A Study to Evaluate the Long-term Safety, Tolerability and Effect of Daily Oral Laquinimod 0.6 mg on Disease Course in Subjects With Relapsing Multiple Sclerosis

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01047319
• Collaborator: (none)
• Enrollment: 1,047
• Locations: 144
• Arm: 1
• Actual Duration (Months): 85.1
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To make laquinimod 0.6 mg available for all subjects who completed the placebo-controlled MS-LAQ-302 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: 1047 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-302 (BRAVO) Study, 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
• Actual Study Start Date: May 27, 2010
• Actual Primary Completion Date: Jun 30, 2017
• Actual Study Completion Date: Jun 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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 7.13 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 [Baseline (Day 0 for extension), Day 1 up to 7.13 years]

   Vital signs with potentially clinically significant abnormal results were evaluated using the following significance criteria: Pulse rate: >=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 Note that the change is compared to baseline,

2. Participants With Serum Chemistry Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study [Baseline (Day 0), Day 1 to 7.13 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 [Baseline (Day 0), Day 1 to 7.13 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 [Baseline (Day 0), Day 1 to 7.13 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: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects must have completed the Termination visit of MS-LAQ-302 (completion of all Termination visit activities) according to the MS-LAQ-302 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-302E study.

Exclusion Criteria:

