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CONCERTO: The Efficacy, Safety, and Tolerability of Laquinimod in Participants With Relapsing Remitting Multiple Sclerosis (RRMS)

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01707992
Collaborator
(none)
2,199
Enrollment
284
Locations
6
Arms
52.4
Actual Duration (Months)
7.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study followed by active treatment, to evaluate the efficacy, safety and tolerability of two doses of oral administration of laquinimod in participants with RRMS. The study has 2 periods: Period 1, the double-blind, placebo-controlled period (up to 24 months) and Period 2, the active treatment period (24 months).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
2199 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Followed by an Active Treatment Period, to Evaluate the Efficacy, Safety and Tolerability of Two Doses of Oral Administration of Laquinimod (0.6 mg/Day or 1.2 mg/Day) in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)
Actual Study Start Date :
Feb 20, 2013
Actual Primary Completion Date :
Apr 13, 2015
Actual Study Completion Date :
Jul 4, 2017

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo-Controlled Phase: Placebo

Participants will receive 2 capsules of placebo (matching to laquinimod 0.6 milligrams [mg]) once daily orally for up to 24 months.

Drug: Placebo
Placebo matching to laquinimod will be administered as per the schedule specified in the respective arms.
Experimental: Placebo-Controlled Phase: Laquinimod 0.6 mg

Participants will receive 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months.

Drug: Laquinimod
Laquinimod will be administered as per the dose and schedule specified in the respective arms.

Drug: Placebo
Placebo matching to laquinimod will be administered as per the schedule specified in the respective arms.
Experimental: Placebo-Controlled Phase: Laquinimod 1.2 mg

Participants will receive laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.

Drug: Laquinimod
Laquinimod will be administered as per the dose and schedule specified in the respective arms.
Experimental: Active Treatment Phase: Laquinimod 0.6 mg

Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, will receive 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months.

Drug: Laquinimod
Laquinimod will be administered as per the dose and schedule specified in the respective arms.

Drug: Placebo
Placebo matching to laquinimod will be administered as per the schedule specified in the respective arms.
Experimental: Active Treatment Phase: Laquinimod 1.2 mg

Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, will receive laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.

Drug: Laquinimod
Laquinimod will be administered as per the dose and schedule specified in the respective arms.
No Intervention: Active Treatment Phase: Off Drug

Participants who were discontinued from treatment with laquinimod 1.2 mg during the placebo-controlled phase due to sponsor decision after 01 January 2016 will continue the active-treatment phase off drug for 24 months.

Outcome Measures

Primary Outcome Measures

  1. Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months) [Baseline to Month 24]

    Time to CDP was defined as the time to a sustained increase in Kurtzke's Expanded Disability Status Scale (EDSS) score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least three months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]). Data is presented as distribution of CDP (number of participants with CDP) sustained for 3 months.

Secondary Outcome Measures

  1. Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15 [Baseline, Month 15]

    Brain atrophy was defined by the percent change in brain volume from baseline to Month 15. For participants who prematurely discontinued treatment or completed the placebo-controlled phase before Month 15, the last available measurement was used, provided it was performed at least 9 months following the initiation of study drug.

  2. Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse) [Baseline to Month 24]

    Relapse was defined as appearance of one or more new neurological abnormalities or reappearance or worsening of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in absence of fever or any infection) and immediately preceded by an improving neurological state of at least 30 days from onset of previous relapse. An event was counted as a relapse only when the participant's symptoms were accompanied by observed objective neurological changes, consistent with an increase of at least 0.5 in EDSS; or one grade in score of 2 or more of 7 Functional Systems (FS) (excluding changes in bowel or bladder function or cognition); or 2 grades in score of one of the FS as compared to previous evaluation. EDSS assesses disability in 8 FS with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of relapsing participants (number of participants with confirmed relapse).

  3. Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months) [Baseline to Month 24]

    Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 6 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 6 months.

  4. Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months) [Baseline to Month 24]

    Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 9 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 9 months.

Other Outcome Measures

  1. Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs) [Baseline up to Month 24]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.

