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Trial record 1 of 1 for:    CBAF312A2304
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Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)

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ClinicalTrials.gov Identifier: NCT01665144
Recruitment Status : Active, not recruiting
First Posted : August 15, 2012
Results First Posted : October 31, 2018
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Secondary Progressive Multiple Sclerosis
Interventions Drug: BAF312
Drug: Placebo
Enrollment 1652
Recruitment Details  
Pre-assignment Details During the core, eligible patients were randomized in a 2:1 ratio to siponimod (BAF312) or placebo.
Arm/Group Title Siponimod (BAF312) Placebo
Hide Arm/Group Description Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration. Matching placebo to BAF312 was administered orally during the Core Part of the trial.
Period Title: Overall Study
Started 1105 546
Safety Set 1099 546
Full Analysis Set 1099 546
Completed 903 424
Not Completed 202 122
Reason Not Completed
New therapy for study indication             2             1
Technical problems             2             0
Death             3             1
Protocol deviation             3             1
Non-compliance w/study treatment             5             0
Progressive disease             8             4
Lost to Follow-up             9             8
Physician Decision             13             1
Lack of Efficacy             16             11
Adverse Event             45             18
Withdrawal by Subject             96             77
Arm/Group Title Siponimod (BAF312) Placebo Total
Hide Arm/Group Description Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration. Matching placebo to BAF312 was administered orally during the Core Part of the trial. Total of all reporting groups
Overall Number of Baseline Participants 1105 546 1651
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1105 participants 546 participants 1651 participants
48.0  (7.84) 48.1  (7.94) 48.0  (7.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1105 participants 546 participants 1651 participants
Female
669
  60.5%
323
  59.2%
992
  60.1%
Male
436
  39.5%
223
  40.8%
659
  39.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1105 participants 546 participants 1651 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
31
   2.8%
18
   3.3%
49
   3.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
7
   0.6%
3
   0.5%
10
   0.6%
White
1050
  95.0%
513
  94.0%
1563
  94.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
17
   1.5%
12
   2.2%
29
   1.8%
1.Primary Outcome
Title Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)
Hide Description The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.
Time Frame Baseline, every 3 month up to the maximum of approximately 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Full analysis set (FAS), which comprised all randomized patients with assigned treatments who took at least one dose of study medication, was considered for the analysis. Only participants from the FAS with non-missing covariates were analyzed for this outcome.
Arm/Group Title Siponimod (BAF312) Placebo
Hide Arm/Group Description:
Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration.
Matching placebo to BAF312 was administered orally during the Core Part of the trial.
Overall Number of Participants Analyzed 1096 545
Measure Type: Number
Unit of Measure: Percentage of participants
26.3 31.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Siponimod (BAF312), Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0134
Comments [Not Specified]
Method Cox proportional hazards model
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.65 to 0.95
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Efficacy of BAF312 Relative to Placebo in Confirmed Worsening of 25 Foot Walk Test
Hide Description Delay in time to 3 month confirmed worsening of at least 20% from baseline in the timed 25 foot walk test.
Time Frame Baseline , every 3 months up to the maximum of approximately 3 years
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Efficacy of BAF312 Relative to Placebo in Reducing the Increase in T2 Lesion Volume
Hide Description Efficacy is shown by the reduction of the increase in T1 lesion volume.
Time Frame Baseline, every year up to the maximum of approximately 3 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title The Delay in Time to Confirmed Disability Progression as Measured by EDSS.
Hide Description Confirmed disability is defined as increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.
Time Frame Baseline, every 6 months up to the maximum of approximately 3 years
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Efficacy of BAF Relative to Placebo in Annualized Relapses Rate and Time to the First Relapse
Hide Description Efficacy of BAF312 relative to placebo was measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses.
Time Frame Baseline every 3 months up to the maximum of approximately 3 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Overall Response Rate on the MSWS-12.
Hide Description The overall response of the effect of BAF312 compared to placebo patients on the patient reported outcome form MSWS-12.