1. Premature discontinuation from the MS-LAQ-302 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-302 study, which preclude safe participation and completion of the MS-LAQ-302E study. Acute exacerbation of MS will not exclude participation in the MS-LAQ-302E 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 1267	Homewood	Alabama	United States	35209
2	Teva Investigational Site 1237	Phoenix	Arizona	United States	85013
3	Teva Investigational Site 1279	Phoenix	Arizona	United States	85018
4	Teva Investigational Site 1276	Tucson	Arizona	United States	85704
5	Teva Investigational Site 1272	Pasadena	California	United States	91105
6	Teva Investigational Site 1238	Sacramento	California	United States	95817
7	Teva Investigational Site 1280	Aurora	Colorado	United States	80045
8	Teva Investigational Site 1282	Sarasota	Florida	United States	34233
9	Teva Investigational Site 1275	Atlanta	Georgia	United States	30309
10	Teva Investigational Site 1250	Peoria	Illinois	United States	61603
11	Teva Investigational Site 1260	Indianapolis	Indiana	United States	46202
12	Teva Investigational Site 1263	Shreveport	Louisiana	United States	71103
13	Teva Investigational Site 1269	Baltimore	Maryland	United States	21201
14	Teva Investigational Site 1273	Albany	New York	United States	12205
15	Teva Investigational Site 1264	Amherst	New York	United States	14226
16	Teva Investigational Site 1261	Akron	Ohio	United States	44320
17	Teva Investigational Site 1245	Cleveland	Ohio	United States	44195-5244
18	Teva Investigational Site 1247	Columbus	Ohio	United States	43221
19	Teva Investigational Site 1244	Portland	Oregon	United States	97225
20	Teva Investigational Site 1281	Nashville	Tennessee	United States	37205
21	Teva Investigational Site 1270	Roanoke	Virginia	United States	24018
22	Teva Investigational Site 1253	Tacoma	Washington	United States	98405
23	Teva Investigational Site 5914	Pleven		Bulgaria	5800
24	Teva Investigational Site 5915	Pleven		Bulgaria	5800
25	Teva Investigational Site 5917	Plovdiv		Bulgaria	4000
26	Teva Investigational Site 4212	Ruse		Bulgaria	7000
27	Teva Investigational Site 5916	Shumen		Bulgaria	9700
28	Teva Investigational Site 5920	Sofia		Bulgaria	1000
29	Teva Investigational Site 5907	Sofia		Bulgaria	1113
30	Teva Investigational Site 5910	Sofia		Bulgaria	1113
31	Teva Investigational Site 5909	Sofia		Bulgaria	1309
32	Teva Investigational Site 5919	Sofia		Bulgaria	1407
33	Teva Investigational Site 5906	Sofia		Bulgaria	1606
34	Teva Investigational Site 5908	Sofia		Bulgaria	1606
35	Teva Investigational Site 5911	Sofia		Bulgaria	1606
36	Teva Investigational Site 5912	Sofia		Bulgaria	1606
37	Teva Investigational Site 5918	Stara Zagora		Bulgaria	6000
38	Teva Investigational Site 5913	Varna		Bulgaria	9010
39	Teva Investigational Site 4211	Veliko Tarnovo		Bulgaria	5000
40	Teva Investigational Site 6003	Osijek		Croatia	31 000
41	Teva Investigational Site 6005	Varazdin		Croatia	42000
42	Teva Investigational Site 6001	Zagreb		Croatia	10000
43	Teva Investigational Site 6002	Zagreb		Croatia	10000
44	Teva Investigational Site 6006	Zagreb		Croatia	10000
45	Teva Investigational Site 5419	Olomouc		Czechia	779 00
46	Teva Investigational Site 5418	Praha 2		Czechia	128 08
47	Teva Investigational Site 5420	Praha 5- Motol		Czechia	150 06
48	Teva Investigational Site 5421	Teplice		Czechia	415 29
49	Teva Investigational Site 5508	Kohtla-Jarve		Estonia	31025
50	Teva Investigational Site 5507	Tallinn		Estonia	EE-10617
51	Teva Investigational Site 5509	Tartu		Estonia	EE-51014
52	Teva Investigational Site 8102	Tbilisi		Georgia	0112
53	Teva Investigational Site 8104	Tbilisi		Georgia	0112
54	Teva Investigational Site 8103	Tbilisi		Georgia	0179
55	Teva Investigational Site 6703	Berlin		Germany	10117
56	Teva Investigational Site 6402	Berlin		Germany	12203
57	Teva Investigational Site 6400	Ulm		Germany	89081
58	Teva Investigational Site 8041	Jerusalem		Israel	9112001
59	Teva Investigational Site 8040	Ramat Gan		Israel	5262160
60	Teva Investigational Site 3056	Bologna		Italy	40139
61	Teva Investigational Site 3053	Cefalu		Italy	90015
62	Teva Investigational Site 3054	Chieti		Italy	66100
63	Teva Investigational Site 3061	Empoli		Italy	50053
64	Teva Investigational Site 3049	Firenze		Italy	50139
65	Teva Investigational Site 3055	Napoli		Italy	80131
66	Teva Investigational Site 3048	Rome		Italy	00133
67	Teva Investigational Site 3052	Rome		Italy	00149
68	Teva Investigational Site 3050	Rome		Italy	00168
69	Teva Investigational Site 5708	Kaunas		Lithuania	50009
70	Teva Investigational Site 5707	Siauliai		Lithuania	76231
