Effect of Physical ACtivity in Fingolimod Treated patiEnt... | NCT01490840

ID	Type	Description	Link
2011-002969-38	EudraCT Number

Status Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
E-training	Experimental	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.	Other: Physical exercise
Waiting	Experimental	Fingolimod as baseline immunomodulatory multiple sclerosis treatment is prescribed as per clinical practice. During Phase 1, participants randomized to this arm did not receive e-training exercise. After a 6 months waiting period, phase 2, participants had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day.	Other: Physical exercise

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Physical exercise	Other	Strength training exercises are performed against own body weight or with training aids like elastic rubber bands or gym balls. All exercises are home-based. To increase balance and core stability, a subset of exercises is performed on shaky ground and/or one-legged. Exercise intensity, duration and frequency are individually assigned by a sports therapist. For each muscle group, a set of exercises of increasing difficulty allows for individual and progressive training adaption. Therapists can choose from an exercise database of approximately 150 different strength exercises with different graduation.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fatigue as Measured by the Modified Fatigue Impact Scale (mFIS ).	The mFIS provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. It is a 21-item, structured, self-report questionnaire that generally can be completed with little or no intervention from an interviewer. The mFIS score ranged from 0 (not tired) to 84 (tired). A negative change from baseline indicates improvement.	Baseline, 6 months

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Isometric and Dynamic Muscular Strength as Measured by Sit-to-stand Test	The Sit to Stand Test is a functional outcome measure of the lower-extremity muscle power. The test was performed 3 times with one minute rest in between. The best attempt out of three was used for the analysis. A positive change from baseline indicates improvement.	baseline, 6 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria
Patients with Expanded Disability Status Scale (EDSS) score of 0-3.5 (including)
Immunomodulatory treatment with prescribed fingolimod for at least one month prior to baseline
Fatigue score assessed by mFIS of equal or greater than 14 at screening
Neurologically stable with no evidence of relapse within 30 days prior to inclusion date

Exclusion Criteria:

Patients who have been treated with:
- systemic corticosteroids or immunoglobulins within 1 month prior to randomization;
- immunosuppressive medications such as azathioprine, cyclophosphamide, or methotrexate within 3 months prior to randomization;
- monoclonal antibodies (including natalizumab) within 3 months prior to randomization;
- mitoxantrone within 6 months prior to randomization
- cladribine at any time.
Patients with any medically unstable condition, as assessed by the primary treating physician at each site.
Patients with any of the following cardiovascular conditions :
- history of cardiac arrest;
- history of myocardial infarction or with current unstable ischemic heart disease;
- history of angina pectoris due to coronary spasm or history of Raynaud syndrome
- Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the investigator;
- history or presence of a second-degree AV block, Type II or a third-degree AV
- block
- patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or
- III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide,
- dofelitide);
- proven history of sick sinus syndrome or sino-atrial heart block;
- uncontrolled hypertension
Clinically relevant internal disease (e.g. uncorrected anemia) or orthopedic diseases (e.g. scoliosis) that might interfere with physical training
Any severe disability or clinical impairment that can prevent the patient to meet all study requirements at the investigator's discretion

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		Dortmund	Germany	44135	Germany
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29479457	Derived	Maurer M, Schuh K, Seibert S, Baier M, Hentschke C, Streber R, Tallner A, Pfeifer K. A randomized study to evaluate the effect of exercise on fatigue in people with relapsing-remitting multiple sclerosis treated with fingolimod. Mult Scler J Exp Transl Clin. 2018 Feb 14;4(1):2055217318756688. doi: 10.1177/2055217318756688. eCollection 2018 Jan-Mar.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.
BG001	Waiting	Fingolimod as baseline immunomodulatory multiple sclerosis treatment is prescribed as per clinical practice. During Phase 1, participants randomized to this arm did not receive e-training exercise. After a 6 month waiting period, phase 2, participants had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day.
BG002	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

Change From Baseline in Fatigue as Measured by the Modified Fatigue Impact Scale (mFIS ).

The mFIS provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. It is a 21-item, structured, self-report questionnaire that generally can be completed with little or no intervention from an interviewer. The mFIS score ranged from 0 (not tired) to 84 (tired). A negative change from baseline indicates improvement.

Modified Full Analysis Set (ModFAS): The ModFAS included participants with sufficient e-training compliance.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.
OG001	Waiting	Fingolimod as baseline immunomodulatory multiple sclerosis treatment is prescribed as per clinical practice. During Phase 1, participants randomized to this arm did not receive e-training exercise. After a 6 month waiting period, phase 2, participants had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day.