Time Frame Baseline, every 6 months up to the maximum of approximately 3 years
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Effect on Inflammatory Disease Activity and Burden of Disease as Measured by MRI
Hide Description Effect of BAF312 relative to placebo on disease activity and burden of disease as measured by Gd-T1 lesion, new/enlarged T2 lesion, and brain atrophy on brain MRI scans.
Time Frame Baseline, every 12 month up to the maximum of approximately 3 years
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Effect on 3-month Confirmed Disability Progression as Defined by EDSS in Predefined Sub-groups
Hide Description effect on confirmed disability progression in pre-defined subgroups, including patients with or without superimposed relapses, rapidly evolving patients with 1.5 point or greater change in EDSS score in 2 years prior to enrollment into the study. Patients with score of 4 or more in MSSS and those who don't meet this criteria.
Time Frame Baseline, every 3 months up to the maximum of approximately 3 years
Outcome Measure Data Not Reported
Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3.5 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Siponimod (BAF312) Placebo
Hide Arm/Group Description Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on 2 mg BAF312 daily for a variable duration. Matching placebo to BAF312 was administered orally during the Core Part of the trial.
All-Cause Mortality
Siponimod (BAF312) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   4/1099 (0.36%)   4/546 (0.73%) 
Show Serious Adverse Events Hide Serious Adverse Events
Siponimod (BAF312) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   197/1099 (17.93%)   83/546 (15.20%) 
Blood and lymphatic system disorders     
ANAEMIA  1  0/1099 (0.00%)  2/546 (0.37%) 
LEUKOPENIA  1  1/1099 (0.09%)  0/546 (0.00%) 
THROMBOCYTOPENIA  1  1/1099 (0.09%)  0/546 (0.00%) 
Cardiac disorders     
ACUTE CORONARY SYNDROME  1  1/1099 (0.09%)  0/546 (0.00%) 
ACUTE MYOCARDIAL INFARCTION  1  1/1099 (0.09%)  1/546 (0.18%) 
ANGINA PECTORIS  1  1/1099 (0.09%)  1/546 (0.18%) 
ATRIAL FIBRILLATION  1  1/1099 (0.09%)  0/546 (0.00%) 
ATRIOVENTRICULAR BLOCK SECOND DEGREE  1  2/1099 (0.18%)  0/546 (0.00%) 
BRADYCARDIA  1  3/1099 (0.27%)  0/546 (0.00%) 
BUNDLE BRANCH BLOCK LEFT  1  1/1099 (0.09%)  0/546 (0.00%) 
CORONARY ARTERY DISEASE  1  1/1099 (0.09%)  1/546 (0.18%) 
MYOCARDIAL ISCHAEMIA  1  1/1099 (0.09%)  0/546 (0.00%) 