71	Teva Investigational Site 6500	Skopje		North Macedonia	1000
72	Teva Investigational Site 6501	Skopje		North Macedonia	1000
73	Teva Investigational Site 6502	Skopje		North Macedonia	1000
74	Teva Investigational Site 5337	Bialystok		Poland	15-402
75	Teva Investigational Site 5329	Gdansk		Poland	80-803
76	Teva Investigational Site 5338	Gdansk		Poland	80-952
77	Teva Investigational Site 6602	Gorzow Wielkopolski		Poland	66-400
78	Teva Investigational Site 5333	Grodzisk Mazowiecki		Poland	05-825
79	Teva Investigational Site 5334	Katowice		Poland	40-650
80	Teva Investigational Site 5339	Katowice		Poland	40-684
81	Teva Investigational Site 6603	Kielce		Poland	25-726
82	Teva Investigational Site 4213	Konskie		Poland	26-200
83	Teva Investigational Site 5332	Koscierzyna		Poland	83-400
84	Teva Investigational Site 5345	Krakow		Poland	31-826
85	Teva Investigational Site 5328	Lodz		Poland	90-153
86	Teva Investigational Site 5330	Olsztyn		Poland	10-560
87	Teva Investigational Site 5331	Szczecin		Poland	70-111
88	Teva Investigational Site 5336	Warsaw		Poland	02-957
89	Teva Investigational Site 5340	Warszawa		Poland	00-909
90	Teva Investigational Site 5341	Warszawa		Poland	02-097
91	Teva Investigational Site 5335	Wroclaw		Poland	50-556
92	Teva Investigational Site 5235	Balotesti		Romania	077015
93	Teva Investigational Site 5218	Bucharest		Romania	010825
94	Teva Investigational Site 5214	Bucuresti		Romania	022328
95	Teva Investigational Site 5213	Bucuresti		Romania	050098
96	Teva Investigational Site 5215	Cluj-Napoca		Romania	400012
97	Teva Investigational Site 5217	Constanta		Romania	900591
98	Teva Investigational Site 8209	Craiova		Romania	200515
99	Teva Investigational Site 5216	Iasi		Romania	700661
100	Teva Investigational Site 5219	Sibiu		Romania	550245
101	Teva Investigational Site 5043	Barnaul		Russian Federation	656024
102	Teva Investigational Site 5033	Moscow		Russian Federation	117152
103	Teva Investigational Site 5041	Moscow		Russian Federation	125367
104	Teva Investigational Site 5032	Moscow		Russian Federation	127015
105	Teva Investigational Site 5038	Novosibirsk		Russian Federation	630087
106	Teva Investigational Site 5042	Novosibirsk		Russian Federation	630117
107	Teva Investigational Site 5035	Saint Petersburg		Russian Federation	197022
108	Teva Investigational Site 5037	Samara		Russian Federation	443095
109	Teva Investigational Site 5036	St. Petersburg		Russian Federation	194291
110	Teva Investigational Site 5034	St. Petersburg		Russian Federation	197376
111	Teva Investigational Site 5044	Ufa		Russian Federation	450007
112	Teva Investigational Site 6200	Bratislava		Slovakia	813 69
113	Teva Investigational Site 6201	Bratislava		Slovakia	826 06
114	Teva Investigational Site 6202	Nitra		Slovakia	949 01
115	Teva Investigational Site 6203	Zilina		Slovakia	010 01
116	Teva Investigational Site 9007	Bloemfontein		South Africa	9301
117	Teva Investigational Site 9001	Cape Town		South Africa	7925
118	Teva Investigational Site 9004	Johannesburg		South Africa	2157
119	Teva Investigational Site 9003	Parktown- Johannesburg		South Africa	2193
120	Teva Investigational Site 9008	Pietermaritzburg		South Africa	3201
121	Teva Investigational Site 9005	Pretoria		South Africa	0041
122	Teva Investigational Site 9006	Rosebank		South Africa	2196
123	Teva Investigational Site 3147	Barcelona		Spain	08035
124	Teva Investigational Site 3154	Figueres-Girona		Spain	17600
125	Teva Investigational Site 3149	L'Hospitalet de Llobregat		Spain	08907
126	Teva Investigational Site 3152	Madrid		Spain	28041
127	Teva Investigational Site 3151	Malaga		Spain	29010
128	Teva Investigational Site 3148	Sevilla		Spain	41009
129	Teva Investigational Site 3153	Tortosa-Tarragona		Spain	43500
130	Teva Investigational Site 6503	Chernihiv		Ukraine	14029
131	Teva Investigational Site 5823	Chernivtsi		Ukraine	58018
132	Teva Investigational Site 5811	Dnipropetrovsk		Ukraine	49027
133	Teva Investigational Site 5812	Donetsk		Ukraine	83003
134	Teva Investigational Site 5814	Ivano-Frankivsk		Ukraine	76008
135	Teva Investigational Site 5817	Kharkiv		Ukraine	61018
136	Teva Investigational Site 5818	Kharkiv		Ukraine	61068
137	Teva Investigational Site 5815	Kharkiv		Ukraine	61103
138	Teva Investigational Site 5822	Kyiv		Ukraine	03110
139	Teva Investigational Site 5809	Lviv		Ukraine	79010
140	Teva Investigational Site 5820	Odessa		Ukraine	65025
141	Teva Investigational Site 5821	Poltava		Ukraine	36024
142	Teva Investigational Site 5810	Vinnytsya		Ukraine	21005
143	Teva Investigational Site 5819	Zaporizhzhya		Ukraine	69035
144	Teva Investigational Site 5816	Zaporizhzhya		Ukraine	69600

