A study to explore heart function during first dose administration of fingolimod in patients with relapsing-remitting multiple sclerosis

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2012-000653-32-DE
• Date of registration: 12/04/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: A study to explore heart function during first dose administration of fingolimod in patients with relapsing-remitting multiple sclerosis
• Scientific 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 (START) - START
• Date of first enrolment: 27/06/2012
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000653-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent from patients capable of giving or withholding full informed consent must be obtained before any assessment is performed.
2. Subjects with relapsing remitting MS
3.
a. Patients with highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy.
b. Patients who were previously on 2nd line therapies. It is understood that these patients satisfied the above mentioned criteria listed under a. in the past. This also includes patients, who were previously treated with Fingolimod (regardless of whether or not they had already been treated within START study) but discontinued treatment due to medical reasons.
4. 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).
5. Male or female aged 18 years or older at Screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7000
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Known immunodeficiency syndrome.
2. Patients with increased risk for opportunistic infections, including immunocompromised patients (including those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies).
3. Severe active infections, active chronic infections (hepatitis, tuberculosis).
4. Presence of malignancy (other than localized basal cell carcinoma of the skin).
5. Negative for varicella-zoster virus IgG antibodies at Screening
6. Patients with severe hepatic dysfunction (Child-Pugh-Class C)
7. Patients with the following cardiovascular conditions
• Patients receiving antiarrythmics class Ia (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol) or beta blockers
• Patients receiving heart rate lowering calcium channel blockers (e.g. verapamil, diltiazem or ivabradine) or other substances which may decrease heart rate (e.g. digoxin, anticholinesteratic agents or pilocarpine).
• 2nd degree Mobitz Type II or higher degree AV block, Sick-sinus syndrome, or Sino-atrial heart block
• Significant QT prolongation (QTc>470 msec (female) or >450 msec (males))
• History of symptomatic bradycardia or recurrent syncope, known ischaemic heart disease (including angina pectoris), cerebrovascular disease, history of myocardial infarction, hypokalaemia, congestive heart failure, history of cardiac arrest, uncontrolled hypertension, or severe sleep apnea
8. Patients with calculated GFR> 30 ml/min
9. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5mIU/ml).
Women of child-bearing potential defined as all women physiologically capable of becoming pregnant, UNLESS they are using a reliable method of contraception according to the label during the study and for 2 months after stopping treatment. At the discretion of the investigator, total abstinence from sexual intercourse is acceptable in cases where the age, career, lifestyle, or sexual orientation of the patient ensures the prevention of pregnancy.

Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to baseline. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

10. History of hypersensitivity to the active substance or to any other of the excipients of the study drugs.
11. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Conduction abnormalities in patients with relapsing-remitting multiple sclerosis
MedDRA version: 18.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Gilenya
Product Name: Fingolimod
Product Code: FTY720
Pharmaceutical Form: Capsule, hard
CAS Number: 162359-56-0
Current Sponsor code: FTY720
Other descriptive name: Fingolimod Hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Primary Outcome(s)

Main Objective: To evaluate the incidence of patients with bradycardia (heart rate < 45 beats per min) and bradyarrhythmic ECG events during 6-hour monitoring period as measured by heart rate and second and third-degree AV blocks after treatment initiation of fingolimod 0.5 mg.

Secondary Objective: • To evaluate the incidence of patients with other conduction abnormalities (such as QT prolongation, first degree AV block) after treatment initiation of fingolimod 0.5 mg.
• Investigate the occurrence of subsequent cardiac AEs and serious cardiac AEs during the study.

Primary end point(s): To evaluate the incidence of patients with bradycardia (heart rate < 45 beats per min) and bradyarrhythmic ECG events during 6-hour monitoring period as measured by heart rate and second and third-degree AV blocks after treatment initiation of fingolimod 0.5 mg.

Timepoint(s) of evaluation of this end point: after 6 h

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: after 7 days

Secondary end point(s): • To evaluate the incidence of patients with other conduction abnormalities (such as QT prolongation, first degree AV block) after treatment initiation of fingolimod 0.5 mg.
• Investigate the occurrence of subsequent cardiac AEs and serious cardiac AEs during the study

Secondary ID(s)

CFTY720DDE17

Source(s) of Monetary Support

Novartis Pharma GmbH