A Study To Evaluate the Long-Term Safety, Tolerability and Effect on Disease Course

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00988052
• Collaborator: (none)
• Enrollment: 839
• Locations: 135
• Arm: 1
• Actual Duration (Months): 91.7
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to make laquinimod 0.6 mg available for all subjects who completed the placebo-controlled MS-LAQ-301 study according to the protocol and to evaluate the long-term safety, tolerability and effect on disease course of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis.

Condition or Disease	Intervention/Treatment	Phase
Relapsing Multiple Sclerosis	Drug: Laquinimod	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 839 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multinational, Multicenter, Open-label, Single-assignment Extension of the MS-LAQ-301 (ALLEGRO) Study, to Evaluate the Long-term Safety, Tolerability and Effect on Disease Course of Daily Oral Laquinimod 0.6 mg in Subjects With Relapsing MS
• Actual Study Start Date: Nov 10, 2009
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Laquinimod One capsule containing 0.6 mg laquinimod to be administered orally once daily.	Drug: Laquinimod; One capsule containing 0.6 mg laquinimod to be administered orally once daily.

Outcome Measures

Primary Outcome Measures

1. Participants With Treatment-Emergent Adverse Events (TEAEs) [Day 1 up to 7.64 years]

   A treatment-emergent adverse event was defined as any untoward medical occurrence that develops or worsens in severity following start of treatment 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 normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs (SAE) 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. TEAEs associated with cancer, ischemic heart disease, cerebrovascular events, and arthritis were considered to be of special interest.

Secondary Outcome Measures

1. Participants With Potentially Clinically Significant Abnormal Vital Signs [Day 1 up to 7.64 years]

   Vital signs with potentially clinically significant abnormal results were evaluated using the following significance criteria: Pulse rate low: <=45 and decrease >=30 beats/minute Pulse rate high: >=120 and increase >=30 beats/minute Systolic blood pressure low: <=90 and decrease >=30 mmHg Systolic blood pressure high: >=180 and increase >=30 mmHg Diastolic blood pressure low: <=50 and decrease >=20 mmHg Diastolic blood pressure high: >=100 and increase >=20 mmHg

2. Participants With Serum Chemistry Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study [Day 1 up to 7.64 years]

   Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non- PCS value are included in the population count. ALT=alanine aminotransferase ALP=alkaline phosphatase P-amylase=amylase, pancreatic AST=aspartate aminotransferase CRP=C reactive protein CK=creatine kinase CTN=creatinine FIB=fibrinogen GGT=gamma glutamyl transferase K=potassium

3. Participants With Serum Hematology Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study [Day 1 up to 7.64 years]

   Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non- PCS value are included in the population count.

4. Participants With Electrocardiogram (ECG) Fiindings That Shifted From Baseline to Any Time During the Study [Day 1 up to 7.64 years]

   Shifts are presented as Baseline finding / Worse finding at anytime during the study. Categories for findings are: normal abnormal, not clinically significant (Not CS) abnormal, clinically significant (CS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects must have completed the Termination visit of MS-LAQ-301 (completion of all Termination visit activities) according to the MS-LAQ-301 protocol.

2. Women of child-bearing potential must practice an acceptable method of birth control [acceptable methods of birth control in this open label extension phase include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch (or hormone-releasing vaginal ring), long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide)] during the study and up to 30 days after the last dose of the study drug..

3. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.

4. Subjects must be able to comprehend, sign and date a written informed consent prior to entering the MS-LAQ-301E study.

Exclusion Criteria:

1. Premature discontinuation from the MS-LAQ-301 study, for any reason.

2. Pregnancy [according to urine dipstick β-HCG test performed at Baseline (Month 0E) visit] or breastfeeding.

3. Subjects with clinically significant or unstable medical or surgical condition detected or worsened during the MS-LAQ-301 study, which preclude safe participation and completion of the MS-LAQ-301E study. Acute exacerbation of MS will not exclude participation in the MS-LAQ-301E study.