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Principal Investigator: Prof. Timothy Vollmer, MD, University of Colorado, Denver

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: NCT01047319
• Other Study ID Numbers: MS-LAQ-302E; 2009-015815-42
• First Posted: Jan 12, 2010
• 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	All participants who completed the full duration of the double-blind BRAVO study (study MS-LAQ-302) were eligible to enter into Study MS-LAQ-302E. Of the 1090 participants who completed MS-LAQ-302, 1047 opted to continue into the open-label extension study.
Pre-assignment Detail	1047 subjects with RRMS were enrolled to receive laquinimod 0.6 mg daily at 144 study sites in 18 countries by 144 investigators.

Arm/Group Title	Early Laquinimod	Switch From Placebo	Switch From Avonex
Arm/Group Description	All participants in MS-LAQ-302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-302E 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-302 double-blind study who were administered placebo daily for 24 months.	All participants in MS-LAQ-302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.
Period Title: Overall Study
STARTED	345	350	352
COMPLETED	0	0	0
NOT COMPLETED	345	350	352

Baseline Characteristics

Arm/Group Title	Early Laquinimod	Switch From Placebo	Switch From Avonex	Total
Arm/Group Description	All participants in MS-LAQ-302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-302E 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-302 double-blind study who were administered placebo daily for 24 months.	All participants in MS-LAQ-302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.	Total of all reporting groups
Overall Participants	345	350	352	1047
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.2 (9.16)	40.1 (9.23)	40.1 (9.34)	39.8 (9.24)
Sex: Female, Male (Count of Participants)
Female	228 66.1%	245 70%	234 66.5%	707 67.5%
Male	117 33.9%	105 30%	118 33.5%	340 32.5%
Race/Ethnicity, Customized (Count of Participants)
Asian/Oriental	1 0.3%	0 0%	1 0.3%	2 0.2%
Black/African American	2 0.6%	2 0.6%	2 0.6%	6 0.6%
White	338 98%	346 98.9%	348 98.9%	1032 98.6%
Unknown	2 0.6%	2 0.6%	0 0%	4 0.4%
Other	2 0.6%	0 0%	1 0.3%	3 0.3%

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 7.13 years

Outcome Measure Data

Analysis Population Description

Safety

Arm/Group Title	Early Laquinimod	Switch From Placebo	Switch From Avonex
Arm/Group Description	All participants in MS-LAQ-302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-302E 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-302 double-blind study who were administered placebo daily for 24 months.	All participants in MS-LAQ-302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.
Measure Participants	345	350	352
=>1 TEAE	290 84.1%	303 86.6%	279 79.3%
=>1 Serious TEAE	54 15.7%	65 18.6%	51 14.5%
=>1 Severe TEAE	36 10.4%	54 15.4%	44 12.5%
=>1 TEAE causing discontinuation	20 5.8%	28 8%	23 6.5%
=>1 TEAE of special interest	66 19.1%	64 18.3%	73 20.7%
=>1 treatment-related TEAE	66 19.1%	76 21.7%	96 27.3%
=>1 TEAE leading to death	5 1.4%	3 0.9%	5 1.4%

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: >=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 Note that the change is compared to baseline,
Time Frame	Baseline (Day 0 for extension), Day 1 up to 7.13 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	Switch From Avonex
Arm/Group Description	All participants in MS-LAQ-302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-302E 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-302 double-blind study who were administered placebo daily for 24 months.	All participants in MS-LAQ-302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.
Measure Participants	345	350	352
Participants with at least one abnormality	19 5.5%	23 6.6%	19 5.4%
Pulse rate - high	2 0.6%	0 0%	0 0%
Systolic blood pressure - low	4 1.2%	7 2%	9 2.6%
Systolic blood pressure - high	0 0%	2 0.6%	0 0%
Diastolic blood pressure - low	4 1.2%	5 1.4%	4 1.1%
Diastolic blood pressure - high	9 2.6%	10 2.9%	7 2%

