Multiple Sclerosis
Conditions
Brief summary
This is a multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study followed by active treatment, to evaluate the efficacy, safety and tolerability of two doses of oral administration of laquinimod in participants with RRMS. The study has 2 periods: Period 1, the double-blind, placebo-controlled period (up to 24 months) and Period 2, the active treatment period (24 months).
Interventions
DRUGLaquinimod
Laquinimod will be administered as per the dose and schedule specified in the respective arms.
DRUGPlacebo
Placebo matching to laquinimod will be administered as per the schedule specified in the respective arms.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have a confirmed and documented multiple sclerosis (MS) diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course. * Participants must be ambulatory with Kurtzke's expanded disability status scale (EDSS) score of 0 to 5.5 in both screening and randomization visits. * Participants must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment \[intravenous (IV), intramuscular (IM) and/or per os (PO)/oral\] or adrenocorticotrophic hormone, 60 days prior to randomization. * Participants must have experienced at least one documented relapse in the 12 months prior to randomization. * Participants must have disease duration of not more than 15 years. * Women of child-bearing potential (for example, women who are not postmenopausal or surgically sterilized) must practice an acceptable method of birth control for 30 days before taking the study drug and two acceptable methods of birth control during the duration of the study and until 30 days after the last dose of study medication. * Additional criteria apply, please contact the investigator for more information.
Exclusion criteria
* Participants with progressive forms of MS. * Participants with neuromyelitis optica. * Use of experimental or investigational drugs and/or participation in drug clinical studies within the 6 months prior to randomization. * Use of immunosuppressive agents or cytotoxic agents, including cyclophosphamide, within 6 months prior to randomization. * Use of either of the following within 2 years prior to randomization visit: natalizumab (Tysabri®), rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab. * Use of teriflunomide (Aubagio®) within 2 years prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to randomization. * Previous treatment with glatiramer acetate (Copaxone®) Interferon β (either 1a or 1b), fingolimod (Gilenya®), dimethyl fumarate (Tecfidera®) or intravenous immunoglobulins within 2 months prior to randomization. * Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to randomization. * Previous use of mitoxantrone (Novantrone®), cladribine, or alemtuzumab (Lemtrada®). * Previous use of laquinimod. * Previous total body irradiation or total lymphoid irradiation. * Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation. * Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to randomization. * Use of inducers of CYP3A4 within 2 weeks prior to randomization visit. * Pregnancy or breastfeeding. * A known history of sensitivity to gadolinium (Gd). * Inability to successfully undergo magnetic resonance imaging (MRI) scanning. * Participants who underwent endovascular treatment for chronic cerebrospinal venous insufficiency within 3 months prior to randomization. * Additional criteria apply, please contact the investigator for more information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months) | Baseline to Month 24 | Time to CDP was defined as the time to a sustained increase in Kurtzke's Expanded Disability Status Scale (EDSS) score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least three months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]). Data is presented as distribution of CDP (number of participants with CDP) sustained for 3 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15 | Baseline, Month 15 | Brain atrophy was defined by the percent change in brain volume from baseline to Month 15. For participants who prematurely discontinued treatment or completed the placebo-controlled phase before Month 15, the last available measurement was used, provided it was performed at least 9 months following the initiation of study drug. |
| Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse) | Baseline to Month 24 | Relapse was defined as appearance of one or more new neurological abnormalities or reappearance or worsening of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in absence of fever or any infection) and immediately preceded by an improving neurological state of at least 30 days from onset of previous relapse. An event was counted as a relapse only when the participant's symptoms were accompanied by observed objective neurological changes, consistent with an increase of at least 0.5 in EDSS; or one grade in score of 2 or more of 7 Functional Systems (FS) (excluding changes in bowel or bladder function or cognition); or 2 grades in score of one of the FS as compared to previous evaluation. EDSS assesses disability in 8 FS with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of relapsing participants (number of participants with confirmed relapse). |
| Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months) | Baseline to Month 24 | Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 6 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 6 months. |
| Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months) | Baseline to Month 24 | Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 9 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 9 months. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase), endpoint (Month 24 of active-treatment phase) | ECG parameters included: PR interval, QRS interval, QTcF and QTcB. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. |
| Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry | Baseline up to Month 24 | Potentially clinically significant serum chemistry abnormalities included: Glucose \<=3 and \>=13.88 millimoles per liter (mmol/L); Alanine aminotransferase (ALT) (in units per liter \[U/L\]), aspartate aminotransferase (AST) (in U/L), alkaline phosphatase (in U/L), gamma-glutamyltransferase (GGT) (in U/L), creatine phosphokinase (CPK) (in U/L), C-reactive protein (CRP) (in milligrams per liter \[mg/L\]), pancreatic amylase (in U/L)\>=3 \* upper limit of normal (ULN); Fibrinogen \>=6 grams per liter (gm/L); Sodium \<=130 and \>=150 mmol/L; Potassium \<=3.2 and \>=5.5 mmol/L; Calcium \<=1.87 and \>=2.75 mmol/L; Phosphate \<=0.65 and \>=1.61 mmol/L. |
| Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs) | Baseline up to Month 24 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. |
| Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values | Baseline up to Month 24 | Potentially clinically significant hematological abnormalities included: Hemoglobin \<=11.5 grams per deciliter (gm/dL) in males and \<=10 gm/dL in females; White blood cells (WBCs) count \<=2.5 and \>=21\*10\^9 per liter (L); Absolute neutrophil count (ANC) \<=1.49\*10\^9 per L; Platelet count \<=100 and \>=600\*10\^9 per L. |
| Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values | Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase | Potentially clinically significant hematological abnormalities included: Hemoglobin \<=11.5, \>=20 gm/dL in males, and \<=10, \>=18.5 gm/dL in females; WBCs count \<=2.5 and \>=21\*10\^9 per L; ANC \<=1.49\*10\^9 per L; Platelet count \<=100 and \>=600\*10\^9 per L. |
| Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry | Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase | Potentially clinically significant serum chemistry abnormalities included: Glucose \<=3 and \>=13.88 mmol/L; ALT (in U/L), AST (in U/L), alkaline phosphatase (in U/L), GGT (in U/L), CPK (in U/L), CRP (in mg/L), pancreatic amylase (in U/L)\>=3 \* ULN; Fibrinogen \>=6 gm/L; Sodium \<=130 and \>=150 mmol/L; Potassium \<=3.2 and \>=5.5 mmol/L; Calcium \<=1.87 and \>=2.75 mmol/L; Phosphate \<=0.65 and \>=1.61 mmol/L; Blood urea nitrogen (in mmol/L); Total bilirubin \>=28 micromols per liter (micromols/L); Creatinine \>=117 micromols/L; Albumin \<=25 gm/L. |
| Active-Treatment Phase: Number of Participants With AEs | Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. |
| Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities | Baseline up to Week 24 | Clinically significant vital signs abnormalities included: Pulse rate: greater than or equal to (\>=) 120 beats per minute (bpm) and increase from baseline of \>=30 bpm, \<=45 bpm and decrease from baseline of \>=30 bpm; Systolic blood pressure: \>=180 millimeters of mercury (mmHg) and increase from baseline of \>=30 mmHg, \<=90 and decrease from baseline of \>=30 mmHg; Diastolic blood pressure: \>=100 mmHg and increase from baseline of \>=20 mmHg, \<=50 mmHg and decrease from baseline of \>=20 mmHg. |
| Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities | Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase | Clinically significant vital signs abnormalities included: Pulse rate: \>=120 bpm and increase from baseline of \>=30 bpm, \<=45 bpm and decrease from baseline of \>=30 bpm; Systolic blood pressure: \>=180 mmHg and increase from baseline of \>=30 mmHg, \<=90 and decrease from baseline of \>=30 mmHg; Diastolic blood pressure: \>=100 mmHg and increase from baseline of \>=20 mmHg, \<=50 mmHg and decrease from baseline of \>=20 mmHg. |
| Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Baseline, Endpoint (Month 24) | ECG parameters included: PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. |
Countries
Austria, Belarus, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Czechia, Estonia, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Latvia, Moldova, Montenegro, North Macedonia, Poland, Romania, Russia, Serbia, Slovakia, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
The study was conducted at 215 sites in 29 countries.