PALPITATIONS  1  1/1099 (0.09%)  0/546 (0.00%) 
SINUS TACHYCARDIA  1  1/1099 (0.09%)  0/546 (0.00%) 
SUPRAVENTRICULAR TACHYCARDIA  1  0/1099 (0.00%)  1/546 (0.18%) 
Ear and labyrinth disorders     
VERTIGO  1  0/1099 (0.00%)  1/546 (0.18%) 
Eye disorders     
BLINDNESS  1  1/1099 (0.09%)  0/546 (0.00%) 
CATARACT  1  0/1099 (0.00%)  1/546 (0.18%) 
DIPLOPIA  1  0/1099 (0.00%)  1/546 (0.18%) 
MACULAR OEDEMA  1  3/1099 (0.27%)  0/546 (0.00%) 
RETINAL DETACHMENT  1  0/1099 (0.00%)  1/546 (0.18%) 
RETINOSCHISIS  1  0/1099 (0.00%)  1/546 (0.18%) 
Gastrointestinal disorders     
ABDOMINAL PAIN UPPER  1  0/1099 (0.00%)  1/546 (0.18%) 
ANAL FISSURE  1  0/1099 (0.00%)  1/546 (0.18%) 
CONSTIPATION  1  2/1099 (0.18%)  1/546 (0.18%) 
DIARRHOEA  1  1/1099 (0.09%)  1/546 (0.18%) 
DUODENAL ULCER  1  0/1099 (0.00%)  1/546 (0.18%) 
GASTRIC ULCER PERFORATION  1  0/1099 (0.00%)  1/546 (0.18%) 
GASTRITIS EROSIVE  1  1/1099 (0.09%)  0/546 (0.00%) 
INCARCERATED INGUINAL HERNIA  1  1/1099 (0.09%)  0/546 (0.00%) 
INGUINAL HERNIA  1  1/1099 (0.09%)  0/546 (0.00%) 
INTESTINAL OBSTRUCTION  1  1/1099 (0.09%)  1/546 (0.18%) 
NAUSEA  1  1/1099 (0.09%)  0/546 (0.00%) 
OESOPHAGITIS  1  0/1099 (0.00%)  1/546 (0.18%) 
PANCREATITIS ACUTE  1  0/1099 (0.00%)  1/546 (0.18%) 
SMALL INTESTINAL OBSTRUCTION  1  0/1099 (0.00%)  1/546 (0.18%) 
UMBILICAL HERNIA, OBSTRUCTIVE  1  1/1099 (0.09%)  0/546 (0.00%) 
VOMITING  1  1/1099 (0.09%)  0/546 (0.00%) 
General disorders     
ASTHENIA  1  2/1099 (0.18%)  0/546 (0.00%) 
FATIGUE  1  1/1099 (0.09%)  0/546 (0.00%) 
GAIT DISTURBANCE  1  1/1099 (0.09%)  3/546 (0.55%) 
OEDEMA PERIPHERAL  1  0/1099 (0.00%)  1/546 (0.18%) 
PYREXIA  1  2/1099 (0.18%)  0/546 (0.00%) 
Hepatobiliary disorders     
BILIARY COLIC  1  1/1099 (0.09%)  0/546 (0.00%) 
CHOLECYSTITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
CHOLECYSTITIS ACUTE  1  1/1099 (0.09%)  0/546 (0.00%) 
CHOLELITHIASIS  1  1/1099 (0.09%)  0/546 (0.00%) 
HEPATOTOXICITY  1  1/1099 (0.09%)  0/546 (0.00%) 
NON-ALCOHOLIC STEATOHEPATITIS  1  0/1099 (0.00%)  1/546 (0.18%) 
Immune system disorders     
HYPERSENSITIVITY  1  1/1099 (0.09%)  0/546 (0.00%) 
Infections and infestations     
APPENDICEAL ABSCESS  1  1/1099 (0.09%)  0/546 (0.00%) 
APPENDICITIS  1  3/1099 (0.27%)  0/546 (0.00%) 
BACTERAEMIA  1  1/1099 (0.09%)  0/546 (0.00%) 
CAMPYLOBACTER GASTROENTERITIS  1  0/1099 (0.00%)  1/546 (0.18%) 
CELLULITIS  1  2/1099 (0.18%)  0/546 (0.00%) 
CHORIORETINITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
DIVERTICULITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
ESCHERICHIA URINARY TRACT INFECTION  1  1/1099 (0.09%)  0/546 (0.00%) 
GASTROENTERITIS  1  2/1099 (0.18%)  1/546 (0.18%) 
GASTROENTERITIS PROTEUS  1  0/1099 (0.00%)  1/546 (0.18%) 
HEPATITIS E  1  1/1099 (0.09%)  0/546 (0.00%) 
HERPES ZOSTER  1  1/1099 (0.09%)  0/546 (0.00%) 
HERPES ZOSTER MENINGITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
INFLUENZA  1  1/1099 (0.09%)  1/546 (0.18%) 
LABYRINTHITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
NASAL ABSCESS  1  1/1099 (0.09%)  0/546 (0.00%) 
ORAL VIRAL INFECTION  1  1/1099 (0.09%)  0/546 (0.00%) 
PNEUMONIA  1  1/1099 (0.09%)  2/546 (0.37%) 
POSTOPERATIVE WOUND INFECTION  1  1/1099 (0.09%)  1/546 (0.18%) 
PYELONEPHRITIS  1  0/1099 (0.00%)  1/546 (0.18%) 
PYELONEPHRITIS CHRONIC  1  1/1099 (0.09%)  0/546 (0.00%) 
SEPSIS  1  1/1099 (0.09%)  0/546 (0.00%) 
SEPTIC SHOCK  1  2/1099 (0.18%)  0/546 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION  1  3/1099 (0.27%)  0/546 (0.00%) 
URINARY TRACT INFECTION  1  15/1099 (1.36%)  7/546 (1.28%) 
UROSEPSIS  1  5/1099 (0.45%)  1/546 (0.18%) 
WOUND INFECTION  1  0/1099 (0.00%)  1/546 (0.18%) 
Injury, poisoning and procedural complications     
ANKLE FRACTURE  1  2/1099 (0.18%)  0/546 (0.00%) 
CERVICAL VERTEBRAL FRACTURE  1  1/1099 (0.09%)  0/546 (0.00%) 
CLAVICLE FRACTURE  1  2/1099 (0.18%)  0/546 (0.00%) 
CONCUSSION  1  5/1099 (0.45%)  0/546 (0.00%) 
CONTUSION  1  1/1099 (0.09%)  0/546 (0.00%) 
EYE CONTUSION  1  1/1099 (0.09%)  0/546 (0.00%) 
FALL  1  2/1099 (0.18%)  0/546 (0.00%) 
FEMORAL NECK FRACTURE  1  3/1099 (0.27%)  1/546 (0.18%) 
FRACTURE DISPLACEMENT  1  1/1099 (0.09%)  0/546 (0.00%) 
HEAD INJURY  1  0/1099 (0.00%)  1/546 (0.18%) 
HIP FRACTURE  1  0/1099 (0.00%)  2/546 (0.37%) 
INJURY CORNEAL  1  1/1099 (0.09%)  0/546 (0.00%) 
LACERATION  1  4/1099 (0.36%)  0/546 (0.00%) 
LOWER LIMB FRACTURE  1  0/1099 (0.00%)  1/546 (0.18%) 
MENISCUS INJURY  1  0/1099 (0.00%)  1/546 (0.18%) 
RADIUS FRACTURE  1  1/1099 (0.09%)  0/546 (0.00%) 
RIB FRACTURE  1  1/1099 (0.09%)  0/546 (0.00%) 
SPINAL COMPRESSION FRACTURE  1  1/1099 (0.09%)  0/546 (0.00%) 
SPLENIC RUPTURE  1  1/1099 (0.09%)  0/546 (0.00%) 
SUBDURAL HAEMATOMA  1  1/1099 (0.09%)  0/546 (0.00%) 
TENDON RUPTURE  1  0/1099 (0.00%)  1/546 (0.18%) 
THERMAL BURN  1  1/1099 (0.09%)  0/546 (0.00%) 
TIBIA FRACTURE  1  0/1099 (0.00%)  1/546 (0.18%) 
