Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase 2 Clinical Study in Subjects With Primary Progressive Multiple Sclerosis to Assess the Efficacy, Safety and Tolerability of Two Oral Doses of Laquinimod Either of 0.6 mg/Day or 1.5mg/Day (Experimental Drug) as Compared to Placebo (ARPEGGIO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02284568
Recruitment Status : Completed
First Posted : November 6, 2014
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Primary Progressive Multiple Sclerosis
Interventions Drug: Placebo
Drug: Laquinimod
Enrollment 374
Recruitment Details  
Pre-assignment Details A total of 447 patients were screened for enrollment into this study. Of the patients screened, 374 patients met entry criteria and were enrolled into the study. One participant withdrew before taking any study drug.
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description 3 capsules containing placebo were administered orally once daily for at least 48 weeks. 1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks. 3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Period Title: Overall Study
Started 140 [1] 139 [1] 95 [1]
Safety Population 140 138 95
Completed Week 48 MRI - on Treatment 113 107 0
Completed 109 93 0
Not Completed 31 46 95
Reason Not Completed
Adverse Event             2             9             4
Withdrawal by Subject             22             21             1
Noncompliance with study drug admin             1             2             0
Noncompliance             1             0             0
Protocol Violation             0             1             0
Sponsor requested patient stop treatment             0             0             90
Lost to Follow-up             0             3             0
Lack of Efficacy             4             7             0
Other             1             2             0
Withdrew before taking study drug             0             1             0
[1]
Intent to treat (ITT) population
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg Total
Hide Arm/Group Description 3 capsules containing placebo were administered orally once daily for at least 48 weeks. 1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks. 3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe. Total of all reporting groups
Overall Number of Baseline Participants 140 139 95 374
Hide Baseline Analysis Population Description
Intent to treat population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 140 participants 139 participants 95 participants 374 participants
46.6  (7.18) 46.1  (6.68) 46.1  (7.21) 46.3  (6.99)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 139 participants 95 participants 374 participants
Female
67
  47.9%
57
  41.0%
45
  47.4%
169
  45.2%
Male
73
  52.1%
82
  59.0%
50
  52.6%
205
  54.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 139 participants 95 participants 374 participants
White
138
  98.6%
132
  95.0%
92
  96.8%
362
  96.8%
Black
0
   0.0%
2
   1.4%
2
   2.1%
4
   1.1%
Asian
0
   0.0%
2
   1.4%
0
   0.0%
2
   0.5%
Other
2
   1.4%
3
   2.2%
1
   1.1%
6
   1.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 139 participants 95 participants 374 participants
Not HIspanic or Latino
135
  96.4%
134
  96.4%
91
  95.8%
360
  96.3%
Hispanic or Latino
4
   2.9%
5
   3.6%
1
   1.1%
10
   2.7%
Unknown
1
   0.7%
0
   0.0%
3
   3.2%
4
   1.1%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 140 participants 139 participants 95 participants 374 participants
73.97  (16.809) 75.91  (16.668) 73.47  (14.831) 74.57  (16.275)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 140 participants 139 participants 95 participants 374 participants
171.25  (9.818) 172.61  (9.246) 171.03  (9.677) 171.70  (9.573)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 140 participants 139 participants 95 participants 374 participants
25.136  (5.0283) 25.373  (4.5539) 25.026  (4.1002) 25.196  (4.6208)
Time Since First MS Symptom   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 140 participants 139 participants 95 participants 374 participants
7.4  (5.22) 8.3  (6.33) 8.5  (5.61) 8.0  (5.76)
[1]
Measure Description: Multiple sclerosis (MS)
Time Since First PPMS Diagnosis   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 140 participants 139 participants 95 participants 374 participants
3.1  (2.98) 4.0  (4.05) 4.1  (4.04) 3.7  (3.70)
[1]
Measure Description: Primary progressive multiple sclerosis (PPMS)
Normalized Brain Volume   [1] 
Mean (Standard Deviation)
Unit of measure:  mL
Number Analyzed 140 participants 139 participants 95 participants 374 participants
1457.9  (109.78) 1461.3  (96.63) 1455.2  (101.44) 1458.5  (102.69)
[1]
Measure Description: Obtained from magnetic resonance imaging (MRI) scans
Expanded Disability Status Scale (EDSS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 140 participants 139 participants 95 participants 374 participants
EDSS score 3
10
   7.1%
12
   8.6%
10
  10.5%
32
   8.6%
EDSS score 3.5
27
  19.3%
25
  18.0%
20
  21.1%
72
  19.3%
EDSS score 4
24
  17.1%
30
  21.6%
18
  18.9%
72
  19.3%
EDSS score 4.5
26
  18.6%
19
  13.7%
17
  17.9%
62
  16.6%
EDSS score 5
17
  12.1%
15
  10.8%
6
   6.3%
38
  10.2%
EDSS score 5.5
24
  17.1%
23
  16.5%
16
  16.8%
63
  16.8%
EDSS score 6
9
   6.4%
12
   8.6%
4
   4.2%
25
   6.7%
EDSS score 6.5
3
   2.1%
3
   2.2%
4
   4.2%
10
   2.7%
[1]
Measure Description: EDSS is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS scale ranges from 0 to 10 in 0.5 unit increments with 0=no disability and 10=death due to MS. Only an Examining Neurologist administered the EDSS. The Examining Neurologist did not have access to the patient's medical records or source documents, including previous EDSS forms or adverse events.