  2. Active-Treatment Phase: Number of Participants With AEs [Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.

  3. Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities [Baseline up to Week 24]

    Clinically significant vital signs abnormalities included: Pulse rate: greater than or equal to (>=) 120 beats per minute (bpm) and increase from baseline of >=30 bpm, <=45 bpm and decrease from baseline of >=30 bpm; Systolic blood pressure: >=180 millimeters of mercury (mmHg) and increase from baseline of >=30 mmHg, <=90 and decrease from baseline of >=30 mmHg; Diastolic blood pressure: >=100 mmHg and increase from baseline of >=20 mmHg, <=50 mmHg and decrease from baseline of >=20 mmHg.

  4. Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities [Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase]

    Clinically significant vital signs abnormalities included: Pulse rate: >=120 bpm and increase from baseline of >=30 bpm, <=45 bpm and decrease from baseline of >=30 bpm; Systolic blood pressure: >=180 mmHg and increase from baseline of >=30 mmHg, <=90 and decrease from baseline of >=30 mmHg; Diastolic blood pressure: >=100 mmHg and increase from baseline of >=20 mmHg, <=50 mmHg and decrease from baseline of >=20 mmHg.

  5. Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters [Baseline, Endpoint (Month 24)]

    ECG parameters included: PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.

  6. Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters [Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase), endpoint (Month 24 of active-treatment phase)]

    ECG parameters included: PR interval, QRS interval, QTcF and QTcB. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.

  7. Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry [Baseline up to Month 24]

    Potentially clinically significant serum chemistry abnormalities included: Glucose <=3 and >=13.88 millimoles per liter (mmol/L); Alanine aminotransferase (ALT) (in units per liter [U/L]), aspartate aminotransferase (AST) (in U/L), alkaline phosphatase (in U/L), gamma-glutamyltransferase (GGT) (in U/L), creatine phosphokinase (CPK) (in U/L), C-reactive protein (CRP) (in milligrams per liter [mg/L]), pancreatic amylase (in U/L)>=3 * upper limit of normal (ULN); Fibrinogen >=6 grams per liter (gm/L); Sodium <=130 and >=150 mmol/L; Potassium <=3.2 and >=5.5 mmol/L; Calcium <=1.87 and >=2.75 mmol/L; Phosphate <=0.65 and >=1.61 mmol/L.

  8. Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry [Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase]

    Potentially clinically significant serum chemistry abnormalities included: Glucose <=3 and >=13.88 mmol/L; ALT (in U/L), AST (in U/L), alkaline phosphatase (in U/L), GGT (in U/L), CPK (in U/L), CRP (in mg/L), pancreatic amylase (in U/L)>=3 * ULN; Fibrinogen >=6 gm/L; Sodium <=130 and >=150 mmol/L; Potassium <=3.2 and >=5.5 mmol/L; Calcium <=1.87 and >=2.75 mmol/L; Phosphate <=0.65 and >=1.61 mmol/L; Blood urea nitrogen (in mmol/L); Total bilirubin >=28 micromols per liter (micromols/L); Creatinine >=117 micromols/L; Albumin <=25 gm/L.

  9. Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values [Baseline up to Month 24]

    Potentially clinically significant hematological abnormalities included: Hemoglobin <=11.5 grams per deciliter (gm/dL) in males and <=10 gm/dL in females; White blood cells (WBCs) count <=2.5 and >=21*10^9 per liter (L); Absolute neutrophil count (ANC) <=1.49*10^9 per L; Platelet count <=100 and >=600*10^9 per L.

  10. Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values [Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase]

    Potentially clinically significant hematological abnormalities included: Hemoglobin <=11.5, >=20 gm/dL in males, and <=10, >=18.5 gm/dL in females; WBCs count <=2.5 and >=21*10^9 per L; ANC <=1.49*10^9 per L; Platelet count <=100 and >=600*10^9 per L.

Eligibility Criteria

Criteria

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

  • Participants must have a confirmed and documented multiple sclerosis (MS) diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course.

  • Participants must be ambulatory with Kurtzke's expanded disability status scale (EDSS) score of 0 to 5.5 in both screening and randomization visits.

  • Participants must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or per os (PO)/oral] or adrenocorticotrophic hormone, 60 days prior to randomization.

  • Participants must have experienced at least one documented relapse in the 12 months prior to randomization.

  • Participants must have disease duration of not more than 15 years.

  • Women of child-bearing potential (for example, women who are not postmenopausal or surgically sterilized) must practice an acceptable method of birth control for 30 days before taking the study drug and two acceptable methods of birth control during the duration of the study and until 30 days after the last dose of study medication.