TRAUMATIC FRACTURE  1  1/1099 (0.09%)  0/546 (0.00%) 
TRAUMATIC HAEMORRHAGE  1  1/1099 (0.09%)  0/546 (0.00%) 
TRAUMATIC HAEMOTHORAX  1  1/1099 (0.09%)  0/546 (0.00%) 
TRAUMATIC LIVER INJURY  1  1/1099 (0.09%)  0/546 (0.00%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  10/1099 (0.91%)  2/546 (0.37%) 
ASPARTATE AMINOTRANSFERASE INCREASED  1  5/1099 (0.45%)  1/546 (0.18%) 
BLOOD BILIRUBIN INCREASED  1  2/1099 (0.18%)  0/546 (0.00%) 
BLOOD GLUCOSE INCREASED  1  1/1099 (0.09%)  0/546 (0.00%) 
CARBON MONOXIDE DIFFUSING CAPACITY DECREASED  1  1/1099 (0.09%)  0/546 (0.00%) 
COLUMBIA SUICIDE SEVERITY RATING SCALE ABNORMAL  1  2/1099 (0.18%)  0/546 (0.00%) 
HEART RATE DECREASED  1  1/1099 (0.09%)  0/546 (0.00%) 
HEPATIC ENZYME ABNORMAL  1  1/1099 (0.09%)  0/546 (0.00%) 
HEPATIC ENZYME INCREASED  1  1/1099 (0.09%)  0/546 (0.00%) 
LIVER FUNCTION TEST ABNORMAL  1  0/1099 (0.00%)  1/546 (0.18%) 
PULMONARY FUNCTION TEST DECREASED  1  1/1099 (0.09%)  0/546 (0.00%) 
WALKING DISTANCE TEST ABNORMAL  1  1/1099 (0.09%)  0/546 (0.00%) 
WEIGHT DECREASED  1  1/1099 (0.09%)  0/546 (0.00%) 
Metabolism and nutrition disorders     
DEHYDRATION  1  2/1099 (0.18%)  0/546 (0.00%) 
HAEMOCHROMATOSIS  1  1/1099 (0.09%)  0/546 (0.00%) 
SHOCK HYPOGLYCAEMIC  1  0/1099 (0.00%)  1/546 (0.18%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  1/1099 (0.09%)  0/546 (0.00%) 
ARTHRITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
BACK PAIN  1  1/1099 (0.09%)  0/546 (0.00%) 
BURSITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
FOOT DEFORMITY  1  1/1099 (0.09%)  0/546 (0.00%) 
INTERVERTEBRAL DISC PROTRUSION  1  1/1099 (0.09%)  1/546 (0.18%) 
LUMBAR SPINAL STENOSIS  1  1/1099 (0.09%)  0/546 (0.00%) 
MUSCULAR WEAKNESS  1  3/1099 (0.27%)  0/546 (0.00%) 
MUSCULOSKELETAL PAIN  1  1/1099 (0.09%)  0/546 (0.00%) 
MUSCULOSKELETAL STIFFNESS  1  0/1099 (0.00%)  1/546 (0.18%) 
OSTEOARTHRITIS  1  1/1099 (0.09%)  0/546 (0.00%) 
PATELLOFEMORAL PAIN SYNDROME  1  0/1099 (0.00%)  1/546 (0.18%) 
SPINAL DEFORMITY  1  1/1099 (0.09%)  0/546 (0.00%) 
SYNOVIAL CYST  1  1/1099 (0.09%)  0/546 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
BASAL CELL CARCINOMA  1  11/1099 (1.00%)  7/546 (1.28%) 
BENIGN NEOPLASM OF THYROID GLAND  1  1/1099 (0.09%)  0/546 (0.00%) 
BLADDER CANCER  1  0/1099 (0.00%)  1/546 (0.18%) 
BOWEN'S DISEASE  1  1/1099 (0.09%)  1/546 (0.18%) 
BREAST CANCER  1  1/1099 (0.09%)  1/546 (0.18%) 