1.Primary Outcome
Title Percent Brain Volume Change (PBVC) From Baseline to Week 48 Using a Repeated Measures ANCOVA Model
Hide Description Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. BA was analyzed using baseline-adjusted repeated measures analysis of covariance (ANCOVA- SAS® PROC MIXED) in which 1 contrast was constructed in order to compare between laquinimod 0.6 mg and placebo. The statistical model was a repeated measures analysis of covariance with treatment group, week, treatment group by week interaction, normalized brain volume at baseline, natural logarithm of T2 lesion volume at baseline, and country as fixed effects. Only on-treatment observations (include all the assessments done up to one month after the last dose of the study drug) were included. Values are adjusted means. The cancelled laquinimod 1.5 mg treatment arm was not included in the repeated measures ANCOVA model analysis. However PBVC by visit data are offered in outcome #2.
Time Frame Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48 and including early termination visits
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent to Treat 1 (mITT1) population with at least 1 post-baseline PBVC value and will include assessments taken up to/including early termination/study completion visit.
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description:
3 capsules containing placebo were administered orally once daily for at least 48 weeks.
1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.
3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Overall Number of Participants Analyzed 128 124 0
Mean (Standard Error)
Unit of Measure: percentage change from baseline
-0.454  (0.0897) -0.438  (0.0945)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Laquinimod 0.6 mg
Comments The statistical model was a repeated measures analysis of covariance with treatment group, week, treatment group by week interaction, normalized brain volume at baseline, natural logarithm of T2 lesion volume at baseline, and country as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.903
Comments significance at 0.05.
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.016
Confidence Interval (2-Sided) 95%
-0.2390 to 0.2705
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.1293
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percent Brain Volume Change (PBVC) From Baseline to Weeks 24 and 48
Hide Description Brain atrophy (BA) was measured using magnetic resonance imaging (MRI) scans of the brain. Early termination scans of participants who discontinued the study after week 36 are considered scans at week 48.
Time Frame Baseline (at least 14 days but not more than 6 weeks prior to Day 1), Weeks 24, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent to Treat 1 (mITT1) population with at least 1 post-baseline PBVC value.
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description:
3 capsules containing placebo were administered orally once daily for at least 48 weeks.
1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.
3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Overall Number of Participants Analyzed 131 128 47
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
Week 24 Number Analyzed 124 participants 121 participants 20 participants
-0.241  (0.8978) -0.042  (0.7537) -0.820  (1.2693)
Week 48 Number Analyzed 114 participants 110 participants 1 participants
-0.455  (0.9770) -0.418  (0.9806) 0.550
3.Secondary Outcome
Title Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) up to Week 48
Hide Description CDP was defined as increase in EDSS of >=1 point from baseline EDSS, if EDSS at entry is ≤5.0 or increase of >=0.5 point, if EDSS at entry is >=5.5. This increase should be confirmed after at least 12 weeks. Progression cannot be confirmed during a protocol defined relapse. EDSS is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. The EDSS scale ranges from 0 to 10 in 0.5 unit increments with 0=no disability and 10=death due to MS. Only an Examining Neurologist administered the EDSS. The Examining Neurologist did not have access to the patient's medical records or source documents, including previous EDSS forms or adverse events. If a patient died due to MS disease progression, the patient was analyzed as having CDP with the time to CDP as the onset date of progression. If a patient died due to MS before having progression, then the time to disability progression was censored using the date of death.
