevenbroich, 41515, Germany

Location

Novartis Investigative Site

Heidenheim, 89518, Germany

Location

Novartis Investigative Site

Klingenmünster, 76889, Germany

Location

Novartis Investigative Site

Leipzig, 04275, Germany

Location

Novartis Investigative Site

Merzig, 66663, Germany

Location

Novartis Investigative Site

Nienburg, 31582, Germany

Location

Novartis Investigative Site

Oberhausen, 46045, Germany

Location

Novartis Investigative Site

Oldenburg, 26122, Germany

Location

Novartis Investigative Site

Potsdam, 14471, Germany

Location

Novartis Investigative Site

Schwalmstadt-Treysa, 34613, Germany

Location

Novartis Investigative Site

Stadtroda, 07646, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Weil am Rhein, 79576, Germany

Location

Novartis Investigative Site

Zwickau, 08060, Germany

Location

MeSH Terms

Conditions

Depression; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Venlafaxine Hydrochloride; Fluoxetine; Citalopram; Fingolimod Hydrochloride

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids; Propylamines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sphingosine; Amino Alcohols; Propylene Glycols; Glycols

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2011
• First Posted: September 20, 2011
• Study Start: November 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 25, 2014
• Results First Posted: September 25, 2014

Record last verified: 2014-09

Locations

DE (25)