CENTRAL NERVOUS SYSTEM LYMPHOMA  1  0/1099 (0.00%)  1/546 (0.18%) 
COLON CANCER STAGE IV  1  1/1099 (0.09%)  0/546 (0.00%) 
ENDOMETRIAL CANCER  1  1/1099 (0.09%)  0/546 (0.00%) 
GASTRIC CANCER  1  0/1099 (0.00%)  1/546 (0.18%) 
GASTROINTESTINAL MELANOMA  1  1/1099 (0.09%)  0/546 (0.00%) 
GLIOMA  1  0/1099 (0.00%)  1/546 (0.18%) 
LIP SQUAMOUS CELL CARCINOMA  1  1/1099 (0.09%)  0/546 (0.00%) 
LUNG ADENOCARCINOMA  1  0/1099 (0.00%)  1/546 (0.18%) 
LUNG ADENOCARCINOMA METASTATIC  1  1/1099 (0.09%)  0/546 (0.00%) 
MALIGNANT MELANOMA IN SITU  1  2/1099 (0.18%)  0/546 (0.00%) 
MELANOCYTIC NAEVUS  1  1/1099 (0.09%)  0/546 (0.00%) 
NEUROFIBROMA  1  1/1099 (0.09%)  0/546 (0.00%) 
PROSTATE CANCER  1  0/1099 (0.00%)  2/546 (0.37%) 
RENAL ONCOCYTOMA  1  0/1099 (0.00%)  1/546 (0.18%) 
SEMINOMA  1  2/1099 (0.18%)  0/546 (0.00%) 
SQUAMOUS CELL CARCINOMA  1  1/1099 (0.09%)  0/546 (0.00%) 
UTERINE LEIOMYOMA  1  1/1099 (0.09%)  1/546 (0.18%) 
Nervous system disorders     
ALLODYNIA  1  0/1099 (0.00%)  1/546 (0.18%) 
AMNESTIC DISORDER  1  0/1099 (0.00%)  1/546 (0.18%) 
APHASIA  1  1/1099 (0.09%)  0/546 (0.00%) 
ATAXIA  1  1/1099 (0.09%)  0/546 (0.00%) 
BRAIN INJURY  1  1/1099 (0.09%)  0/546 (0.00%) 
BRAIN STEM INFARCTION  1  1/1099 (0.09%)  0/546 (0.00%) 
CEREBROVASCULAR ACCIDENT  1  2/1099 (0.18%)  1/546 (0.18%) 
DISTURBANCE IN ATTENTION  1  1/1099 (0.09%)  0/546 (0.00%) 
DIZZINESS  1  1/1099 (0.09%)  0/546 (0.00%) 
DYSAESTHESIA  1  0/1099 (0.00%)  1/546 (0.18%) 
EPILEPSY  1  5/1099 (0.45%)  0/546 (0.00%) 
GENERALISED TONIC-CLONIC SEIZURE  1  1/1099 (0.09%)  0/546 (0.00%) 
HAEMORRHAGIC STROKE  1  0/1099 (0.00%)  1/546 (0.18%) 
HEAD TITUBATION  1  1/1099 (0.09%)  0/546 (0.00%) 
HEMIPARESIS  1  3/1099 (0.27%)  0/546 (0.00%) 
HYPOAESTHESIA  1  0/1099 (0.00%)  1/546 (0.18%) 
INTENTION TREMOR  1  1/1099 (0.09%)  0/546 (0.00%) 
INTRACRANIAL ANEURYSM  1  1/1099 (0.09%)  0/546 (0.00%) 
ISCHAEMIC STROKE  1  1/1099 (0.09%)  0/546 (0.00%) 
MERALGIA PARAESTHETICA  1  0/1099 (0.00%)  1/546 (0.18%) 
MULTIPLE SCLEROSIS  1  2/1099 (0.18%)  0/546 (0.00%) 
MULTIPLE SCLEROSIS RELAPSE  1  2/1099 (0.18%)  7/546 (1.28%) 
MUSCLE SPASTICITY  1  2/1099 (0.18%)  1/546 (0.18%) 
PARAPARESIS  1  0/1099 (0.00%)  3/546 (0.55%) 
PARTIAL SEIZURES  1  2/1099 (0.18%)  0/546 (0.00%) 
POLYNEUROPATHY  1  1/1099 (0.09%)  0/546 (0.00%) 
PUTAMEN HAEMORRHAGE  1  0/1099 (0.00%)  1/546 (0.18%) 
RADICULOPATHY  1  1/1099 (0.09%)  0/546 (0.00%) 
SEIZURE  1  4/1099 (0.36%)  0/546 (0.00%) 