Time Frame Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description:
3 capsules containing placebo were administered orally once daily for at least 48 weeks.
1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.
3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Overall Number of Participants Analyzed 140 139 95
Measure Type: Number
Unit of Measure: percentage of participants
23 17 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Laquinimod 0.6 mg
Comments The statistical model was a Cox proportional hazards regression model with treatment group, categorical EDSS at baseline (≤4.5 or >4.5), age at baseline, natural logarithm of T2 lesion volume at baseline, and country as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.426
Comments significance at 0.05. p-value was from a log-rank test, and estimate and confidence limits were from a Cox model with treatment group as fixed effect, due to the violation of the proportionality assumption.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
0.48 to 1.37
Estimation Comments Laquinimod 0.6 mg vs placebo
4.Secondary Outcome
Title Percentage of Participants With 12-Week Confirmed Disability Progression (CDP) As Measured by Expanded Disability Status Scale (EDSS) or the Timed 25-foot Walk (T25FW) Test up to Week 48
Hide Description

CDP was defined as

increase in EDSS of >=1 point from baseline EDSS, if EDSS at entry is ≤5.0 or increase of >=0.5 point, if EDSS at entry is >=5.5 confirmed after at least 12 weeks, OR increase of >= 20% from baseline in the T25FW test, confirmed after at least 12 weeks.

EDSS quantifies disability in MS and monitors changes in the level of disability over time. The EDSS scale is 0-10 in 0.5 unit increments with 0=no disability and 10=death due to MS. The T25-FW is a quantitative mobility and leg function performance test based on the average time of two trials in which participants walk 25 feet as quickly as possible. Increasing time scores indicate increasing impairment.

If a patient died due to MS disease progression, the patient was analyzed as having CDP with the time to CDP as the onset date of progression. If a patient died due to MS before having progression, then the time to disability progression was censored using the date of death.

Time Frame Baseline (Week 0), Weeks 12, 24, 36, 48 (end if treatment if < 48 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description:
3 capsules containing placebo were administered orally once daily for at least 48 weeks.
1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.
3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Overall Number of Participants Analyzed 140 139 95
Measure Type: Number
Unit of Measure: percentage of participants
34 32 2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Laquinimod 0.6 mg
Comments The statistical model was a Cox proportional hazards regression model with treatment group, categorical EDSS at baseline (≤4.5 or >4.5), age at baseline, natural logarithm of T2 lesion volume at baseline, and country as fixed effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.867
Comments significance at 0.05.
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.68 to 1.59
Estimation Comments Laquinimod 0.6 mg vs placebo
5.Secondary Outcome
Title Change From Baseline for the Timed 25-foot Walk (T25FW) Score at Weeks 12, 24, 36 and 48
Hide Description The T25FW is a quantitative mobility and leg function performance test based on the average time of two trials in which participants walk 25 feet as quickly as possible. In cases when a patient could not complete a T25FW trial due to the physical limitations, a value of 180 seconds was assigned for that trial (this is the maximal possible value for the T25FW test). Increasing time scores indicate increasing impairment. Baseline values are summaries of observed values. Week values are change from baseline values.
Time Frame Baseline (Week 0), Weeks 12, 24, 36, 48
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent to Treat #2 (mITT2) population is a subset of the ITT population. It includes all participants in the ITT population with at least 1 post baseline efficacy assessment other than PBVC.
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description:
3 capsules containing placebo were administered orally once daily for at least 48 weeks.
1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.