Units	Counts
Participants	OG00056 OG00183

Title

Denominators

Categories

Title	Measurements
	OG000-3.57± 11.3(-6.81 to -0.34) OG001-2.10± 12.1(-4.69 to 0.49)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.4579		Mean Difference (Net)	-1.47			2-Sided	95	-5.39	2.44				Yes	Non-Inferiority or Equivalence	A sample size of 90 in each group would have 80% power to detect a difference in means of 3.8, assuming that the common standard deviation is 9.05, using a two group t-test with a 0.05 2-sided significance level.

Secondary

Change From Baseline in Isometric and Dynamic Muscular Strength as Measured by Sit-to-stand Test

The Sit to Stand Test is a functional outcome measure of the lower-extremity muscle power. The test was performed 3 times with one minute rest in between. The best attempt out of three was used for the analysis. A positive change from baseline indicates improvement.

The ModFAS, which included participants with sufficient e-training compliance, was considered for the analysis. Only participants with both baseline and month 6 values were analyzed.

Posted

Least Squares Mean

95% Confidence Interval

watt/kilogram body weight

baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.
OG001	Waiting

Secondary

Change From Baseline in Isometric and Dynamic Muscular Strength as Measured by Change in Leg Strength and Trunk Strength

Isometric and dynamic muscular strength was measured by an Isomed 2000 isometric measurement device (knee flexion/tension, trunk flexion/extension).

Isomed 2000 device measures muscular flexion and tension under standardized training conditions. A positive change from baseline indicates improvement.

Modified Full Analysis Set (ModFAS): The ModFAS included participants with sufficient e-training compliance.

Posted

Least Squares Mean

95% Confidence Interval

newton meter

baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.
OG001	Waiting

Secondary

Change From Baseline in Isometric and Dynamic Muscular Strength as Measured by Leg Strength Endurance

Isometric and dynamic muscular strength was measured by an Isomed 2000 isometric measurement device (knee flexion/tension, trunk flexion/extension).

Isomed 2000 device measures muscular flexion and tension under standardized training conditions. A positive change from baseline indicates improvement.

Modified Full Analysis Set (ModFAS): The ModFAS included participants with sufficient e-training compliance.

Posted

Least Squares Mean

95% Confidence Interval

joule

baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.
OG001	Waiting

Secondary

Change From Baseline in Quality of Life as Measured by the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS)

The Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) consists of 44 items, 28 of which are the basis for computation of five subscale scores reflecting major dimensions of health-related quality of life (HRQoL) in MS: Fatigue/Thinking (4 items), Mobility lower limb (5 items), Mobility upper limb (5 items), Social function (6 items) and Mood (eight items). Subscales and total score range from 1 to 5, with high scores indicating a lower quality of life. In this study, the total score and following 3 subscales: fatigue/thinking, mobility lower limb and mobility upper limb only were analyzed. A negative change from baseline indicates improvement.

Modified Full Analysis Set (ModFAS): The ModFAS included participants with sufficient e-training compliance.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline, 6 months, 12 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.

Secondary

Change From Baseline in Fatigue as Measured by the WEIMuS (Würzburg Fatigue Inventory for MS)

The WEIMuS (Würzburg Fatigue Inventory for MS) scale is a validated self-assessment instrument to quantify the degree of fatigue. The scale consists of 17 items with 5 categories that are scored from '0' to '4'. The subscores for cognitive and physical fatigue range from 0 to 36 and from 0 to 32, respectively, with the total sum score ranging from 0 to 68; higher scores indicate higher degrees of fatigue. A negative change from baseline indicates improvement.

Modified Full Analysis Set (ModFAS): The ModFAS included participants with sufficient e-training compliance.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.

Secondary

Change From Baseline in Depression as Measured by the Beck Depression Inventory Second Edition (BDI-II)

The Beck Depression Inventory Second Edition (BDI-II) is a 21-item self-report instrument intended to assess the existence and severity of symptoms of depression as listed in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. Each of the 21 items corresponding to a symptom of depression is summed to give a single score for the BDI-II. There is a four-point scale for each item ranging from 0 to 3. The total score ranges from 0 - 63. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. A negative change from baseline indicates improvement.

Modified Full Analysis Set (ModFAS): The ModFAS included participants with sufficient e-training compliance.

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.

Secondary

Change From Baseline in Aerobic Capacity (VO2max) as Measured by a Physical Endurance Spiroergometry on a Treadmill

Physical endurance spiroergometry was accomplished. Ergometry was assessed according to national guidelines of the German society for sports medicine. Ergometry is a combined examination of circulation and lung function and was performed as a submaximal or maximal test depending on the participant's individual performance. A negative change from baseline indicates improvement.

Modified Full Analysis Set (ModFAS): The ModFAS included participants with sufficient e-training compliance.