STATUS MIGRAINOSUS  1  1/1099 (0.09%)  0/546 (0.00%) 
SUBARACHNOID HAEMATOMA  1  1/1099 (0.09%)  0/546 (0.00%) 
SYNCOPE  1  4/1099 (0.36%)  1/546 (0.18%) 
TRANSIENT ISCHAEMIC ATTACK  1  1/1099 (0.09%)  1/546 (0.18%) 
TREMOR  1  0/1099 (0.00%)  1/546 (0.18%) 
TRIGEMINAL NEURALGIA  1  3/1099 (0.27%)  0/546 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
ABORTION SPONTANEOUS  1  1/1099 (0.09%)  0/546 (0.00%) 
Psychiatric disorders     
ANXIETY  1  1/1099 (0.09%)  0/546 (0.00%) 
ANXIETY DISORDER DUE TO A GENERAL MEDICAL CONDITION  1  1/1099 (0.09%)  0/546 (0.00%) 
COMPLETED SUICIDE  1  1/1099 (0.09%)  0/546 (0.00%) 
DEPRESSED MOOD  1  1/1099 (0.09%)  0/546 (0.00%) 
DEPRESSION  1  5/1099 (0.45%)  2/546 (0.37%) 
DEPRESSION SUICIDAL  1  1/1099 (0.09%)  0/546 (0.00%) 
DEPRESSIVE SYMPTOM  1  1/1099 (0.09%)  0/546 (0.00%) 
EUPHORIC MOOD  1  1/1099 (0.09%)  0/546 (0.00%) 
HALLUCINATION  1  1/1099 (0.09%)  0/546 (0.00%) 
MANIA  1  1/1099 (0.09%)  0/546 (0.00%) 
MENTAL STATUS CHANGES  1  1/1099 (0.09%)  0/546 (0.00%) 
PANIC ATTACK  1  1/1099 (0.09%)  1/546 (0.18%) 
PSYCHOTIC DISORDER  1  1/1099 (0.09%)  0/546 (0.00%) 
SUICIDAL BEHAVIOUR  1  3/1099 (0.27%)  0/546 (0.00%) 
SUICIDAL IDEATION  1  3/1099 (0.27%)  1/546 (0.18%) 
SUICIDE ATTEMPT  1  4/1099 (0.36%)  3/546 (0.55%) 
Renal and urinary disorders     
ACUTE KIDNEY INJURY  1  1/1099 (0.09%)  0/546 (0.00%) 
BLADDER DYSFUNCTION  1  2/1099 (0.18%)  0/546 (0.00%) 
CALCULUS BLADDER  1  1/1099 (0.09%)  0/546 (0.00%) 
HYDRONEPHROSIS  1  2/1099 (0.18%)  1/546 (0.18%) 
NEPHROLITHIASIS  1  1/1099 (0.09%)  1/546 (0.18%) 
NEUROGENIC BLADDER  1  1/1099 (0.09%)  0/546 (0.00%) 
SINGLE FUNCTIONAL KIDNEY  1  1/1099 (0.09%)  0/546 (0.00%) 
URETEROLITHIASIS  1  1/1099 (0.09%)  0/546 (0.00%) 
URETHRAL STENOSIS  1  1/1099 (0.09%)  0/546 (0.00%) 
URGE INCONTINENCE  1  1/1099 (0.09%)  0/546 (0.00%) 
URINARY INCONTINENCE  1  2/1099 (0.18%)  0/546 (0.00%) 
URINARY RETENTION  1  3/1099 (0.27%)  2/546 (0.37%) 
Reproductive system and breast disorders     
CERVICAL DYSPLASIA  1  0/1099 (0.00%)  1/546 (0.18%) 
MENORRHAGIA  1  2/1099 (0.18%)  0/546 (0.00%) 
METRORRHAGIA  1  2/1099 (0.18%)  1/546 (0.18%) 
OVARIAN DISORDER  1  1/1099 (0.09%)  0/546 (0.00%) 
TESTICULAR ATROPHY  1  0/1099 (0.00%)  1/546 (0.18%) 
Respiratory, thoracic and mediastinal disorders     
PNEUMONIA ASPIRATION  1  1/1099 (0.09%)  0/546 (0.00%) 
PULMONARY EMBOLISM  1  1/1099 (0.09%)  1/546 (0.18%) 
