A Phase 4 interventional study of FTY720 in Multiple Sclerosis, sponsored by Novartis Pharmaceuticals. Completed at 258 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-09-23.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 4, Interventional, and Treatment
This study evaluated bradycardiac events during first dose observation of fingolimod in MS patients.
3,524 studies on the registry are indexed under Multiple Sclerosis; 668 are open to participants now.
This study's enrollment of 6,998 is above the median of 50 across 2,386 interventional studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →Novartis Pharmaceuticals is the lead sponsor of 2,711 studies on the registry; 218 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 435 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
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:
Fingolimod 0.5 mg by mouth once daily for 7 days.
Drug: FTY720
Also known as: 0.5 mg gelatin capsules
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.
Time frame: 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
Time frame: baseline during 6 hour monitoring post dose
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.
Time frame: 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.
Time frame: 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.
Time frame: 7 days
| Milestone | Fingolimod |
|---|---|
| Started | 6998 |
| Completed | 6961 |
| Not completed | 37 |
| Withdrew: Study completion was not documented. | 1 |
| Withdrew: Protocol deviation | 1 |
| Withdrew: Administrative problems | 4 |
| Withdrew: Lost to follow-up | 2 |
| Withdrew: Withdrawal by subject | 4 |
| Withdrew: Abnormal test procedure results | 1 |
| Withdrew: Adverse event | 24 |
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.
| Participants | Fingolimod |
|---|---|
| Any AV block ll degree or higher | 120 |
| AV block ll degree: Mobitz type I degree | 117 |
| AV block II degree: Mobitz type II degree | 0 |
| AV block II degree: 2:1 | 43 |
| AV block III degree | 1 |
Number of patients with heart rate below 45 beats bpm in ECG during first dose observation
| Participants | Fingolimod |
|---|---|
| Number of Patients With Heart Rate Below 45 Beats Per Minute (BPM) | 63 |
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.
| Participants | Fingolimod |
|---|---|
| Female, QTcFridericia Interval > 470 ms | 7 |
| Male, QTcF Interval > 450 ms | 6 |
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.
| Participants | Fingolimod |
|---|---|
| Number of Participants With Bradyarrhythmic Electrocardiogram (ECG) Events | 26 |
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.
| Participants | Fingolimod |
|---|---|
| Cardiac events | 489 |
| Serious cardiac AEs | 9 |
Collected over Adverse events (AEs) were collected for each patient from first administration of study drug until end of study visit, usually for one week. Furthermore, serious suspected adverse drug reactions (SADRs) had to be documented until 6 weeks after the patient has stopped study participation.. Non-serious events are listed at a 0.0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fingolimod | — | 160/6,998 (2.3%) | 2,179/6,998 (31.1%) |
| Event | Fingolimod |
|---|---|
| Atrioventricular block second degreeCardiac disorders | 49/6998 |
| Multiple sclerosis relapseNervous system disorders | 26/6998 |
| BradycardiaCardiac disorders | 24/6998 |
| Electrocardiogram QT prolongedInvestigations | 4/6998 |
| Heart rate decreasedInvestigations | 4/6998 |
| Atrial fibrillationCardiac disorders | 3/6998 |
| DizzinessNervous system disorders | 3/6998 |
| Optic neuritisNervous system disorders | 3/6998 |
| HypertensionVascular disorders | 3/6998 |
| Coronary artery diseaseCardiac disorders | 2/6998 |
| Event | Fingolimod |
|---|---|
| HeadacheNervous system disorders | 316/6998 |
| FatigueGeneral disorders | 227/6998 |
| NauseaGastrointestinal disorders | 143/6998 |
| NasopharyngitisInfections and infestations | 137/6998 |
| DizzinessNervous system disorders | 126/6998 |
| LymphopeniaBlood and lymphatic system disorders | 119/6998 |
| Atrioventricular block first degreeCardiac disorders | 116/6998 |
| DiarrhoeaGastrointestinal disorders | 96/6998 |
| Atrioventricular block second degreeCardiac disorders | 74/6998 |
| Multiple sclerosis relapseNervous system disorders | 70/6998 |
| Age, Continuous(Years) | Fingolimod |
|---|---|
| Mean | 39.2 ± 10.52 |
| Sex: Female, Male(Participants) | Fingolimod |
|---|---|
| Female | 4924 |
| Male | 2074 |
Showing the first 100 of 258 sites.
Ran from Apr 2012 to primary completion in Dec 2016, 55 months.
Results were first posted in Sep 2019, 2 years 9 months after primary completion.
Of 44 industry-sponsored phase 4 interventional studies under Multiple Sclerosis, half reached primary completion within 28 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 37. This study's 55 months is above that.
Counting every sponsor, half of 80 studies reached it within 33 months; a quarter within 19 and three quarters within 59.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Aug 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Fingolimod