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	Baseline (Day 0), Day 1 to 7.13 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	Switch From Avonex
Arm/Group Description	All participants in MS-LAQ-302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-302E 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-302 double-blind study who were administered placebo daily for 24 months.	All participants in MS-LAQ-302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.
Measure Participants	344	349	347
ALT - change from Low / Non-PCS to High PCS	5 1.4%	8 2.3%	10 2.8%
Albumen - change from High / Non-PCS to Low PCS	0 0%	1 0.3%	0 0%
ALP - change from Low / Non-PCS to High PCS	0 0%	2 0.6%	0 0%
p-Amylase - change from Low / Non-PCS to High PCS	5 1.4%	1 0.3%	2 0.6%
AST - change from Low / Non-PCS to High PCS	3 0.9%	2 0.6%	5 1.4%
Bilirubin - change from Low / Non-PCS to High PCS	2 0.6%	3 0.9%	2 0.6%
CRP - change from Low / Non-PCS to High PCS	36 10.4%	32 9.1%	31 8.8%
Calcium - change from High / Non-PCS to Low PCS	1 0.3%	1 0.3%	1 0.3%
Calcium - change from Low / Non-PCS to High PCS	1 0.3%	1 0.3%	2 0.6%
CK - change from Low / Non-PCS to High PCS	11 3.2%	12 3.4%	10 2.8%
CTN - change from Low / Non-PCS to High PCS	1 0.3%	1 0.3%	0 0%
FIB - change from Low / Non-PCS to High PCS	22 6.4%	24 6.9%	25 7.1%
GGT - change from Low / Non-PCS to High PCS	16 4.6%	22 6.3%	18 5.1%
Glucose - change from High / Non-PCS to Low PCS	12 3.5%	16 4.6%	11 3.1%
Glucose - change from Low / Non-PCS to High PCS	4 1.2%	5 1.4%	2 0.6%
Phosphate-change from High / Non-PCS to Low PCS	12 3.5%	12 3.4%	6 1.7%
Phosphate-change from Low / Non-PCS to High PCS	17 4.9%	18 5.1%	16 4.5%
K - change from High / Non-PCS to Low PCS	2 0.6%	4 1.1%	2 0.6%
K - change from Low / Non-PCS to High PCS	46 13.3%	39 11.1%	38 10.8%
Sodium - change from High / Non-PCS to Low PCS	4 1.2%	2 0.6%	3 0.9%
Sodium - change from Low / Non-PCS to High PCS	21 6.1%	16 4.6%	17 4.8%
Urea - change from Low / Non-PCS to High PCS	4 1.2%	4 1.1%	3 0.9%

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	Baseline (Day 0), Day 1 to 7.13 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	Switch From Avonex
Arm/Group Description	All participants in MS-LAQ-302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-302E 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-302 double-blind study who were administered placebo daily for 24 months.	All participants in MS-LAQ-302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.
Measure Participants	344	349	347
Hematocrit - change from High / Non-PCS to Low PCS	30 8.7%	25 7.1%	21 6%
Hemoglobin -change from High / Non-PCS to Low PCS	21 6.1%	24 6.9%	15 4.3%
Leukocytes - change from High / Non-PCS to Low PCS	2 0.6%	4 1.1%	2 0.6%
Leukocytes - change from Low / Non-PCS to High PCS	4 1.2%	1 0.3%	5 1.4%
Neutrophils - change from High/Non-PCS to Low PCS	25 7.2%	12 3.4%	14 4%
Platelets - change from High / Non-PCS to Low PCS	5 1.4%	3 0.9%	2 0.6%
Platelets - change from Low / Non-PCS to High PCS	4 1.2%	4 1.1%	4 1.1%

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	Baseline (Day 0), Day 1 to 7.13 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	Switch From Avonex
Arm/Group Description	All participants in MS-LAQ-302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.	All participants in MS-LAQ-302E 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-302 double-blind study who were administered placebo daily for 24 months.	All participants in MS-LAQ-302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.
Measure Participants	340	346	345
Normal / Normal	150 43.5%	148 42.3%	134 38.1%
Normal / Abnormal, Not CS	109 31.6%	125 35.7%	119 33.8%
Normal / Abnormal, CS	5 1.4%	3 0.9%	5 1.4%
Abnormal, Not CS / Normal	5 1.4%	7 2%	20 5.7%
Abnormal, Not CS / Abnormal, Not CS	67 19.4%	62 17.7%	64 18.2%
Abnormal, Not CS / Abnormal, CS	4 1.2%	0 0%	2 0.6%
Abnormal, CS / Normal	0 0%	0 0%	0 0%
Abnormal, CS / Abnormal, Not CS	0 0%	0 0%	1 0.3%
Abnormal, CS / Abnormal, CS	0 0%	1 0.3%	0 0%