4. Use of inhibitors of CYP3A4 within 2 weeks prior to baseline visit (V0E, Month 0E).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 1076	Phoenix	Arizona	United States	85004
2	Teva Investigational Site 1090	Centennial	Colorado	United States	80112
3	Teva Investigational Site 1088	Fort Collins	Colorado	United States	80528
4	Teva Investigational Site 1102	Northbrook	Illinois	United States	60062
5	Teva Investigational Site 1081	Fort Wayne	Indiana	United States	46845
6	Teva Investigational Site 1083	Des Moines	Iowa	United States	50314
7	Teva Investigational Site 1086	Kansas City	Kansas	United States	66103
8	Teva Investigational Site 1101	Lexington	Kentucky	United States	40513
9	Teva Investigational Site 1096	Farmington Hills	Michigan	United States	48334
10	Teva Investigational Site 1093	Minneapolis	Minnesota	United States	55414
11	Teva Investigational Site 1098	Saint Louis	Missouri	United States	63104
12	Teva Investigational Site 1082	New York	New York	United States	10016
13	Teva Investigational Site 1073	Winston-Salem	North Carolina	United States	27157
14	Teva Investigational Site 1097	Fargo	North Dakota	United States	58103
15	Teva Investigational Site 1084	Dayton	Ohio	United States	45417
16	Teva Investigational Site 1092	Oklahoma City	Oklahoma	United States	73120
17	Teva Investigational Site 1100	Hershey	Pennsylvania	United States	17033-0850
18	Teva Investigational Site 1075	Lubbock	Texas	United States	79410
19	Teva Investigational Site 1078	San Antonio	Texas	United States	78231
20	Teva Investigational Site 1085	Milwaukee	Wisconsin	United States	53215
21	Teva Investigational Site 3300	Klagenfurt		Austria	9020
22	Teva Investigational Site 3303	Linz		Austria	A-4021
23	Teva Investigational Site 3302	Sankt Polten		Austria	3100
24	Teva Investigational Site 5901	Pleven		Bulgaria	5800
25	Teva Investigational Site 5904	Sofia		Bulgaria	1113
26	Teva Investigational Site 5903	Sofia		Bulgaria	1309
27	Teva Investigational Site 5900	Sofia		Bulgaria	1606
28	Teva Investigational Site 5905	Sofia		Bulgaria	1606
29	Teva Investigational Site 5902	Varna		Bulgaria	9010
30	Teva Investigational Site 1132	Bedford	Nova Scotia	Canada	B4A 1A9
31	Teva Investigational Site 1126	London	Ontario	Canada	N6A 5A5
32	Teva Investigational Site 1128	Ottawa	Ontario	Canada	K2G 6E2
33	Teva Investigational Site 1134	Toronto	Ontario	Canada	M4N 3M5
34	Teva Investigational Site 1130	Greenfield Park	Quebec	Canada	J4V 2J2
35	Teva Investigational Site 1129	Montreal	Quebec	Canada	H1T 2M4
36	Teva Investigational Site 1131	Sherbrooke	Quebec	Canada	J1H 5N4
37	Teva Investigational Site 5417	Olomouc		Czechia	779 00
38	Teva Investigational Site 5416	Ostrava - poruba		Czechia	708 52
39	Teva Investigational Site 5504	Tallinn		Estonia	EE-10617
40	Teva Investigational Site 5505	Tartu		Estonia	EE-51014
41	Teva Investigational Site 3525	Besancon		France	25030
42	Teva Investigational Site 3527	Bron Cedex		France	69677
43	Teva Investigational Site 3526	Clermont-Ferrand Cedex 1		France	63003
44	Teva Investigational Site 3524	Lille Cedex		France	59037
45	Teva Investigational Site 3528	Marseille Cedex 5		France	13385
46	Teva Investigational Site 3529	Rennes Cedex 9		France	35033
47	Teva Investigational Site 8100	Tbilisi		Georgia	0112
48	Teva Investigational Site 8101	Tbilisi		Georgia	0179
49	Teva Investigational Site 3247	Bayreuth		Germany	95445
50	Teva Investigational Site 3241	Berlin		Germany	10713
51	Teva Investigational Site 3238	Berlin		Germany	13347
52	Teva Investigational Site 3248	Bochum		Germany	44791
53	Teva Investigational Site 3245	Dresden		Germany	01307
54	Teva Investigational Site 3237	Emden		Germany	26721
55	Teva Investigational Site 3242	Erbach		Germany	64711
56	Teva Investigational Site 3240	Erfurt		Germany	99089
57	Teva Investigational Site 3249	Freiburg		Germany	79106
58	Teva Investigational Site 3236	Hamburg		Germany	20246
59	Teva Investigational Site 3246	Hamburg		Germany	22417
60	Teva Investigational Site 3239	Hannover		Germany	30171
61	Teva Investigational Site 3243	Heidelberg		Germany	69120
62	Teva Investigational Site 3251	Munster		Germany	48149
63	Teva Investigational Site 3250	Trier		Germany	54292
64	Teva Investigational Site 3244	Ulm		Germany	89081
65	Teva Investigational Site 5115	Budapest		Hungary	H-1145
66	Teva Investigational Site 5114	Debrecen		Hungary	4043
67	Teva Investigational Site 5116	Miskolc		Hungary	3526
68	Teva Investigational Site 5117	Veszprem		Hungary	H-8200
69	Teva Investigational Site 8031	Haifa		Israel	3436212
70	Teva Investigational Site 8030	Jerusalem		Israel	9112001
71	Teva Investigational Site 8033	Ramat Gan		Israel	5262160
72	Teva Investigational Site 8032	Tel Aviv		Israel	78278
73	Teva Investigational Site 3044	Catania		Italy	95124
74	Teva Investigational Site 3045	Fidenza		Italy	43036
75	Teva Investigational Site 3042	Gallarate		Italy	21013
76	Teva Investigational Site 3046	Grosseto		Italy	58100
77	Teva Investigational Site 3038	Milano		Italy	20132
78	Teva Investigational Site 555	Milano		Italy	20132
79	Teva Investigational Site 3039	Milano		Italy	20148
80	Teva Investigational Site 3041	Palermo		Italy	90146
81	Teva Investigational Site 3040	Rome		Italy	00133
82	Teva Investigational Site 5704	Kaunas		Lithuania	50009
83	Teva Investigational Site 5705	Siauliai		Lithuania	76231
84	Teva Investigational Site 3810	Nieuwegein		Netherlands	3430 EM
85	Teva Investigational Site 3809	Nijmegen		Netherlands	6525 GC
86	Teva Investigational Site 5322	Czestochowa		Poland	42-280
87	Teva Investigational Site 5320	Gorzow Wielkopolski		Poland	66-400
88	Teva Investigational Site 5316	Katowice		Poland	40-752
89	Teva Investigational Site 5318	Kielce		Poland	25-726
90	Teva Investigational Site 5319	Konskie		Poland	26-200
91	Teva Investigational Site 5317	Krakow		Poland	31-826
92	Teva Investigational Site 5315	Lodz		Poland	90-153
93	Teva Investigational Site 5325	Warszawa		Poland	04-749
94	Teva Investigational Site 5208	Bucharest		Romania	011461
95	Teva Investigational Site 5210	Cluj-Napoca		Romania	400437
96	Teva Investigational Site 5212	Constanta		Romania	900123
97	Teva Investigational Site 5211	Targu-Mures		Romania	540136
98	Teva Investigational Site 5209	Timisoara		Romania	300736
99	Teva Investigational Site 5029	Ekaterinburg		Russian Federation	620102
100	Teva Investigational Site 5021	Moscow		Russian Federation	127015
101	Teva Investigational Site 5028	Nizhny Novgorod		Russian Federation	603126
102	Teva Investigational Site 5027	Novosibirsk		Russian Federation	630087
103	Teva Investigational Site 5030	Perm		Russian Federation	614990
104	Teva Investigational Site 5022	Saint Petersburg		Russian Federation	197022
105	Teva Investigational Site 5025	St. Petersburg		Russian Federation	194044
106	Teva Investigational Site 5024	St. Petersburg		Russian Federation	194354
107	Teva Investigational Site 5023	St. Petersburg		Russian Federation	197376
108	Teva Investigational Site 5026	St.Petersburg		Russian Federation	191186
109	Teva Investigational Site 6100	Belgrade		Serbia	11000
110	Teva Investigational Site 6102	Nis		Serbia	18 000
111	Teva Investigational Site 3132	Barcelona		Spain	08035
112	Teva Investigational Site 3134	Barcelona		Spain	08036
113	Teva Investigational Site 3144	Barcelona		Spain	08041
114	Teva Investigational Site 3140	Beade-Pontevedra		Spain	36312
115	Teva Investigational Site 3142	Getafe		Spain	28905
116	Teva Investigational Site 3135	Lleida		Spain	25198
117	Teva Investigational Site 3133	Madrid		Spain	28040
118	Teva Investigational Site 3146	Madrid		Spain	28046
119	Teva Investigational Site 3137	Murcia		Spain	30120
120	Teva Investigational Site 3138	Pontevedra		Spain	36001
121	Teva Investigational Site 3136	Salt		Spain	17190
122	Teva Investigational Site 3139	Santiago de Compostela		Spain	15706
123	Teva Investigational Site 3143	Valencia		Spain	46010
124	Teva Investigational Site 4204	Stockholm		Sweden	14186
125	Teva Investigational Site 4205	Stockholm		Sweden	17176
126	Teva Investigational Site 4206	Stockholm		Sweden	18288
127	Teva Investigational Site 8201	Izmir		Turkey	35340
128	Teva Investigational Site 5803	Dnipropetrovsk		Ukraine	49027
129	Teva Investigational Site 5802	Kyiv		Ukraine	03110
130	Teva Investigational Site 5804	Kyiv		Ukraine	03115
131	Teva Investigational Site 5800	Lviv		Ukraine	79010
132	Teva Investigational Site 5801	Vinnytsya		Ukraine	21005
133	Teva Investigational Site 3425	Liverpool		United Kingdom	L9 7LJ
134	Teva Investigational Site 3424	London		United Kingdom	E1 2AT
135	Teva Investigational Site 3422	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Principal Investigator: Giancarlo Comi, Prof., MD, U.O.Neurology-Neurorehabilitation and Clinical Neurophysiology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 25, 2016