Posted

Least Squares Mean

95% Confidence Interval

[ml/min/kg][watt/kg body weight]

Baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.

Secondary

Change From Baseline in Peak Expiratory Flow as Measured by a Physical Endurance Spiroergometry on a Treadmill

Physical endurance spiroergometry was accomplished. Ergometry was assessed according to national guidelines of the German society for sports medicine. Ergometry is a combined examination of circulation and lung function and was performed as a submaximal or maximal test depending on the participant's individual performance. A positive change from baseline indicates improvement.

The ModFAS, which included participants with sufficient e-training compliance, was considered for the analysis. Only participants with both baseline and month 6 values were analyzed.

Posted

Least Squares Mean

95% Confidence Interval

L/s

Baseline, 6 months

ID	Title	Description
OG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	E-training	Fingolimod as baseline immunomodulatory multiple sclerosis treatment was prescribed as per clinical practice. During phase 1, participants randomized to this arm had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day. After 6 months, Phase 2, the same Phase 1 regimen applied.			5	94	58	94
EG001	Waiting	Fingolimod as baseline immunomodulatory multiple sclerosis treatment is prescribed as per clinical practice. During Phase 1, participants randomized to this arm did not receive e-training exercise. After a 6 month waiting period, phase 2, participants had an introductory group session, hosted by a sports therapist. The individual training schedule was comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants documented each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis was allowed for treatment of relapses as clinically warranted. Steroid treatment consisted of 3-5 days and up to 1,000 mg methylprednisolone/day.			9	84	59	84

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ARRHYTHMIA	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
EXTRASYSTOLES	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
PALPITATIONS	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
APPENDICITIS PERFORATED	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
CONJUNCTIVITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
BONE CONTUSION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
CONCUSSION	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
DISLOCATION OF VERTEBRA	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0010 affected84 at risk
RADIUS FRACTURE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0010 affected84 at risk
SPINAL FRACTURE	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0011 affected84 at risk
GAMMA-GLUTAMYLTRANSFERASE INCREASED	Investigations	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
INTERVERTEBRAL DISC PROTRUSION	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0010 affected84 at risk
ASTROCYTOMA, LOW GRADE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
UTERINE LEIOMYOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
EPILEPSY	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0010 affected84 at risk
GENERALISED TONIC-CLONIC SEIZURE	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk
HEMIPARESIS	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0010 affected84 at risk
ISCHAEMIC CEREBRAL INFARCTION	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0010 affected84 at risk
MUSCLE SPASTICITY	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected94 at risk EG0010 affected84 at risk
MENORRHAGIA	Reproductive system and breast disorders	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0011 affected84 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
DIARRHOEA	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0005 affected94 at risk EG0012 affected84 at risk
BRONCHITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected94 at risk EG0018 affected84 at risk
NASOPHARYNGITIS	Infections and infestations	MedDRA	Systematic Assessment	EG00034 affected94 at risk EG00133 affected84 at risk
ORAL HERPES	Infections and infestations	MedDRA	Systematic Assessment	EG0006 affected94 at risk EG0012 affected84 at risk
SINUSITIS	Infections and infestations	MedDRA	Systematic Assessment	EG0005 affected94 at risk EG0011 affected84 at risk
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected94 at risk EG0015 affected84 at risk
BLOOD CHOLESTEROL INCREASED	Investigations	MedDRA	Systematic Assessment	EG0002 affected94 at risk EG0015 affected84 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0005 affected94 at risk EG0015 affected84 at risk
HEADACHE	Nervous system disorders	MedDRA	Systematic Assessment	EG0004 affected94 at risk EG0016 affected84 at risk
MULTIPLE SCLEROSIS RELAPSE	Nervous system disorders	MedDRA	Systematic Assessment	EG00022 affected94 at risk EG00115 affected84 at risk
DEPRESSION	Psychiatric disorders	MedDRA	Systematic Assessment	EG0004 affected94 at risk EG0018 affected84 at risk
SLEEP DISORDER	Psychiatric disorders	MedDRA	Systematic Assessment	EG00010 affected94 at risk EG0014 affected84 at risk
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0003 affected94 at risk EG0018 affected84 at risk
HYPERTENSION	Vascular disorders	MedDRA	Systematic Assessment	EG0004 affected94 at risk EG0019 affected84 at risk

ID	Term
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
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
D001519	Behavior

ID	Term
D009043	Motor Activity
D009068	Movement
D009142	Musculoskeletal Physiological Phenomena
D055687	Musculoskeletal and Neural Physiological Phenomena

ID	Term
D005221	Fatigue
D009103	Multiple Sclerosis
D009043	Motor Activity