Adverse Events

Time Frame	Day 1 up to 7.13 years
Arm/Group Title	Early Laquinimod		Switch From Placebo		Switch From Avonex
Arm/Group Description	All participants in MS-LAQ- 302E 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-302 double-blind study who were administered laquinimod 0.6 mg daily for 24 months.		All participants in MS-LAQ- 302E 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-302 double-blind study who were administered placebo daily for 24 months.		All participants in MS-LAQ- 302E 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 Avonex subgroup included participants in MS-LAQ-302 rater-blind study who were administered Avonex 30 mcg IM once weekly for 24 months.
All Cause Mortality
	Early Laquinimod		Switch From Placebo		Switch From Avonex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/345 (1.4%)		3/350 (0.9%)		5/352 (1.4%)
Serious Adverse Events
	Early Laquinimod		Switch From Placebo		Switch From Avonex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/345 (15.7%)		65/350 (18.6%)		51/352 (14.5%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Thrombocytopenia	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cardiac disorders
Acute left ventricular failure	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Acute myocardial infarction	2/345 (0.6%)	2	0/350 (0%)	0	2/352 (0.6%)	2
Arrhythmia	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Atrial flutter	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cardiac failure	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Cardiac failure acute	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Cardiac failure congestive	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Cardiopulmonary failure	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cardiovascular insufficiency	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Coronary artery dissection	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Coronary artery stenosis	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Left ventricular failure	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Myocardial infarction	0/345 (0%)	0	0/350 (0%)	0	3/352 (0.9%)	3
Stress cardiomyopathy	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Supraventricular tachycardia	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Ventricular extrasystoles	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Ventricular fibrillation	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Congenital, familial and genetic disorders
Hydrocele	1/345 (0.3%)	1	1/350 (0.3%)	1	0/352 (0%)	0
Ear and labyrinth disorders
Vertigo	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Endocrine disorders
Adrenal mass	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Goitre	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Hyperthyroidism	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Eye disorders
Blepharitis	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Cataract nuclear	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Iridocyclitis	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Ocular hypertension	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Gastrointestinal disorders
Abdominal hernia	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Abdominal pain	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Anal fissure	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Faecaloma	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Inflammatory bowel disease	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Inguinal hernia	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Irritable bowel syndrome	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	2
Large intestinal obstruction	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Large intestine perforation	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Pancreatitis	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Pancreatitis acute	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Pancreatitis chronic	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Proctitis	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Vomiting	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
General disorders
Pyrexia	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Hepatobiliary disorders
Cholangitis	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cholecystitis	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Cholecystitis chronic	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Cholelithiasis	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Hepatitis toxic	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Immune system disorders
Allergy to metals	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Food allergy	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Infections and infestations
Abdominal wall abscess	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Acute hepatitis C	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Appendicitis	2/345 (0.6%)	2	0/350 (0%)	0	1/352 (0.3%)	1
Bronchitis	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Carbuncle	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Cellulitis	1/345 (0.3%)	1	1/350 (0.3%)	1	0/352 (0%)	0
Chorioretinitis	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cystitis	2/345 (0.6%)	2	0/350 (0%)	0	0/352 (0%)	0
Diverticulitis	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Escherichia sepsis	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
