Clinical trial NCT01585298: STudy to vAlidate telemetRic ECG Systems for firsT Dose Administration of Fingolimod (START)
Official title: A 1-week, Open-label, Multi-center Study to Explore Conduction Abnormalities During First Dose Administration of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
MS
Fingolimod
Gilenya
ECG
Bradyarrythmia
conduction abnormalities
first dose observation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-04-25
Enrollment: 6998
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluated bradycardiac events during first dose observation of fingolimod in MS patients.


Eligibility criteria: Key Inclusion Criteria:

* Subjects with relapsing remitting MS.
* Patients with highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy.
* Patients who had been previously on 2nd line therapies. It was understood that these patients satisfied the above mentioned criteria listed under a. in the past.

This also included patients, who were previously treated with fingolimod (regardless of whether or not they had already been treated within the START study) but discontinued treatment due to medical reasons.

- 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).

Key Exclusion Criteria:

* immunocompromised patients
* active infections
* pregnant or nursing women, women of childbearing potential unless using 2 reliable forms of contraception
* presence of malignancy (other than localized basal cell carcinoma of the skin).

Primary outcomes:
measure: Participants With 2nd or 3rd Degree Atrioventricular (AV) Block
timeFrame: baseline, during 6 hour monitoring post first dose observation
measure: Number of Patients With Heart Rate Below 45 Beats Per Minute (BPM)
timeFrame: baseline during 6 hour monitoring post dose
Secondary outcomes:
measure: Number of Participants With Prolonged QTc Interval (Friderica)
timeFrame: baseline post-dose
measure: Number of Participants With Bradyarrhythmic Electrocardiogram (ECG) Events
timeFrame: up to day 7
measure: Number of Patients With Cardiac Adverse Events
timeFrame: 7 days
Other outcomes:
Locations:
city: Ostfildern
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Munich
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Flensburg
country: Germany
facility: Novartis Investigative Site
state: Schleswig Holstein
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Aalen-Wasseralfingen
country: Germany
facility: Novartis Investigative Site
city: Aalen
country: Germany
facility: Novartis Investigative Site
city: Abensberg
country: Germany
facility: Novartis Investigative Site
city: Achim
country: Germany
facility: Novartis Investigative Site
city: Aichach
country: Germany
facility: Novartis Investigative Site
city: Altenburg
country: Germany
facility: Novartis Investigative Site
city: Altenholz-Stift
country: Germany
facility: Novartis Investigative Site
city: Alzenau
country: Germany
facility: Novartis Investigative Site
city: Andernach
country: Germany
facility: Novartis Investigative Site
city: Asbach
country: Germany
facility: Novartis Investigative Site
city: Aschaffenburg
country: Germany
facility: Novartis Investigative Site
city: Augsburg
country: Germany
facility: Novartis Investigative Site
city: Bad Berka
country: Germany
facility: Novartis Investigative Site
city: Bad Hersfeld
country: Germany
facility: Novartis Investigative Site
city: Bad Homburg
country: Germany
facility: Novartis Investigative Site
city: Bad Honnef
country: Germany
facility: Novartis Investigative Site
city: Bad Krozingen
country: Germany
facility: Novartis Investigative Site
city: Bad Mergentheim
country: Germany
facility: Novartis Investigative Site
city: Bad Saarow
country: Germany
facility: Novartis Investigative Site
city: Bad Wildbad
country: Germany
facility: Novartis Investigative Site
city: Bamberg
country: Germany
facility: Novartis Investigative Site
city: Bayreuth
country: Germany
facility: Novartis Investigative Site
city: Bergisch Gladbach
country: Germany
facility: Novartis Investigative Site
city: Berg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
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facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
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facility: Novartis Investigative Site
city: Berlin
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facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Boblingen
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bogen
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Borna
country: Germany
facility: Novartis Investigative Site
city: Bottrop
country: Germany
facility: Novartis Investigative Site
city: Braunschweig
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facility: Novartis Investigative Site
city: Braunschweig
country: Germany
facility: Novartis Investigative Site
city: Bremen
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facility: Novartis Investigative Site
city: Bruchsal
country: Germany
facility: Novartis Investigative Site
city: Buchholz in der Nordheide
country: Germany
facility: Novartis Investigative Site
city: Buchholz
country: Germany
facility: Novartis Investigative Site
city: Butzbach