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT00988052
• Other Study ID Numbers: MS-LAQ-301E; 2009-012989-30
• First Posted: Oct 1, 2009
• Last Update Posted: Dec 9, 2021
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Teva Branded Pharmaceutical Products R&D, Inc.: Relapsing Multiple Sclerosis
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Disease Progression

Study Results

Participant Flow

Recruitment Details	In the preceding double-blind, placebo-controlled ALLEGRO study (study MS-LAQ-301), 1106 subjects with RRMS were randomized to treatment, and 864 subjects completed the study according to the protocol (ie, by completing the ALLEGRO study termination visit procedures).
Pre-assignment Detail	In this open-label extension study, 839 subjects with RRMS were enrolled to receive laquinimod 0.6 mg at 135 study sites in 22 countries by 135 investigators.

Arm/Group Title	Early Laquinimod	Switch From Placebo
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.
Period Title: Overall Study
STARTED	423	416
COMPLETED	0	0
NOT COMPLETED	423	416

Baseline Characteristics

Arm/Group Title	Early Laquinimod	Switch From Placebo	Total
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.	Total of all reporting groups
Overall Participants	423	416	839
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.1 (9.10)	40.5 (9.14)	40.8 (9.12)
Sex: Female, Male (Count of Participants)
Female	298 70.4%	271 65.1%	569 67.8%
Male	125 29.6%	145 34.9%	270 32.2%
Race/Ethnicity, Customized (Count of Participants)
Asian / Oriental	2 0.5%	0 0%	2 0.2%
Black / African American	1 0.2%	5 1.2%	6 0.7%
Caucasian	414 97.9%	401 96.4%	815 97.1%
Other	2 0.5%	2 0.5%	4 0.5%
Missing	1 0.2%	2 0.5%	3 0.4%
Unknown	3 0.7%	6 1.4%	9 1.1%

Outcome Measures

1. Primary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	A treatment-emergent adverse event was defined as any untoward medical occurrence that develops or worsens in severity following start of treatment 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 normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs (SAE) 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. TEAEs associated with cancer, ischemic heart disease, cerebrovascular events, and arthritis were considered to be of special interest.
Time Frame	Day 1 up to 7.64 years

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	Early Laquinimod	Switch From Placebo
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.
Measure Participants	423	416
=>1 TEAE	375 88.7%	374 89.9%
=>1 Severe TEAE	76 18%	69 16.6%
=>1 TEAE of special interest	109 25.8%	105 25.2%
=>1 treatment-related TEAE	139 32.9%	153 36.8%
=>1 TEAE leading to death	3 0.7%	3 0.7%
=>1 Serious TEAE	108 25.5%	92 22.1%
=>1 TEAE causing discontinuation	35 8.3%	32 7.7%

2. Secondary Outcome

Title	Participants With Potentially Clinically Significant Abnormal Vital Signs
Description	Vital signs with potentially clinically significant abnormal results were evaluated using the following significance criteria: Pulse rate low: <=45 and decrease >=30 beats/minute Pulse rate high: >=120 and increase >=30 beats/minute Systolic blood pressure low: <=90 and decrease >=30 mmHg Systolic blood pressure high: >=180 and increase >=30 mmHg Diastolic blood pressure low: <=50 and decrease >=20 mmHg Diastolic blood pressure high: >=100 and increase >=20 mmHg
Time Frame	Day 1 up to 7.64 years

Outcome Measure Data

Analysis Population Description

Safety analysis set of participants with a baseline and post-baseline value for that vital sign.

Arm/Group Title	Early Laquinimod	Switch From Placebo
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.
Measure Participants	423	416
Participants with at least one abnormality	36 8.5%	34 8.2%
Pulse rate - low	1 0.2%	1 0.2%
Pulse rate - high	2 0.5%	1 0.2%
Systolic blood pressure - low	20 4.7%	10 2.4%
Systolic blood pressure - high	1 0.2%	2 0.5%
Diastolic blood pressure - low	7 1.7%	7 1.7%
Diastolic blood pressure - high	8 1.9%	14 3.4%

3. Secondary Outcome

Title	Participants With Serum Chemistry Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study
Description	Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non- PCS value are included in the population count. ALT=alanine aminotransferase ALP=alkaline phosphatase P-amylase=amylase, pancreatic AST=aspartate aminotransferase CRP=C reactive protein CK=creatine kinase CTN=creatinine FIB=fibrinogen GGT=gamma glutamyl transferase K=potassium
Time Frame	Day 1 up to 7.64 years

Outcome Measure Data

Analysis Population Description

Safety analysis set of participants with both a baseline and a post-baseline value for the test.