HIV infection	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Herpes zoster	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Incision site abscess	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Infectious pleural effusion	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Lung abscess	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Meningitis viral	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Orchitis	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Papilloma viral infection	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Peritonitis	2/345 (0.6%)	2	1/350 (0.3%)	1	1/352 (0.3%)	1
Pilonidal cyst	0/345 (0%)	0	0/350 (0%)	0	2/352 (0.6%)	2
Pneumonia	1/345 (0.3%)	1	1/350 (0.3%)	1	2/352 (0.6%)	2
Pulmonary tuberculosis	1/345 (0.3%)	1	1/350 (0.3%)	1	2/352 (0.6%)	2
Pyelonephritis	1/345 (0.3%)	1	1/350 (0.3%)	1	0/352 (0%)	0
Salpingo-oophoritis	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Tuberculosis	0/345 (0%)	0	0/350 (0%)	0	2/352 (0.6%)	2
Urinary tract infection	3/345 (0.9%)	3	1/350 (0.3%)	1	2/352 (0.6%)	2
Viral pharyngitis	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Viral upper respiratory tract infection	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Wound infection staphylococcal	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Injury, poisoning and procedural complications
Accident	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Animal bite	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Ankle fracture	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Cervical vertebral fracture	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Concussion	1/345 (0.3%)	1	1/350 (0.3%)	1	0/352 (0%)	0
Contusion	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Craniocerebral injury	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Epiphyseal fracture	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Facial bones fracture	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Fall	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Femur fracture	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Humerus fracture	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Joint dislocation	0/345 (0%)	0	2/350 (0.6%)	2	0/352 (0%)	0
Ligament sprain	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Meniscus injury	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Pneumothorax traumatic	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Radius fracture	0/345 (0%)	0	2/350 (0.6%)	2	0/352 (0%)	0
Road traffic accident	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Skeletal injury	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Splenic rupture	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Subdural haematoma	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Tibia fracture	1/345 (0.3%)	1	1/350 (0.3%)	1	0/352 (0%)	0
Ulna fracture	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Upper limb fracture	1/345 (0.3%)	1	1/350 (0.3%)	1	0/352 (0%)	0
Ureteric injury	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Wound	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Investigations
Hepatic enzyme increased	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Metabolism and nutrition disorders
Lactose intolerance	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/345 (0.6%)	2	1/350 (0.3%)	1	0/352 (0%)	0
Bursitis	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Intervertebral disc protrusion	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Jaw cyst	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Myalgia	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Osteoarthritis	2/345 (0.6%)	2	2/350 (0.6%)	2	0/352 (0%)	0
Pain in extremity	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Spinal osteoarthritis	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Adenocarcinoma	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Adenocarcinoma of colon	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Basal cell carcinoma	1/345 (0.3%)	1	1/350 (0.3%)	1	0/352 (0%)	0
Breast cancer	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Breast cancer stage II	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cervix carcinoma stage II	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Fibrous histiocytoma	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Intraductal proliferative breast lesion	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Invasive ductal breast carcinoma	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Keratoacanthoma	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Malignant melanoma	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Malignant melanoma in situ	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Malignant neoplasm of renal pelvis	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Metastases to liver	0/345 (0%)	0	2/350 (0.6%)	2	0/352 (0%)	0
Neuroma	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Non-small cell lung cancer metastatic	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Papillary thyroid cancer	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Rectal adenocarcinoma	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Rectal cancer	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Squamous cell carcinoma of the cervix	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Uterine cancer	0/345 (0%)	0	2/350 (0.6%)	2	0/352 (0%)	0
Uterine leiomyoma	3/345 (0.9%)	4	4/350 (1.1%)	4	3/352 (0.9%)	3
Nervous system disorders
Altered state of consciousness	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Brain oedema	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cerebral haemorrhage	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Dizziness	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Epilepsy	1/345 (0.3%)	1	1/350 (0.3%)	2	1/352 (0.3%)	1
Hemiparesis	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Hypoaesthesia	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Ischaemic stroke	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Lumbar radiculopathy	0/345 (0%)	0	2/350 (0.6%)	2	0/352 (0%)	0