Participants by arm
| Arm | Count |
|---|---|
| Placebo-Controlled Phase: Placebo Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. | 740 |
| Placebo-Controlled Phase: Laquinimod 0.6 mg Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. | 727 |
| Placebo-Controlled Phase: Laquinimod 1.2 mg Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months. | 732 |
| Total | 2,199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Active Treatment Phase (24 Months) | Adverse Event | 0 | 0 | 0 | 4 | 1 | 0 |
| Active Treatment Phase (24 Months) | Death | 0 | 0 | 0 | 2 | 0 | 0 |
| Active Treatment Phase (24 Months) | Lack of Efficacy | 0 | 0 | 0 | 3 | 1 | 2 |
| Active Treatment Phase (24 Months) | Lost to Follow-up | 0 | 0 | 0 | 5 | 11 | 1 |
| Active Treatment Phase (24 Months) | Noncompliance | 0 | 0 | 0 | 0 | 4 | 2 |
| Active Treatment Phase (24 Months) | Other than specified | 0 | 0 | 0 | 1 | 5 | 2 |
| Active Treatment Phase (24 Months) | Participant withdrew per Sponsor request | 0 | 0 | 0 | 0 | 4 | 0 |
| Active Treatment Phase (24 Months) | Pregnancy | 0 | 0 | 0 | 2 | 5 | 2 |
| Active Treatment Phase (24 Months) | Study terminated by sponsor | 0 | 0 | 0 | 809 | 243 | 174 |
| Active Treatment Phase (24 Months) | Withdrawal by Subject | 0 | 0 | 0 | 58 | 220 | 32 |
| Placebo-Controlled Phase (24 Months) | Adverse Event | 8 | 13 | 9 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Death | 2 | 1 | 1 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Lack of Efficacy | 10 | 3 | 2 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Lost to Follow-up | 10 | 4 | 9 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Noncompliance with drug administration | 2 | 1 | 6 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Other than specified | 11 | 9 | 10 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Pregnancy | 12 | 5 | 9 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Placebo-Controlled Phase (24 Months) | Withdrawal by Subject | 88 | 68 | 154 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Laquinimod 1.2 mg |
|---|---|---|---|---|
| Age, Continuous | 36.3 years STANDARD_DEVIATION 9.14 | 35.9 years STANDARD_DEVIATION 8.95 | 36.8 years STANDARD_DEVIATION 9.25 | 36.1 years STANDARD_DEVIATION 9.22 |
| Age, Customized Adults (18-64 years) | 2199 Participants | 740 Participants | 727 Participants | 732 Participants |
| Kurtzke's Expanded Disability Status Scale (EDSS) Score Greater than (>) 4.0 | 265 Participants | 87 Participants | 90 Participants | 88 Participants |
| Kurtzke's Expanded Disability Status Scale (EDSS) Score Less than or equal to (<=) 4.0 | 1932 Participants | 653 Participants | 635 Participants | 644 Participants |
| Kurtzke's Expanded Disability Status Scale (EDSS) Score Missing | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Normalized Brain Volume | 1434.9 milliliters (mL) STANDARD_DEVIATION 93.07 | 1437.2 milliliters (mL) STANDARD_DEVIATION 93.37 | 1433.0 milliliters (mL) STANDARD_DEVIATION 92.49 | 1434.4 milliliters (mL) STANDARD_DEVIATION 93.41 |
| Race Asian | 8 Participants | 3 Participants | 2 Participants | 3 Participants |
| Race Black | 9 Participants | 3 Participants | 3 Participants | 3 Participants |
| Race Missing | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race Other | 27 Participants | 10 Participants | 8 Participants | 9 Participants |
| Race White | 2153 Participants | 724 Participants | 712 Participants | 717 Participants |
| Sex: Female, Male Female | 1473 Participants | 488 Participants | 510 Participants | 475 Participants |
| Sex: Female, Male Male | 726 Participants | 252 Participants | 217 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 727 | 1 / 732 | 2 / 740 | 2 / 580 | 0 / 268 | 0 / 215 | 0 / 311 | 0 / 236 |
| other Total, other adverse events | 262 / 727 | 286 / 732 | 243 / 740 | 102 / 580 | 46 / 268 | 35 / 215 | 43 / 311 | 43 / 236 |
| serious Total, serious adverse events | 57 / 727 | 49 / 732 | 43 / 740 | 24 / 580 | 10 / 268 | 5 / 215 | 5 / 311 | 9 / 236 |
Outcome results
Primary
Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months)
Time to CDP was defined as the time to a sustained increase in Kurtzke's Expanded Disability Status Scale (EDSS) score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least three months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]). Data is presented as distribution of CDP (number of participants with CDP) sustained for 3 months.