Arm/Group Title	Early Laquinimod	Switch From Placebo
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.
Measure Participants	422	415
ALT - change from Low / Non- PCS to High PCS	8 1.9%	14 3.4%
Albumen - change from High / Non-PCS to Low PCS	1 0.2%	0 0%
ALP - change from Low / Non- PCS to High PCS	3 0.7%	0 0%
p-Amylase - change from Low / Non-PCS to High PCS	2 0.5%	6 1.4%
AST - change from Low / Non- PCS to High PCS	4 0.9%	5 1.2%
CRP - change from Low / Non- PCS to High PCS	41 9.7%	51 12.3%
Calcium - change from High / Non-PCS to Low PCS	1 0.2%	4 1%
Calcium - change from Low / Non-PCS to High PCS	1 0.2%	2 0.5%
CK - change from Low / Non- PCS to High PCS	16 3.8%	17 4.1%
CTN - change from Low / Non- PCS to High PCS	2 0.5%	2 0.5%
FIB - change from Low / Non- PCS to High PCS	37 8.7%	38 9.1%
GGT - change from Low / Non- PCS to High PCS	33 7.8%	24 5.8%
Glucose - change from High / Non-PCS to Low PCS	23 5.4%	27 6.5%
Glucose - change from Low / Non-PCS to High PCS	9 2.1%	5 1.2%
Phosphate-change from High / Non-PCS to Low PCS	14 3.3%	15 3.6%
Phosphate-change from Low / Non-PCS to High PCS	19 4.5%	16 3.8%
K - change from High / Non- PCS to Low PCS	4 0.9%	3 0.7%
K - change from Low / Non- PCS to High PCS	46 10.9%	55 13.2%
Sodium - change from High / Non-PCS to Low PCS	8 1.9%	3 0.7%
Sodium - change from Low / Non-PCS to High PCS	13 3.1%	17 4.1%
Urea - change from Low / Non- PCS to High PCS	3 0.7%	4 1%

4. Secondary Outcome

Title	Participants With Serum Hematology Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study
Description	Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non- PCS value are included in the population count.
Time Frame	Day 1 up to 7.64 years

Outcome Measure Data

Analysis Population Description

Safety analysis set of participants with both a baseline and a post-baseline value for the test.

Arm/Group Title	Early Laquinimod	Switch From Placebo
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.
Measure Participants	422	415
Hematocrit - change from High / Non-PCS to Low PCS	36 8.5%	29 7%
Hemoglobin -change from High / Non-PCS to Low PCS	27 6.4%	22 5.3%
Hemoglobin -change from Low / Non-PCS to High PCS	0 0%	1 0.2%
Leukocytes - change from High / Non-PCS to Low PCS	1 0.2%	1 0.2%
Leukocytes - change from Low / Non-PCS to High PCS	4 0.9%	3 0.7%
Neutrophils - change from High/Non-PCS to Low PCS	15 3.5%	12 2.9%
Platelets - change from High / Non-PCS to Low PCS	4 0.9%	7 1.7%
Platelets - change from Low / Non-PCS to High PCS	2 0.5%	6 1.4%

5. Secondary Outcome

Title	Participants With Electrocardiogram (ECG) Fiindings That Shifted From Baseline to Any Time During the Study
Description	Shifts are presented as Baseline finding / Worse finding at anytime during the study. Categories for findings are: normal abnormal, not clinically significant (Not CS) abnormal, clinically significant (CS)
Time Frame	Day 1 up to 7.64 years

Outcome Measure Data

Analysis Population Description

Safety analysis set of participants with both a baseline and a post-baseline ECG.

Arm/Group Title	Early Laquinimod	Switch From Placebo
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.
Measure Participants	420	412
Normal / Normal	189 44.7%	198 47.6%
Normal / Abnormal, Not CS	145 34.3%	126 30.3%
Normal / Abnormal, CS	2 0.5%	3 0.7%
Abnormal, Not CS / Normal	12 2.8%	14 3.4%
Abnormal, Not CS / Abnormal, Not CS	70 16.5%	67 16.1%
Abnormal, Not CS / Abnormal, CS	2 0.5%	4 1%
Abnormal, CS / Normal	0 0%	0 0%
Abnormal, CS / Abnormal, Not CS	0 0%	0 0%
Abnormal, CS / Abnormal, CS	0 0%	0 0%