3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Overall Number of Participants Analyzed 139 137 89
Median (Full Range)
Unit of Measure: seconds
Baseline Number Analyzed 139 participants 137 participants 89 participants
7.750
(3.15 to 46.00)
7.600
(4.20 to 88.40)
6.850
(4.25 to 62.00)
Week 12 Number Analyzed 135 participants 130 participants 55 participants
0.100
(-8.85 to 16.00)
0.050
(-56.90 to 113.05)
0.100
(-6.15 to 172.00)
Week 24 Number Analyzed 133 participants 127 participants 25 participants
0.100
(-20.50 to 16.85)
0.350
(-58.50 to 113.05)
0.150
(-4.00 to 172.15)
Week 36 Number Analyzed 123 participants 118 participants 4 participants
0.200
(-18.15 to 21.80)
0.450
(-64.60 to 113.05)
12.550
(1.65 to 27.60)
Week 48 Number Analyzed 121 participants 108 participants 0 participants
0.300
(-22.65 to 134.00)
0.050
(-63.50 to 68.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Laquinimod 0.6 mg
Comments placebo n=121 Laquinimod 0.6 mg n=108 The estimate of parameter, standard error, and 95% confidence intervals for change from baseline was from a Mann-Whitney-Wilcoxon Test using Hodges-Lehmann estimates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments significance at 0.05. The p-value for ranked change from baseline values was from a repeated measures analysis of covariance with trt group, week, treatment group by week interaction, rank of T25FW score at baseline, and country as fixed effects.
Method Repeated Measures ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.325
Confidence Interval (2-Sided) 95%
-0.8500 to 0.2000
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.2679
Estimation Comments Laquinimod 0.6 mg vs. placebo treatment effect
6.Secondary Outcome
Title Number of New T2 Brain Lesions at Week 48
Hide Description Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new T2 lesions at week 48 as compared to baseline. Scans of patients who discontinued the study after week 36 are considered scans at week 48, and are included in week 48.
Time Frame Baseline (Week 0), 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat 1 (mITT1) population includes participants with at least 1 post-baseline PBVC value. Participants from the mITT1 with MRI data at week 48 are reported .
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description:
3 capsules containing placebo were administered orally once daily for at least 48 weeks.
1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.
3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Overall Number of Participants Analyzed 119 112 1
Mean (Standard Deviation)
Unit of Measure: lesions
3.5  (10.82) 1.3  (3.01) 1.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Laquinimod 0.6 mg
Comments This analysis was performed using baseline adjusted negative binomial regression model (SAS® PROC GENMOD) in which 1 contrast for comparing laquinimod 0.6 mg to placebo was constructed. In addition to the treatment group, the natural logarithm of T2 lesion volume at baseline, age at baseline and country/geographical region (CGR) were used as covariates.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments significance at 0.05
Method negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.26 to 0.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.11
Estimation Comments Laquinimod 0.6 mg vs. placebo risk ratio
7.Secondary Outcome
Title Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Time Frame Day 1 up to Week 130 (longest duration of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description:
3 capsules containing placebo were administered orally once daily for at least 48 weeks.
1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks.
3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
Overall Number of Participants Analyzed 140 138 95
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
109
  77.9%
115
  83.3%
63
  66.3%
Severe TEAE
6
   4.3%
6
   4.3%
3
   3.2%
Treatment-related TEAE
27
  19.3%
41
  29.7%
29
  30.5%
Deaths
0
   0.0%
0
   0.0%
1
   1.1%
Serious TEAE
6
   4.3%
10
   7.2%
3
   3.2%
Withdrawn from treatment due to TEAE
2
   1.4%
8
   5.8%
4
   4.2%
Time Frame Day 1 up to Week 130 (longest duration of treatment)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Hide Arm/Group Description 3 capsules containing placebo were administered orally once daily for at least 48 weeks. 1 capsule containing 0.6 mg laquinimod and 2 capsules containing placebo were administered orally once daily for at least 48 weeks. 3 capsules containing 0.5 mg laquinimod were administered orally once daily for at least 48 weeks. However this arm was discontinued as of 01 January 2016 and no participants reached the 48 week timeframe.