Time frame: Baseline to Month 24
Population: ITT analysis set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months) | 73 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months) | 66 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months) | 69 Participants |
Comparison: The primary analysis for the comparison between laquinimod 0.6 mg versus placebo was conducted using the baseline adjusted Cox proportional hazards model. Categorical EDSS at baseline (less than or equal to \[\<=\] 4 or greater than \[\>\] 4), country/geographical region (CGR), categorical age at baseline (\<=38 or \>38), and T2 volume at baseline were included as covariates in the model.p-value: =0.705795% CI: [0.668, 1.313]Cox proportional hazards model
Secondary
Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15
Brain atrophy was defined by the percent change in brain volume from baseline to Month 15. For participants who prematurely discontinued treatment or completed the placebo-controlled phase before Month 15, the last available measurement was used, provided it was performed at least 9 months following the initiation of study drug.
Time frame: Baseline, Month 15
Population: The modified intent-to-treat 1 (mITT1) analysis set included data from all randomized participants at the Month 15 visit. Here, 'Overall number of participants analyzed' = Participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15 | -0.8 percent change | Standard Deviation 1.02 |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15 | -0.4 percent change | Standard Deviation 1.01 |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15 | -0.4 percent change | Standard Deviation 1.05 |
Secondary
Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months)
Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 6 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 6 months.
Time frame: Baseline to Month 24
Population: ITT analysis set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months) | 49 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months) | 49 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months) | 51 Participants |
Secondary
Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months)
Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 9 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 9 months.
Time frame: Baseline to Month 24
Population: ITT analysis set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months) | 38 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months) | 38 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months) | 39 Participants |
Secondary
Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse)
Relapse was defined as appearance of one or more new neurological abnormalities or reappearance or worsening of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in absence of fever or any infection) and immediately preceded by an improving neurological state of at least 30 days from onset of previous relapse. An event was counted as a relapse only when the participant's symptoms were accompanied by observed objective neurological changes, consistent with an increase of at least 0.5 in EDSS; or one grade in score of 2 or more of 7 Functional Systems (FS) (excluding changes in bowel or bladder function or cognition); or 2 grades in score of one of the FS as compared to previous evaluation. EDSS assesses disability in 8 FS with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of relapsing participants (number of participants with confirmed relapse).
Time frame: Baseline to Month 24
Population: ITT analysis set included all randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse) | 332 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse) | 269 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse) | 222 Participants |
Other Pre-specified
Active-Treatment Phase: Number of Participants With AEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.
Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Population: Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Active-Treatment Phase: Number of Participants With AEs | 442 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active-Treatment Phase: Number of Participants With AEs | 241 Participants |
Other Pre-specified
Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities
Clinically significant vital signs abnormalities included: Pulse rate: \>=120 bpm and increase from baseline of \>=30 bpm, \<=45 bpm and decrease from baseline of \>=30 bpm; Systolic blood pressure: \>=180 mmHg and increase from baseline of \>=30 mmHg, \<=90 and decrease from baseline of \>=30 mmHg; Diastolic blood pressure: \>=100 mmHg and increase from baseline of \>=20 mmHg, \<=50 mmHg and decrease from baseline of \>=20 mmHg.
Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Population: Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities | 17 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities | 7 Participants |
Other Pre-specified
Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values
Potentially clinically significant hematological abnormalities included: Hemoglobin \<=11.5, \>=20 gm/dL in males, and \<=10, \>=18.5 gm/dL in females; WBCs count \<=2.5 and \>=21\*10\^9 per L; ANC \<=1.49\*10\^9 per L; Platelet count \<=100 and \>=600\*10\^9 per L.
Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Population: Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values | 886 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values | 499 Participants |
Other Pre-specified
Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry
Potentially clinically significant serum chemistry abnormalities included: Glucose \<=3 and \>=13.88 mmol/L; ALT (in U/L), AST (in U/L), alkaline phosphatase (in U/L), GGT (in U/L), CPK (in U/L), CRP (in mg/L), pancreatic amylase (in U/L)\>=3 \* ULN; Fibrinogen \>=6 gm/L; Sodium \<=130 and \>=150 mmol/L; Potassium \<=3.2 and \>=5.5 mmol/L; Calcium \<=1.87 and \>=2.75 mmol/L; Phosphate \<=0.65 and \>=1.61 mmol/L; Blood urea nitrogen (in mmol/L); Total bilirubin \>=28 micromols per liter (micromols/L); Creatinine \>=117 micromols/L; Albumin \<=25 gm/L.
Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Population: Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry | 887 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry | 501 Participants |
Other Pre-specified
Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters
ECG parameters included: PR interval, QRS interval, QTcF and QTcB. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.