Adverse Events

Time Frame	Day 1 up to 7.64 years
Arm/Group Title	Early Laquinimod 0.6 mg		Switch From Placebo to Laquinimod 0.6 mg
Arm/Group Description	All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Early laquinimod subgroup included participants in MS-LAQ-301 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.		All participants in MS-LAQ-301E were administered 1 capsule containing laquinimod 0.6 mg taken orally at the same hour every day until the product was commercially available or development stopped. The Switch from placebo subgroup included participants in MS-LAQ-301 double-blind study who were administered placebo daily for 24 months.
All Cause Mortality
	Early Laquinimod 0.6 mg		Switch From Placebo to Laquinimod 0.6 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/423 (0.7%)		3/416 (0.7%)
Serious Adverse Events
	Early Laquinimod 0.6 mg		Switch From Placebo to Laquinimod 0.6 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	108/423 (25.5%)		92/416 (22.1%)
Blood and lymphatic system disorders
Anaemia	1/423 (0.2%)	1	1/416 (0.2%)	1
Bone marrow oedema	1/423 (0.2%)	1	0/416 (0%)	0
Lymphadenitis	0/423 (0%)	0	1/416 (0.2%)	1
Cardiac disorders
Acute coronary syndrome	1/423 (0.2%)	1	1/416 (0.2%)	1
Acute myocardial infarction	1/423 (0.2%)	1	1/416 (0.2%)	1
Angina pectoris	1/423 (0.2%)	1	0/416 (0%)	0
Angina unstable	1/423 (0.2%)	1	2/416 (0.5%)	2
Atrial fibrillation	2/423 (0.5%)	2	0/416 (0%)	0
Cardiac failure chronic	1/423 (0.2%)	1	1/416 (0.2%)	1
Cardiac failure congestive	1/423 (0.2%)	1	0/416 (0%)	0
Coronary artery stenosis	0/423 (0%)	0	1/416 (0.2%)	1
Mitral valve incompetence	1/423 (0.2%)	1	0/416 (0%)	0
Myocardial infarction	2/423 (0.5%)	2	2/416 (0.5%)	2
Myocardial ischaemia	1/423 (0.2%)	1	0/416 (0%)	0
Pericarditis	1/423 (0.2%)	1	0/416 (0%)	0
Silent myocardial infarction	0/423 (0%)	0	1/416 (0.2%)	1
Ventricular extrasystoles	1/423 (0.2%)	1	0/416 (0%)	0
Ventricular tachycardia	1/423 (0.2%)	1	0/416 (0%)	0
Ear and labyrinth disorders
Deafness	1/423 (0.2%)	1	0/416 (0%)	0
Vertigo	0/423 (0%)	0	1/416 (0.2%)	1
Endocrine disorders
Goitre	1/423 (0.2%)	1	0/416 (0%)	0
Hyperparathyroidism primary	1/423 (0.2%)	1	0/416 (0%)	0
Parathyroid gland enlargement	1/423 (0.2%)	1	0/416 (0%)	0
Eye disorders
Blindness unilateral	0/423 (0%)	0	1/416 (0.2%)	1
Eye haemorrhage	1/423 (0.2%)	1	0/416 (0%)	0
Uveitis	0/423 (0%)	0	1/416 (0.2%)	1
Gastrointestinal disorders
Abdominal adhesions	0/423 (0%)	0	1/416 (0.2%)	1
Abdominal hernia	1/423 (0.2%)	1	0/416 (0%)	0
Abdominal pain	1/423 (0.2%)	1	1/416 (0.2%)	1
Abdominal pain upper	1/423 (0.2%)	1	1/416 (0.2%)	1
Constipation	0/423 (0%)	0	1/416 (0.2%)	1
Diarrhoea	0/423 (0%)	0	1/416 (0.2%)	1
Dysphagia	0/423 (0%)	0	1/416 (0.2%)	1
Gastric ulcer	0/423 (0%)	0	1/416 (0.2%)	1
Gastritis	1/423 (0.2%)	1	0/416 (0%)	0
Gastrooesophageal reflux disease	0/423 (0%)	0	2/416 (0.5%)	2
Hiatus hernia	2/423 (0.5%)	2	0/416 (0%)	0
Ileus	0/423 (0%)	0	1/416 (0.2%)	1
Inguinal hernia	0/423 (0%)	0	1/416 (0.2%)	1
Intestinal obstruction	1/423 (0.2%)	1	1/416 (0.2%)	1
Irritable bowel syndrome	0/423 (0%)	0	1/416 (0.2%)	1
Omental infarction	0/423 (0%)	0	1/416 (0.2%)	1
Pancreatitis	1/423 (0.2%)	1	0/416 (0%)	0
Pancreatitis chronic	1/423 (0.2%)	1	0/416 (0%)	0
Small intestinal obstruction	1/423 (0.2%)	1	0/416 (0%)	0
Volvulus	0/423 (0%)	0	1/416 (0.2%)	1
Vomiting	0/423 (0%)	0	1/416 (0.2%)	1
General disorders
Asthenia	1/423 (0.2%)	1	0/416 (0%)	0
Chest discomfort	1/423 (0.2%)	1	0/416 (0%)	0
Chest pain	2/423 (0.5%)	2	0/416 (0%)	0
Death	0/423 (0%)	0	1/416 (0.2%)	1
Drowning	1/423 (0.2%)	1	0/416 (0%)	0
Fatigue	1/423 (0.2%)	1	0/416 (0%)	0
Gait disturbance	1/423 (0.2%)	1	0/416 (0%)	0
Impaired healing	1/423 (0.2%)	1	0/416 (0%)	0
Inflammation	0/423 (0%)	0	1/416 (0.2%)	1
Influenza like illness	0/423 (0%)	0	1/416 (0.2%)	1
Medical device pain	1/423 (0.2%)	1	0/416 (0%)	0
Non-cardiac chest pain	0/423 (0%)	0	1/416 (0.2%)	2
Pyrexia	1/423 (0.2%)	1	0/416 (0%)	0
Systemic inflammatory response syndrome	1/423 (0.2%)	1	0/416 (0%)	0
Hepatobiliary disorders