Multiple sclerosis relapse	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Muscle spasticity	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Radiculopathy	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Sciatica	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Thrombotic stroke	0/345 (0%)	0	1/350 (0.3%)	2	0/352 (0%)	0
Trigeminal neuralgia	0/345 (0%)	0	3/350 (0.9%)	3	1/352 (0.3%)	1
Pregnancy, puerperium and perinatal conditions
Abortion missed	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Abortion spontaneous	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Product Issues
Device loosening	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Psychiatric disorders
Alcohol withdrawal syndrome	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Completed suicide	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Depression	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Disorientation	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Mood disorder due to a general medical condition	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Panic attack	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Renal and urinary disorders
Calculus urinary	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Crush syndrome	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Hydronephrosis	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Hypertonic bladder	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Micturition disorder	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Nephrolithiasis	0/345 (0%)	0	1/350 (0.3%)	4	1/352 (0.3%)	1
Ureterolithiasis	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Urinary incontinence	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Reproductive system and breast disorders
Bartholin's cyst	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Cervical dysplasia	0/345 (0%)	0	3/350 (0.9%)	3	0/352 (0%)	0
Cervical polyp	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Cervix disorder	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Endometriosis	0/345 (0%)	0	4/350 (1.1%)	5	0/352 (0%)	0
Menorrhagia	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Menstrual disorder	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Metrorrhagia	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Ovarian cyst ruptured	0/345 (0%)	0	2/350 (0.6%)	2	0/352 (0%)	0
Ovarian haemorrhage	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Pelvic adhesions	1/345 (0.3%)	2	0/350 (0%)	0	0/352 (0%)	0
Postmenopausal haemorrhage	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Uterine polyp	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Vaginal cyst	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/345 (0%)	0	1/350 (0.3%)	1	1/352 (0.3%)	1
Chronic respiratory failure	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Paranasal cyst	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Pleural effusion	1/345 (0.3%)	1	0/350 (0%)	0	1/352 (0.3%)	1
Pleurisy	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Pulmonary oedema	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Surgical and medical procedures
Bartholin's cyst removal	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Cholecystectomy	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Fracture reduction	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Hysterectomy	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Inguinal hernia repair	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Osteosynthesis	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Radical hysterectomy	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Skin lesion excision	1/345 (0.3%)	1	0/350 (0%)	0	0/352 (0%)	0
Splenectomy	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Thyroidectomy	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Vascular disorders
Aortic rupture	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Circulatory collapse	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Deep vein thrombosis	0/345 (0%)	0	1/350 (0.3%)	1	2/352 (0.6%)	2
Hypovolaemic shock	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Internal haemorrhage	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Jugular vein thrombosis	0/345 (0%)	0	1/350 (0.3%)	1	0/352 (0%)	0
Thrombophlebitis superficial	0/345 (0%)	0	0/350 (0%)	0	1/352 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Early Laquinimod		Switch From Placebo		Switch From Avonex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	215/345 (62.3%)		205/350 (58.6%)		194/352 (55.1%)
Blood and lymphatic system disorders
Anaemia	22/345 (6.4%)	34	20/350 (5.7%)	24	15/352 (4.3%)	18
Infections and infestations
Bronchitis	24/345 (7%)	26	23/350 (6.6%)	29	16/352 (4.5%)	27
Influenza	27/345 (7.8%)	34	25/350 (7.1%)	38	22/352 (6.3%)	32
Nasopharyngitis	52/345 (15.1%)	96	46/350 (13.1%)	77	37/352 (10.5%)	58
Pharyngitis	11/345 (3.2%)	18	18/350 (5.1%)	24	11/352 (3.1%)	15
Respiratory tract infection viral	20/345 (5.8%)	25	15/350 (4.3%)	24	16/352 (4.5%)	20
Upper respiratory tract infection	36/345 (10.4%)	62	36/350 (10.3%)	63	28/352 (8%)	59
Urinary tract infection	22/345 (6.4%)	30	18/350 (5.1%)	22	17/352 (4.8%)	22
Investigations
C-reactive protein increased	19/345 (5.5%)	25	17/350 (4.9%)	23	14/352 (4%)	16
Weight increased	19/345 (5.5%)	23	11/350 (3.1%)	11	9/352 (2.6%)	10
Musculoskeletal and connective tissue disorders
Arthralgia	21/345 (6.1%)	27	23/350 (6.6%)	27	28/352 (8%)	38
Back pain	49/345 (14.2%)	74	49/350 (14%)	72	50/352 (14.2%)	73
Nervous system disorders
Headache	44/345 (12.8%)	84	60/350 (17.1%)	121	74/352 (21%)	128
Psychiatric disorders
Depression	26/345 (7.5%)	26	20/350 (5.7%)	21	17/352 (4.8%)	21
Vascular disorders
Hypertension	18/345 (5.2%)	22	21/350 (6%)	23	18/352 (5.1%)	18

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.