country: Germany
facility: Novartis Investigative Site
city: Celle
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Delbrueck
country: Germany
facility: Novartis Investigative Site
city: Dessau
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facility: Novartis Investigative Site
city: Dillingen
country: Germany
facility: Novartis Investigative Site
city: Dillingen
country: Germany
facility: Novartis Investigative Site
city: Dortmund
country: Germany
facility: Novartis Investigative Site
city: Dortmund
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Düren
country: Germany
facility: Novartis Investigative Site
city: Düsseldorf
country: Germany
facility: Novartis Investigative Site
city: Düsseldorf
country: Germany
facility: Novartis Investigative Site
city: Eberswalde
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facility: Novartis Investigative Site
city: Eisenach
country: Germany
facility: Novartis Investigative Site
city: Eltville
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facility: Novartis Investigative Site
city: Emden
country: Germany
facility: Novartis Investigative Site
city: Emmendingen
country: Germany
facility: Novartis Investigative Site
city: Erbach
country: Germany
facility: Novartis Investigative Site
city: Erfurt
country: Germany
facility: Novartis Investigative Site
city: Erfurt
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Eschwege
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Essen
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facility: Novartis Investigative Site
city: Essen
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facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
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city: Frankfurt
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facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Freiburg
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facility: Novartis Investigative Site
city: Friedrichshafen
country: Germany
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city: Fulda
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city: Fulda
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facility: Novartis Investigative Site
city: Geldern
country: Germany
facility: Novartis Investigative Site
city: Gelnhausen
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facility: Novartis Investigative Site
city: Gelsenkirchen
country: Germany
facility: Novartis Investigative Site
city: Gilching
country: Germany
facility: Novartis Investigative Site
city: Gladenbach
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Greifswald
country: Germany
facility: Novartis Investigative Site
city: Grevenbroich
country: Germany
facility: Novartis Investigative Site
city: Griesheim
country: Germany
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city: Guetersloh
country: Germany
facility: Novartis Investigative Site
city: Gummersbach
country: Germany
facility: Novartis Investigative Site
city: Göttingen
country: Germany
facility: Novartis Investigative Site
city: Haar
country: Germany
facility: Novartis Investigative Site
city: Hagen
country: Germany
facility: Novartis Investigative Site
city: Halle (Saale)
country: Germany
facility: Novartis Investigative Site
city: Halle S
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
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city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Heidenheim
country: Germany
facility: Novartis Investigative Site
city: Herdecke
country: Germany
facility: Novartis Investigative Site
city: Herford
country: Germany
facility: Novartis Investigative Site
city: Herford
country: Germany
facility: Novartis Investigative Site
city: Hildesheim
country: Germany
facility: Novartis Investigative Site
city: Homburg
country: Germany
facility: Novartis Investigative Site
city: Hoppegarten
country: Germany
facility: Novartis Investigative Site
city: Ibbenbueren
country: Germany
facility: Novartis Investigative Site
city: Idar-Oberstein
country: Germany
facility: Novartis Investigative Site
city: Isselburg-Anholt
country: Germany
facility: Novartis Investigative Site
city: Itzehoe
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Jena
country: Germany
facility: Novartis Investigative Site
city: Juelich
country: Germany
facility: Novartis Investigative Site
city: Kaiserslautern
country: Germany
facility: Novartis Investigative Site
city: Kaltenkirchen
country: Germany
facility: Novartis Investigative Site
city: Kandel
country: Germany
facility: Novartis Investigative Site
city: Karlstadt
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Klingenmünster
country: Germany
facility: Novartis Investigative Site
city: Koeln-Longerich
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Koln
country: Germany
facility: Novartis Investigative Site
city: Korbach
country: Germany
facility: Novartis Investigative Site
city: Krefeld
country: Germany
facility: Novartis Investigative Site
city: Krefeld
country: Germany
facility: Novartis Investigative Site
city: Köln
country: Germany
facility: Novartis Investigative Site
city: Königsbrück
country: Germany
facility: Novartis Investigative Site
city: Landshut
