Combination of Antidepressants and Fingolimod Relapsing-r... | NCT01436643

ID	Type	Description	Link
2011-001692-39	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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

Measure	Description	Time Frame
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

Eligibility Module

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
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

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Altenholz-Stift	Germany	24161	Germany
Novartis Investigative Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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
FG001	Venlafaxine and Fingolimod

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	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
BG001	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
BG002	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
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

The safety set was used for analysis, which consists of 54 patients, of whom 2 patients did not start treatment with any antidepressant

Number

Participants

21 weeks

ID	Title	Description
OG000	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
OG001	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
OG002	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
OG003	Fingolimod	2 Week Pre-treatment Period: Fingolimod 0.5 mg per capsule (hard gelatin capsules) was taken p.o. once during 2 week pre-treatment period.

Units	Counts
Participants	OG00017 OG00115 OG00220 OG003

Title

Denominators

Categories

Any Adverse Event

Title	Measurements
	OG00011 OG00112 OG00212 OG003

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Fingolimod	2 Week Pre-treatment Period: Fingolimod 0.5 mg per capsule (hard gelatin capsules) was taken p.o. once during 2 week pre-treatment period.	1	54	15	54
EG001	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	1	15	12	15
EG002	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	1	20	12	20
EG003	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	0	17	11	17

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
LYMPHOPENIA	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	EG0006 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG0030 affected17 at risk
TACHYCARDIA	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
ASTHENOPIA	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
CONJUNCTIVAL HAEMORRHAGE	Eye disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
CONSTIPATION	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0021 affected20 at risk EG003
DIARRHOEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0021 affected20 at risk EG003
DRY MOUTH	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
GASTROINTESTINAL DISORDER	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
NAUSEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0013 affected15 at risk EG0024 affected20 at risk EG003
TOOTHACHE	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
FATIGUE	General disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
FEELING HOT	General disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
OEDEMA PERIPHERAL	General disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
PAIN	General disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
THIRST	General disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
BRONCHITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
GASTROINTESTINAL INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
INFLUENZA	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
NASOPHARYNGITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected54 at risk EG0011 affected15 at risk EG0021 affected20 at risk EG003
RHINITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
TONSILLITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
CONTUSION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
FALL	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
BLOOD BILIRUBIN INCREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
ELECTROCARDIOGRAM ABNORMAL	Investigations	MedDRA	Systematic Assessment	EG0001 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
LABORATORY TEST ABNORMAL	Investigations	MedDRA	Systematic Assessment	EG0001 affected54 at risk EG0011 affected15 at risk EG0021 affected20 at risk EG003
WEIGHT DECREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
ARTHRITIS	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
SKIN PAPILLOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
DIZZINESS	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0021 affected20 at risk EG003
DYSGEUSIA	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
HEADACHE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected54 at risk EG0011 affected15 at risk EG0021 affected20 at risk EG003
HYPOAESTHESIA	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
LOSS OF CONSCIOUSNESS	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
MULTIPLE SCLEROSIS RELAPSE	Nervous system disorders	MedDRA	Systematic Assessment	EG0002 affected54 at risk EG0012 affected15 at risk EG0020 affected20 at risk EG003
OPTIC NEURITIS	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
PAROSMIA	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
SEDATION	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
SOMNOLENCE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
TREMOR	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
AGITATION	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
INSOMNIA	Psychiatric disorders	MedDRA	Systematic Assessment	EG0001 affected54 at risk EG0012 affected15 at risk EG0020 affected20 at risk EG003
LIBIDO DISORDER	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
SLEEP DISORDER	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
EJACULATION DISORDER	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
METRORRHAGIA	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
HICCUPS	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
RHINITIS ALLERGIC	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
YAWNING	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
ALOPECIA	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
DERMATITIS ALLERGIC	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG003
ERYTHEMA	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0012 affected15 at risk EG0020 affected20 at risk EG003
SKIN LESION	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003
FLUSHING	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003

ID	Term
D003863	Depression
D020529	Multiple Sclerosis, Relapsing-Remitting
D009103	Multiple Sclerosis

ID	Term
D001526	Behavioral Symptoms
D001519	Behavior
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D000069470	Venlafaxine Hydrochloride
D005473	Fluoxetine
D015283	Citalopram
D000068876	Fingolimod Hydrochloride

ID	Term
D003511	Cyclohexanols
D000441	Hexanols
D005233	Fatty Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D010627	Phenethylamines
D005021	Ethylamines
D000588	Amines
D003510	Cyclohexanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D008055	Lipids
D011437	Propylamines
D009570	Nitriles
D001572	Benzofurans
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D013110	Sphingosine
D000605	Amino Alcohols
D011409	Propylene Glycols
D006018	Glycols

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
CEREBRAL HAEMORRHAGE	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected54 at risk EG0010 affected15 at risk EG0020 affected20 at risk EG0030 affected17 at risk
MULTIPLE SCLEROSIS RELAPSE	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0011 affected15 at risk EG0020 affected20 at risk EG003
SUICIDAL IDEATION	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected54 at risk EG0010 affected15 at risk EG0021 affected20 at risk EG003