All-Cause Mortality
Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/140 (0.00%)      0/138 (0.00%)      1/95 (1.05%)    
Hide Serious Adverse Events
Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/140 (4.29%)      10/138 (7.25%)      3/95 (3.16%)    
Cardiac disorders       
Acute myocardial infarction  1  1/140 (0.71%)  1 0/138 (0.00%)  0 0/95 (0.00%)  0
Angina unstable  1  0/140 (0.00%)  0 0/138 (0.00%)  0 1/95 (1.05%)  1
General disorders       
Influenza like illness  1  1/140 (0.71%)  1 0/138 (0.00%)  0 0/95 (0.00%)  0
Oedema peripheral  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Infections and infestations       
Bacterial pyelonephritis  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Pneumonia  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Testicular abscess  1  0/140 (0.00%)  0 0/138 (0.00%)  0 1/95 (1.05%)  1
Urinary tract infection  1  2/140 (1.43%)  2 1/138 (0.72%)  1 0/95 (0.00%)  0
Urosepsis  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Injury, poisoning and procedural complications       
Radius fracture  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Subdural haematoma  1  1/140 (0.71%)  1 0/138 (0.00%)  0 0/95 (0.00%)  0
Investigations       
HIV test positive  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Metabolism and nutrition disorders       
Hypokalaemia  1  1/140 (0.71%)  1 0/138 (0.00%)  0 0/95 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Intervertebral disc disorder  1  1/140 (0.71%)  1 0/138 (0.00%)  0 0/95 (0.00%)  0
Muscle spasms  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Nervous system disorders       
Dizziness  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Facial paralysis  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Lumbosacral plexopathy  1  0/140 (0.00%)  0 0/138 (0.00%)  0 1/95 (1.05%)  1
Multiple sclerosis relapse  1  1/140 (0.71%)  1 1/138 (0.72%)  1 0/95 (0.00%)  0
Neuromyelitis optica spectrum disorder  1  0/140 (0.00%)  0 0/138 (0.00%)  0 1/95 (1.05%)  1
Renal and urinary disorders       
Acute kidney injury  1  1/140 (0.71%)  1 0/138 (0.00%)  0 0/95 (0.00%)  0
Urinary retention  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
Reproductive system and breast disorders       
Uterine haemorrhage  1  0/140 (0.00%)  0 1/138 (0.72%)  1 0/95 (0.00%)  0
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Laquinimod 0.6 mg Laquinimod 1.5 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   77/140 (55.00%)      74/138 (53.62%)      40/95 (42.11%)    
Gastrointestinal disorders       
Abdominal pain upper  1  3/140 (2.14%)  4 5/138 (3.62%)  5 5/95 (5.26%)  5
Constipation  1  6/140 (4.29%)  8 7/138 (5.07%)  7 3/95 (3.16%)  3
Diarrhoea  1  6/140 (4.29%)  7 9/138 (6.52%)  12 1/95 (1.05%)  1
Nausea  1  3/140 (2.14%)  3 4/138 (2.90%)  4 6/95 (6.32%)  6
General disorders       
Fatigue  1  5/140 (3.57%)  5 7/138 (5.07%)  7 3/95 (3.16%)  3
Infections and infestations       
Influenza  1  13/140 (9.29%)  15 7/138 (5.07%)  7 2/95 (2.11%)  2
Nasopharyngitis  1  24/140 (17.14%)  31 24/138 (17.39%)  34 4/95 (4.21%)  4
Upper respiratory tract infection  1  6/140 (4.29%)  7 12/138 (8.70%)  16 2/95 (2.11%)  2
Urinary tract infection  1  11/140 (7.86%)  16 9/138 (6.52%)  13 4/95 (4.21%)  4
Injury, poisoning and procedural complications       
Fall  1  9/140 (6.43%)  13 9/138 (6.52%)  15 4/95 (4.21%)  4
Musculoskeletal and connective tissue disorders       
Arthralgia  1  6/140 (4.29%)  6 8/138 (5.80%)  10 6/95 (6.32%)  8
Back pain  1  15/140 (10.71%)  17 12/138 (8.70%)  15 5/95 (5.26%)  5
Pain in extremity  1  8/140 (5.71%)  8 6/138 (4.35%)  6 1/95 (1.05%)  2
Nervous system disorders       
Headache  1  16/140 (11.43%)  28 14/138 (10.14%)  16 15/95 (15.79%)  18
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.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Teva Pharmaceutical Industries Ltd
Phone: 1-888-483-8279
EMail: USMedInfo@tevapharm.com
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )
ClinicalTrials.gov Identifier: NCT02284568    
Other Study ID Numbers: TV5600-CNS-20006
2014-001579-30 ( EudraCT Number )
First Submitted: October 31, 2014
First Posted: November 6, 2014
Results First Submitted: August 16, 2018
Results First Posted: November 2, 2018
Last Update Posted: November 2, 2018