country: Germany
facility: Novartis Investigative Site
city: Lappersdorf
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Leverkusen
country: Germany
facility: Novartis Investigative Site
city: Lohr am Main
country: Germany
facility: Novartis Investigative Site
city: Lubeck
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis Investigative Site
city: Luenen
country: Germany
facility: Novartis Investigative Site
city: Luneburg
country: Germany
facility: Novartis Investigative Site
city: Lutherstadt Eisleben
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Meisenheim
country: Germany
facility: Novartis Investigative Site
city: Minden
country: Germany
facility: Novartis Investigative Site
city: Minden
country: Germany
facility: Novartis Investigative Site
city: Mittweida
country: Germany
facility: Novartis Investigative Site
city: Mosbach
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Mönchengladbach
country: Germany
facility: Novartis Investigative Site
city: Mönchengladbach
country: Germany
facility: Novartis Investigative Site
city: Mülheim
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Münster
country: Germany
facility: Novartis Investigative Site
city: Nagold
country: Germany
facility: Novartis Investigative Site
city: Naumburg
country: Germany
facility: Novartis Investigative Site
city: Neu-Ulm
country: Germany
facility: Novartis Investigative Site
city: Neuburg an der Donau
country: Germany
facility: Novartis Investigative Site
city: Neuruppin
country: Germany
facility: Novartis Investigative Site
city: Neusaess
country: Germany
facility: Novartis Investigative Site
city: Neustadt An Der Weinstraße
country: Germany
facility: Novartis Investigative Site
city: Nordhausen
country: Germany
facility: Novartis Investigative Site
city: Nürnberg
country: Germany
facility: Novartis Investigative Site
city: Offenbach
country: Germany
facility: Novartis Investigative Site
city: Oldenburg I. Holstein
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Osnabrueck
country: Germany
facility: Novartis Investigative Site
city: Osnabrück
country: Germany
facility: Novartis Investigative Site
city: Osnabrück
country: Germany
facility: Novartis Investigative Site
city: Osnabrück
country: Germany
facility: Novartis Investigative Site
city: Paderborn
country: Germany
facility: Novartis Investigative Site
city: Papenburg
country: Germany
facility: Novartis Investigative Site
city: Pforzheim
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Prien
country: Germany
facility: Novartis Investigative Site
city: Quakenbrueck
country: Germany
facility: Novartis Investigative Site
city: Querfurt
country: Germany
facility: Novartis Investigative Site
city: Ravensburg
country: Germany
facility: Novartis Investigative Site
city: Recklinghausen
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Remscheid
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Rüdersdorf
country: Germany
facility: Novartis Investigative Site
city: Saarbruecken
country: Germany
facility: Novartis Investigative Site
city: Saint Ingbert
country: Germany
facility: Novartis Investigative Site
city: Sande
country: Germany
facility: Novartis Investigative Site
city: Schwalmstadt-Treysa
country: Germany
facility: Novartis Investigative Site
city: Schwerin
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Singen
country: Germany
facility: Novartis Investigative Site
city: Sinsheim
country: Germany
facility: Novartis Investigative Site
city: Solingen
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis Investigative Site
city: Stadtroda
country: Germany
facility: Novartis Investigative Site
city: Stralsund
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Telgte
country: Germany
facility: Novartis Investigative Site
city: Teupitz
country: Germany
facility: Novartis Investigative Site
city: Troisdorf
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Unterhaching
country: Germany
facility: Novartis Investigative Site
city: Wasserburg
country: Germany
facility: Novartis Investigative Site
city: Wendlingen
country: Germany
facility: Novartis Investigative Site
city: Wermsdorf
country: Germany
facility: Novartis Investigative Site
city: Westerstede/Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Westerstede
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Wolfratshausen
country: Germany
facility: Novartis Investigative Site
city: Wuppertal
country: Germany
facility: Novartis Investigative Site
city: Wuppertal
country: Germany
facility: Novartis Investigative Site
city: Würzburg
country: Germany
facility: Novartis Investigative Site
city: Würzburg
country: Germany
facility: Novartis Investigative Site
city: Zwickau
country: Germany
facility: Novartis Investigative Site
city: Öhringen
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Limmroth V, Ziemssen T, Lang M, Richter S, Wagner B, Haas J, Schmidt S, Gerbershagen K, Lassek C, Klotz L, Hoffmann O, Albert C, Schuh K, Baier-Ebert M, Wendt G, Schieb H, Hoyer S, Dechend R, Haverkamp W. Electrocardiographic assessments and cardiac events after fingolimod first dose - a comprehensive monitoring study. BMC Neurol. 2017 Jan 18;17(1):11. doi: 10.1186/s12883-016-0789-7.