PULMONARY HYPERTENSION  1  1/1099 (0.09%)  0/546 (0.00%) 
RESPIRATORY DEPRESSION  1  1/1099 (0.09%)  0/546 (0.00%) 
RESPIRATORY DISORDER  1  1/1099 (0.09%)  0/546 (0.00%) 
Skin and subcutaneous tissue disorders     
ACTINIC KERATOSIS  1  0/1099 (0.00%)  1/546 (0.18%) 
DECUBITUS ULCER  1  1/1099 (0.09%)  1/546 (0.18%) 
RASH  1  1/1099 (0.09%)  0/546 (0.00%) 
RASH PAPULAR  1  1/1099 (0.09%)  0/546 (0.00%) 
Social circumstances     
IMMOBILE  1  1/1099 (0.09%)  0/546 (0.00%) 
WALKING DISABILITY  1  0/1099 (0.00%)  1/546 (0.18%) 
Vascular disorders     
CIRCULATORY COLLAPSE  1  0/1099 (0.00%)  1/546 (0.18%) 
DEEP VEIN THROMBOSIS  1  1/1099 (0.09%)  0/546 (0.00%) 
HAEMATOMA  1  1/1099 (0.09%)  0/546 (0.00%) 
HYPERTENSION  1  1/1099 (0.09%)  0/546 (0.00%) 
ORTHOSTATIC HYPOTENSION  1  1/1099 (0.09%)  0/546 (0.00%) 
VENOUS THROMBOSIS LIMB  1  1/1099 (0.09%)  0/546 (0.00%) 
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Siponimod (BAF312) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   698/1099 (63.51%)   311/546 (56.96%) 
Gastrointestinal disorders     
DIARRHOEA  1  69/1099 (6.28%)  22/546 (4.03%) 
NAUSEA  1  73/1099 (6.64%)  19/546 (3.48%) 
General disorders     
FATIGUE  1  100/1099 (9.10%)  51/546 (9.34%) 
Infections and infestations     
INFLUENZA  1  72/1099 (6.55%)  40/546 (7.33%) 
NASOPHARYNGITIS  1  149/1099 (13.56%)  79/546 (14.47%) 
UPPER RESPIRATORY TRACT INFECTION  1  89/1099 (8.10%)  41/546 (7.51%) 
URINARY TRACT INFECTION  1  128/1099 (11.65%)  75/546 (13.74%) 
Injury, poisoning and procedural complications     
FALL  1  126/1099 (11.46%)  59/546 (10.81%) 
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  58/1099 (5.28%)  8/546 (1.47%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  49/1099 (4.46%)  35/546 (6.41%) 
BACK PAIN  1  66/1099 (6.01%)  43/546 (7.88%) 
PAIN IN EXTREMITY  1  60/1099 (5.46%)  21/546 (3.85%) 
Nervous system disorders     
DIZZINESS  1  74/1099 (6.73%)  26/546 (4.76%) 
HEADACHE  1  159/1099 (14.47%)  71/546 (13.00%) 
Psychiatric disorders     
DEPRESSION  1  44/1099 (4.00%)  28/546 (5.13%) 
Vascular disorders     
HYPERTENSION  1  114/1099 (10.37%)  41/546 (7.51%) 
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01665144     History of Changes
Other Study ID Numbers: CBAF312A2304
First Submitted: August 3, 2012
First Posted: August 15, 2012
Results First Submitted: August 6, 2018
Results First Posted: October 31, 2018
Last Update Posted: September 9, 2019