Autoimmune hepatitis	0/423 (0%)	0	1/416 (0.2%)	1
Biliary colic	1/423 (0.2%)	1	0/416 (0%)	0
Cholecystitis	0/423 (0%)	0	1/416 (0.2%)	1
Cholecystitis acute	1/423 (0.2%)	1	0/416 (0%)	0
Cholelithiasis	2/423 (0.5%)	2	1/416 (0.2%)	1
Cholestasis	0/423 (0%)	0	1/416 (0.2%)	1
Hepatitis	1/423 (0.2%)	1	0/416 (0%)	0
Hepatotoxicity	0/423 (0%)	0	1/416 (0.2%)	1
Hydrocholecystis	1/423 (0.2%)	1	0/416 (0%)	0
Immune system disorders
Drug hypersensitivity	1/423 (0.2%)	1	0/416 (0%)	0
Infections and infestations
Abdominal abscess	0/423 (0%)	0	1/416 (0.2%)	1
Abscess limb	1/423 (0.2%)	1	0/416 (0%)	0
Acute sinusitis	1/423 (0.2%)	1	0/416 (0%)	0
Appendicitis	4/423 (0.9%)	4	3/416 (0.7%)	3
Appendicitis perforated	2/423 (0.5%)	2	1/416 (0.2%)	1
Bartholin's abscess	1/423 (0.2%)	2	0/416 (0%)	0
Breast abscess	1/423 (0.2%)	2	0/416 (0%)	0
Cellulitis	1/423 (0.2%)	1	1/416 (0.2%)	1
Cholecystitis infective	1/423 (0.2%)	1	0/416 (0%)	0
Chronic tonsillitis	1/423 (0.2%)	1	0/416 (0%)	0
Cytomegalovirus infection	0/423 (0%)	0	1/416 (0.2%)	1
Diverticulitis	0/423 (0%)	0	1/416 (0.2%)	1
Escherichia urinary tract infection	1/423 (0.2%)	1	0/416 (0%)	0
Furuncle	1/423 (0.2%)	1	0/416 (0%)	0
Groin abscess	2/423 (0.5%)	2	0/416 (0%)	0
Hepatic echinococciasis	0/423 (0%)	0	1/416 (0.2%)	2
Influenza	0/423 (0%)	0	1/416 (0.2%)	1
Latent syphilis	1/423 (0.2%)	1	0/416 (0%)	0
Latent tuberculosis	0/423 (0%)	0	1/416 (0.2%)	1
Meningitis viral	0/423 (0%)	0	1/416 (0.2%)	2
Mycotoxicosis	1/423 (0.2%)	1	0/416 (0%)	0
Nasopharyngitis	0/423 (0%)	0	1/416 (0.2%)	1
Otitis media chronic	1/423 (0.2%)	1	0/416 (0%)	0
Ovarian abscess	1/423 (0.2%)	1	0/416 (0%)	0
Peritonitis	4/423 (0.9%)	4	0/416 (0%)	0
Periumbilical abscess	1/423 (0.2%)	1	0/416 (0%)	0
Pertussis	0/423 (0%)	0	1/416 (0.2%)	1
Pharyngeal abscess	0/423 (0%)	0	1/416 (0.2%)	1
Pilonidal cyst	1/423 (0.2%)	1	0/416 (0%)	0
Pneumonia	1/423 (0.2%)	1	3/416 (0.7%)	4
Postoperative wound infection	1/423 (0.2%)	1	0/416 (0%)	0
Pyelonephritis	0/423 (0%)	0	1/416 (0.2%)	1
Pyelonephritis acute	1/423 (0.2%)	1	1/416 (0.2%)	1
Pyelonephritis chronic	0/423 (0%)	0	1/416 (0.2%)	1
Salpingo-oophoritis	1/423 (0.2%)	1	0/416 (0%)	0
Staphylococcal infection	1/423 (0.2%)	1	0/416 (0%)	0
Subcutaneous abscess	1/423 (0.2%)	1	0/416 (0%)	0
Tonsillitis	0/423 (0%)	0	1/416 (0.2%)	1
Tubo-ovarian abscess	1/423 (0.2%)	1	0/416 (0%)	0
Urinary tract infection	2/423 (0.5%)	2	1/416 (0.2%)	1
Urosepsis	1/423 (0.2%)	1	0/416 (0%)	0
Vestibular neuronitis	0/423 (0%)	0	1/416 (0.2%)	1
Injury, poisoning and procedural complications
Accidental overdose	1/423 (0.2%)	1	0/416 (0%)	0
Ankle fracture	1/423 (0.2%)	1	0/416 (0%)	0
Brain contusion	0/423 (0%)	0	1/416 (0.2%)	1
Comminuted fracture	0/423 (0%)	0	1/416 (0.2%)	2
Facial bones fracture	1/423 (0.2%)	1	0/416 (0%)	0
Fall	6/423 (1.4%)	6	0/416 (0%)	0
Femur fracture	2/423 (0.5%)	2	0/416 (0%)	0
Foot fracture	1/423 (0.2%)	1	0/416 (0%)	0
Hip fracture	1/423 (0.2%)	1	0/416 (0%)	0
Humerus fracture	1/423 (0.2%)	1	0/416 (0%)	0
Joint dislocation	1/423 (0.2%)	1	0/416 (0%)	0
Lower limb fracture	1/423 (0.2%)	1	0/416 (0%)	0
Meniscus injury	1/423 (0.2%)	1	0/416 (0%)	0
Postoperative wound complication	1/423 (0.2%)	1	0/416 (0%)	0
Procedural complication	1/423 (0.2%)	1	0/416 (0%)	0
Radius fracture	0/423 (0%)	0	1/416 (0.2%)	1
Road traffic accident	0/423 (0%)	0	2/416 (0.5%)	2
Seroma	1/423 (0.2%)	1	0/416 (0%)	0
Skull fracture	0/423 (0%)	0	1/416 (0.2%)	1
Tendon rupture	1/423 (0.2%)	1	0/416 (0%)	0
Tibia fracture	1/423 (0.2%)	1	1/416 (0.2%)	1
Investigations
C-reactive protein increased	4/423 (0.9%)	4	1/416 (0.2%)	1
Gamma-glutamyltransferase increased	0/423 (0%)	0	1/416 (0.2%)	1
Hepatic enzyme increased	1/423 (0.2%)	1	0/416 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/423 (0.2%)	1	0/416 (0%)	0
Hypercalcaemia	1/423 (0.2%)	1	0/416 (0%)	0
Hypokalaemia	1/423 (0.2%)	2	0/416 (0%)	0
Obesity	1/423 (0.2%)	1	0/416 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/423 (0.2%)	1	1/416 (0.2%)	1
Arthritis	0/423 (0%)	0	1/416 (0.2%)	1
Back pain	0/423 (0%)	0	1/416 (0.2%)	1
Bone pain	1/423 (0.2%)	1	0/416 (0%)	0
