STudy to vAlidate telemetRic ECG Systems for firsT Dose Administration of Fingolimod (START)

Study Overview
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Brief Summary
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This study evaluated bradycardiac events during first dose observation of fingolimod in MS patients.

Official Title
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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

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: FTY720


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fingolimod<br>Fingolimod 0.5 mg by mouth once daily for 7 days. | Drug: FTY720<br> <br> * Other names: 0.5 mg gelatin capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With 2nd or 3rd Degree Atrioventricular (AV) Block | AV Blocks/Heart block is an abnormal heart rhythm where the heart beats too slowly; the electrical signals that tell the heart to contract are partially intermittent (Type 2:1) or slowed (1st and 2nd degree) or blocked (3rd degree) between the upper chambers (atria) and the lower chambers (ventricles). In 2nd degree AV Blocks, electrical impulses are intermittent (type 2:1) or delayed w/ each subsequent heartbeat (Mobitz type I) until a beat fails to reach the ventricles entirely. This type of block often is physiologic and observed in a highly relaxed state & during sleep. In 2nd degree AV Blocks type II, the atria electrical impulses are unable to reach the ventricles, a more serious condition. In 3rd degree AV Blocks (complete heart block), none of the electrical impulses reach either the atria or the ventricles. Patients can experience simultaneously both types of 2nd or 3rd degree AV Blocks without any symptoms. | baseline, during 6 hour monitoring post first dose observation | 
| Number of Patients With Heart Rate Below 45 Beats Per Minute (BPM) | Number of patients with heart rate below 45 beats bpm in ECG during first dose observation | baseline during 6 hour monitoring post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Prolonged QTc Interval (Friderica) | Number of patients with conduction abnormalities such as QT prolongation, first degree AV block during treatment initiation. The QT interval is a period between the activation and the regeneration of ventricular contraction. A prolonged QT interval can be a potential marker of cardiac arrhythmias. Two patients of the safety analysis set discontinued the study without having received treatment, but safety information was collected on these two patients. | baseline post-dose | 
| Number of Participants With Bradyarrhythmic Electrocardiogram (ECG) Events | The number of participants with bradyarrhythmic electrocardiogram (ECG) events was assessed. Bradyarrhythmic ECG events are defined as QTc Fridericia time > 450 ms for males and > 470 ms for females. | up to day 7 | 
| Number of Patients With Cardiac Adverse Events | The number of participants with the occurrence of subsequent cardiac adverse events (AEs) and serious cardiac AEs during study was assessed. Cardiac events were defined as the following Medical Dictionary for Regulatory Activities (MedDRA) preferred terms: angina pectoris, chest discomfort, dizziness, dyspnoea, dyspnoea exertional, fatigue, palpitations, syncope, vertigo, vertigo positional and vision blurred. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, MS, Fingolimod, Gilenya, ECG, Bradyarrythmia, conduction abnormalities, first dose observation