Time frame: Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase), endpoint (Month 24 of active-treatment phase)
Population: Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase and had ECG shift from baseline data available.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Normal - Abnormal NCS | 137 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal NCS - Abnormal CS | 4 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal NCS - Normal | 18 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal CS - Normal | 0 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Normal - Abnormal CS | 7 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal NCS - Abnormal NCS | 81 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal CS - Abnormal CS | 0 Participants |
| Placebo-Controlled Phase: Placebo | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Normal - Normal | 641 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal CS - Abnormal CS | 1 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Normal - Normal | 353 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Normal - Abnormal NCS | 80 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Normal - Abnormal CS | 5 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal NCS - Normal | 17 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal NCS - Abnormal NCS | 45 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal NCS - Abnormal CS | 0 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal CS - Normal | 0 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
Other Pre-specified
Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.
Time frame: Baseline up to Month 24
Population: Safety analysis set included all participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs) | 546 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs) | 565 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs) | 575 Participants |
Other Pre-specified
Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities
Clinically significant vital signs abnormalities included: Pulse rate: greater than or equal to (\>=) 120 beats per minute (bpm) and increase from baseline of \>=30 bpm, \<=45 bpm and decrease from baseline of \>=30 bpm; Systolic blood pressure: \>=180 millimeters of mercury (mmHg) and increase from baseline of \>=30 mmHg, \<=90 and decrease from baseline of \>=30 mmHg; Diastolic blood pressure: \>=100 mmHg and increase from baseline of \>=20 mmHg, \<=50 mmHg and decrease from baseline of \>=20 mmHg.
Time frame: Baseline up to Week 24
Population: Safety analysis set included all participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities | 21 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities | 21 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities | 29 Participants |
Other Pre-specified
Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values
Potentially clinically significant hematological abnormalities included: Hemoglobin \<=11.5 grams per deciliter (gm/dL) in males and \<=10 gm/dL in females; White blood cells (WBCs) count \<=2.5 and \>=21\*10\^9 per liter (L); Absolute neutrophil count (ANC) \<=1.49\*10\^9 per L; Platelet count \<=100 and \>=600\*10\^9 per L.
Time frame: Baseline up to Month 24
Population: Safety analysis set included all participants who were randomized and received at least one dose of study drug. Here, 'Overall number of participants analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values | 71 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values | 78 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values | 83 Participants |
Other Pre-specified
Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry
Potentially clinically significant serum chemistry abnormalities included: Glucose \<=3 and \>=13.88 millimoles per liter (mmol/L); Alanine aminotransferase (ALT) (in units per liter \[U/L\]), aspartate aminotransferase (AST) (in U/L), alkaline phosphatase (in U/L), gamma-glutamyltransferase (GGT) (in U/L), creatine phosphokinase (CPK) (in U/L), C-reactive protein (CRP) (in milligrams per liter \[mg/L\]), pancreatic amylase (in U/L)\>=3 \* upper limit of normal (ULN); Fibrinogen \>=6 grams per liter (gm/L); Sodium \<=130 and \>=150 mmol/L; Potassium \<=3.2 and \>=5.5 mmol/L; Calcium \<=1.87 and \>=2.75 mmol/L; Phosphate \<=0.65 and \>=1.61 mmol/L.
Time frame: Baseline up to Month 24
Population: Safety analysis set included all participants who were randomized and received at least one dose of study drug. Here, 'Overall number of participants analyzed'=participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry | 157 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry | 165 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry | 187 Participants |
Other Pre-specified
Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
ECG parameters included: PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.
Time frame: Baseline, Endpoint (Month 24)
Population: Safety analysis set included all participants who were randomized and received at least one dose of study drug. Here, 'Overall number of participants analyzed=participants evaluable for this outcome measure.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Normal | 32 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal CS | 1 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal CS | 1 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal NCS | 98 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Normal | 463 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal CS | 0 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal NCS | 139 Participants |
| Placebo-Controlled Phase: Placebo | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Normal | 0 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal NCS | 96 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Normal | 467 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal NCS | 124 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal CS | 6 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Normal | 27 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal CS | 1 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Normal | 1 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| Placebo-Controlled Phase: Laquinimod 0.6 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal CS | 1 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal CS | 5 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Normal | 470 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Normal | 0 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal NCS | 126 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal CS | 3 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal NCS | 90 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Normal | 28 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| Placebo-Controlled Phase: Laquinimod 1.2 mg | Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal CS | 2 Participants |