Bursitis	1/423 (0.2%)	1	0/416 (0%)	0
Cervical spinal stenosis	1/423 (0.2%)	1	0/416 (0%)	0
Groin pain	1/423 (0.2%)	1	0/416 (0%)	0
Intervertebral disc protrusion	2/423 (0.5%)	3	3/416 (0.7%)	3
Intervertebral disc space narrowing	1/423 (0.2%)	1	0/416 (0%)	0
Joint hyperextension	1/423 (0.2%)	2	0/416 (0%)	0
Joint instability	2/423 (0.5%)	2	0/416 (0%)	0
Knee impingement syndrome	0/423 (0%)	0	1/416 (0.2%)	1
Lumbar spinal stenosis	0/423 (0%)	0	2/416 (0.5%)	2
Neck pain	0/423 (0%)	0	1/416 (0.2%)	1
Osteoarthritis	1/423 (0.2%)	1	0/416 (0%)	0
Osteochondrosis	0/423 (0%)	0	1/416 (0.2%)	1
Osteonecrosis	1/423 (0.2%)	1	1/416 (0.2%)	1
Pseudarthrosis	1/423 (0.2%)	2	1/416 (0.2%)	1
Rheumatoid arthritis	1/423 (0.2%)	3	0/416 (0%)	0
Rotator cuff syndrome	0/423 (0%)	0	1/416 (0.2%)	1
Spinal pain	0/423 (0%)	0	1/416 (0.2%)	1
Spondylolisthesis	0/423 (0%)	0	1/416 (0.2%)	1
Tendon calcification	1/423 (0.2%)	1	0/416 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	1/423 (0.2%)	1	0/416 (0%)	0
B-cell lymphoma	0/423 (0%)	0	1/416 (0.2%)	1
Basal cell carcinoma	0/423 (0%)	0	1/416 (0.2%)	1
Benign neoplasm of thyroid gland	0/423 (0%)	0	1/416 (0.2%)	1
Benign ovarian tumour	1/423 (0.2%)	1	0/416 (0%)	0
Breast cancer	2/423 (0.5%)	2	1/416 (0.2%)	1
Breast cancer stage II	1/423 (0.2%)	1	0/416 (0%)	0
Cervix carcinoma stage 0	1/423 (0.2%)	1	0/416 (0%)	0
Chronic lymphocytic leukaemia stage 1	1/423 (0.2%)	1	1/416 (0.2%)	1
Fibroadenoma of breast	1/423 (0.2%)	1	0/416 (0%)	0
Hodgkin's disease	0/423 (0%)	0	1/416 (0.2%)	1
Intraductal proliferative breast lesion	0/423 (0%)	0	1/416 (0.2%)	1
Invasive breast carcinoma	1/423 (0.2%)	1	0/416 (0%)	0
Invasive ductal breast carcinoma	0/423 (0%)	0	1/416 (0.2%)	1
Keratoacanthoma	0/423 (0%)	0	1/416 (0.2%)	1
Langerhans' cell histiocytosis	1/423 (0.2%)	1	0/416 (0%)	0
Lung adenocarcinoma metastatic	1/423 (0.2%)	2	0/416 (0%)	0
Metastases to central nervous system	1/423 (0.2%)	2	0/416 (0%)	0
Metastases to lung	1/423 (0.2%)	1	0/416 (0%)	0
Oncocytoma	1/423 (0.2%)	1	0/416 (0%)	0
Ovarian adenoma	1/423 (0.2%)	1	0/416 (0%)	0
Ovarian cancer metastatic	0/423 (0%)	0	1/416 (0.2%)	1
Papillary thyroid cancer	1/423 (0.2%)	1	0/416 (0%)	0
Renal cancer	1/423 (0.2%)	1	0/416 (0%)	0
Small cell lung cancer metastatic	1/423 (0.2%)	1	0/416 (0%)	0
Squamous cell carcinoma of skin	1/423 (0.2%)	1	0/416 (0%)	0
Tubular breast carcinoma	1/423 (0.2%)	1	0/416 (0%)	0
Uterine leiomyoma	3/423 (0.7%)	3	4/416 (1%)	4
Vulval cancer	0/423 (0%)	0	1/416 (0.2%)	1
Nervous system disorders
Carotid artery stenosis	0/423 (0%)	0	1/416 (0.2%)	2
Carpal tunnel syndrome	1/423 (0.2%)	1	0/416 (0%)	0
Cerebral artery occlusion	1/423 (0.2%)	1	0/416 (0%)	0
Cerebral haemorrhage	0/423 (0%)	0	1/416 (0.2%)	1
Cerebrovascular accident	0/423 (0%)	0	1/416 (0.2%)	1
Cervicobrachial syndrome	0/423 (0%)	0	1/416 (0.2%)	1
Epilepsy	3/423 (0.7%)	3	0/416 (0%)	0
Headache	1/423 (0.2%)	1	1/416 (0.2%)	1
Hypoaesthesia	1/423 (0.2%)	1	0/416 (0%)	0
Ischaemic stroke	1/423 (0.2%)	1	0/416 (0%)	0
Lethargy	1/423 (0.2%)	1	0/416 (0%)	0
Lumbar radiculopathy	1/423 (0.2%)	1	0/416 (0%)	0
Multiple sclerosis relapse	3/423 (0.7%)	3	2/416 (0.5%)	2
Optic neuritis	0/423 (0%)	0	1/416 (0.2%)	1
Paraesthesia	1/423 (0.2%)	1	0/416 (0%)	0
Sciatica	0/423 (0%)	0	1/416 (0.2%)	1
Simple partial seizures	1/423 (0.2%)	1	0/416 (0%)	0
Syncope	3/423 (0.7%)	3	1/416 (0.2%)	1
Transient ischaemic attack	0/423 (0%)	0	1/416 (0.2%)	1
Trigeminal neuralgia	1/423 (0.2%)	1	1/416 (0.2%)	1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/423 (0.2%)	1	3/416 (0.7%)	3
Psychiatric disorders
Agoraphobia	1/423 (0.2%)	1	0/416 (0%)	0
Anxiety	1/423 (0.2%)	1	0/416 (0%)	0
Completed suicide	0/423 (0%)	0	1/416 (0.2%)	1
Depression	0/423 (0%)	0	2/416 (0.5%)	2
Mood disorder due to a general medical condition	1/423 (0.2%)	1	0/416 (0%)	0
Neurosis	1/423 (0.2%)	1	0/416 (0%)	0
Panic disorder	1/423 (0.2%)	1	0/416 (0%)	0
Substance-induced psychotic disorder	0/423 (0%)	0	1/416 (0.2%)	1
Suicide attempt	1/423 (0.2%)	1	0/416 (0%)	0
Renal and urinary disorders
Bladder dysfunction	1/423 (0.2%)	1	0/416 (0%)	0
Calculus urinary	0/423 (0%)	0	1/416 (0.2%)	1
Chronic kidney disease	1/423 (0.2%)	1	0/416 (0%)	0
Haematuria	1/423 (0.2%)	1	0/416 (0%)	0
Hydronephrosis	0/423 (0%)	0	2/416 (0.5%)	2
Ketonuria	1/423 (0.2%)	1	0/416 (0%)	0
Nephrolithiasis	2/423 (0.5%)	2	1/416 (0.2%)	1
Tubulointerstitial nephritis	1/423 (0.2%)	1	0/416 (0%)	0
Urethral meatus stenosis	0/423 (0%)	0	1/416 (0.2%)	1
Urethral stenosis	0/423 (0%)	0	1/416 (0.2%)	1
Urinary incontinence	1/423 (0.2%)	1	0/416 (0%)	0
Urinary retention	0/423 (0%)	0	1/416 (0.2%)	1
Reproductive system and breast disorders
Acquired hydrocele	0/423 (0%)	0	1/416 (0.2%)	1
Endometrial hyperplasia	0/423 (0%)	0	1/416 (0.2%)	1
Endometriosis	1/423 (0.2%)	2	2/416 (0.5%)	2
Fibrocystic breast disease	1/423 (0.2%)	1	0/416 (0%)	0
Hydrosalpinx	1/423 (0.2%)	1	0/416 (0%)	0
Menometrorrhagia	0/423 (0%)	0	1/416 (0.2%)	1
Metrorrhagia	1/423 (0.2%)	1	0/416 (0%)	0
Ovarian cyst	1/423 (0.2%)	1	1/416 (0.2%)	1
Uterine polyp	1/423 (0.2%)	1	1/416 (0.2%)	1
Uterine prolapse	0/423 (0%)	0	1/416 (0.2%)	2
Vaginal prolapse	0/423 (0%)	0	1/416 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/423 (0%)	0	1/416 (0.2%)	1
Bronchiectasis	1/423 (0.2%)	1	0/416 (0%)	0
Bronchitis chronic	0/423 (0%)	0	1/416 (0.2%)	2
Dyspnoea	2/423 (0.5%)	3	0/416 (0%)	0
Nasal polyps	0/423 (0%)	0	1/416 (0.2%)	1
Nasal septum deviation	2/423 (0.5%)	2	0/416 (0%)	0
Pharyngeal polyp	0/423 (0%)	0	1/416 (0.2%)	1
Pleural effusion	1/423 (0.2%)	1	1/416 (0.2%)	1
Pleurisy	0/423 (0%)	0	1/416 (0.2%)	1
Pneumothorax	1/423 (0.2%)	1	0/416 (0%)	0
Pulmonary embolism	1/423 (0.2%)	1	1/416 (0.2%)	1
Skin and subcutaneous tissue disorders
Hidradenitis	1/423 (0.2%)	1	0/416 (0%)	0
Surgical and medical procedures
Cholecystectomy	1/423 (0.2%)	1	0/416 (0%)	0
Hysterectomy	0/423 (0%)	0	1/416 (0.2%)	1
Intervertebral disc operation	0/423 (0%)	0	1/416 (0.2%)	1
Knee arthroplasty	1/423 (0.2%)	1	0/416 (0%)	0
Nephrectomy	1/423 (0.2%)	1	0/416 (0%)	0
Spinal fusion surgery	1/423 (0.2%)	1	0/416 (0%)	0
Vascular disorders
Deep vein thrombosis	0/423 (0%)	0	1/416 (0.2%)	1
Hypertension	0/423 (0%)	0	1/416 (0.2%)	1
Hypertensive crisis	0/423 (0%)	0	2/416 (0.5%)	2
Hypotension	0/423 (0%)	0	1/416 (0.2%)	1
Peripheral artery stenosis	0/423 (0%)	0	1/416 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Early Laquinimod 0.6 mg		Switch From Placebo to Laquinimod 0.6 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	299/423 (70.7%)		300/416 (72.1%)
Blood and lymphatic system disorders
Anaemia	22/423 (5.2%)	25	16/416 (3.8%)	17
Gastrointestinal disorders
Abdominal pain upper	19/423 (4.5%)	23	31/416 (7.5%)	39
Diarrhoea	24/423 (5.7%)	31	21/416 (5%)	23
Nausea	24/423 (5.7%)	27	26/416 (6.3%)	37
General disorders
Fatigue	25/423 (5.9%)	30	31/416 (7.5%)	38
Infections and infestations
Bronchitis	33/423 (7.8%)	44	33/416 (7.9%)	46
Influenza	28/423 (6.6%)	41	34/416 (8.2%)	46
Nasopharyngitis	106/423 (25.1%)	169	112/416 (26.9%)	210
Sinusitis	27/423 (6.4%)	36	28/416 (6.7%)	47
Upper respiratory tract infection	43/423 (10.2%)	69	41/416 (9.9%)	65
Urinary tract infection	55/423 (13%)	110	39/416 (9.4%)	76
Injury, poisoning and procedural complications
Fall	20/423 (4.7%)	30	23/416 (5.5%)	30
Investigations
Alanine aminotransferase increased	13/423 (3.1%)	16	22/416 (5.3%)	27
C-reactive protein increased	26/423 (6.1%)	31	31/416 (7.5%)	37
Gamma-glutamyltransferase increased	22/423 (5.2%)	27	16/416 (3.8%)	23
Musculoskeletal and connective tissue disorders
Arthralgia	41/423 (9.7%)	57	47/416 (11.3%)	59
Back pain	78/423 (18.4%)	127	77/416 (18.5%)	124
Musculoskeletal pain	11/423 (2.6%)	15	25/416 (6%)	29
Pain in extremity	28/423 (6.6%)	35	33/416 (7.9%)	45
Nervous system disorders
Headache	57/423 (13.5%)	132	86/416 (20.7%)	160
Multiple sclerosis relapse	17/423 (4%)	35	29/416 (7%)	36
Psychiatric disorders
Depression	35/423 (8.3%)	41	28/416 (6.7%)	35
Respiratory, thoracic and mediastinal disorders
Cough	24/423 (5.7%)	26	35/416 (8.4%)	40
Vascular disorders
Hypertension	32/423 (7.6%)	32	26/416 (6.3%)	26

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.