  • Additional criteria apply, please contact the investigator for more information.

Exclusion Criteria:

  • Participants with progressive forms of MS.

  • Participants with neuromyelitis optica.

  • Use of experimental or investigational drugs and/or participation in drug clinical studies within the 6 months prior to randomization.

  • Use of immunosuppressive agents or cytotoxic agents, including cyclophosphamide, within 6 months prior to randomization.

  • Use of either of the following within 2 years prior to randomization visit: natalizumab (Tysabri®), rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab.

  • Use of teriflunomide (Aubagio®) within 2 years prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to randomization.

  • Previous treatment with glatiramer acetate (Copaxone®) Interferon β (either 1a or 1b), fingolimod (Gilenya®), dimethyl fumarate (Tecfidera®) or intravenous immunoglobulins within 2 months prior to randomization.

  • Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to randomization.

  • Previous use of mitoxantrone (Novantrone®), cladribine, or alemtuzumab (Lemtrada®).

  • Previous use of laquinimod.

  • Previous total body irradiation or total lymphoid irradiation.

  • Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.

  • Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to randomization.

  • Use of inducers of CYP3A4 within 2 weeks prior to randomization visit.

  • Pregnancy or breastfeeding.

  • A known history of sensitivity to gadolinium (Gd).

  • Inability to successfully undergo magnetic resonance imaging (MRI) scanning.

  • Participants who underwent endovascular treatment for chronic cerebrospinal venous insufficiency within 3 months prior to randomization.

  • Additional criteria apply, please contact the investigator for more information.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Teva Investigational Site 10329 Cullman Alabama United States 35058
2 Teva Investigational Site 10349 Sun City Arizona United States 85351
3 Teva Investigational Site 10342 Tucson Arizona United States 85741-3537
4 Teva Investigational Site 10310 Fresno California United States 93710
5 Teva Investigational Site 10307 Aurora Colorado United States 80045
6 Teva Investigational Site 10334 Centennial Colorado United States 80112
7 Teva Investigational Site 10332 Fort Collins Colorado United States 80528
8 Teva Investigational Site 10316 Coral Gables Florida United States 33146
9 Teva Investigational Site 10341 Saint Petersburg Florida United States 33701
10 Teva Investigational Site 10308 Sarasota Florida United States 34233
11 Teva Investigational Site 10315 Sunrise Florida United States 33351
12 Teva Investigational Site 10323 Tampa Florida United States 33606
13 Teva Investigational Site 10350 Chicago Illinois United States 60612
14 Teva Investigational Site 10345 Evanston Illinois United States 60201
15 Teva Investigational Site 10343 Northbrook Illinois United States 60062
16 Teva Investigational Site 10339 Fort Wayne Indiana United States 46805
17 Teva Investigational Site 10348 Lenexa Kansas United States 66214
18 Teva Investigational Site 10338 Boston Massachusetts United States 02215
19 Teva Investigational Site 10346 Advance North Carolina United States 27006
20 Teva Investigational Site 10347 Winston-Salem North Carolina United States 27157
21 Teva Investigational Site 10309 Bellevue Ohio United States 44811
22 Teva Investigational Site 10317 Columbus Ohio United States 43221
23 Teva Investigational Site 10325 Dayton Ohio United States 45417
24 Teva Investigational Site 10340 Hershey Pennsylvania United States 17033-0850
25 Teva Investigational Site 10331 Philadelphia Pennsylvania United States 19104
26 Teva Investigational Site 10313 Cordova Tennessee United States 38018
27 Teva Investigational Site 10324 Franklin Tennessee United States 37064
28 Teva Investigational Site 10318 Nashville Tennessee United States 37205
29 Teva Investigational Site 10319 Salt Lake City Utah United States 84103
30 Teva Investigational Site 10330 Newport News Virginia United States 23601
31 Teva Investigational Site 10311 Roanoke Virginia United States 24018
32 Teva Investigational Site 10335 Seattle Washington United States 98122
33 Teva Investigational Site 33013 Innsbruck Austria A-6020
34 Teva Investigational Site 33014 Linz Austria 4020
35 Teva Investigational Site 33016 Wien Austria 1010
36 Teva Investigational Site 33015 Wien Austria 1090
37 Teva Investigational Site 68010 Gomel Belarus 246029
38 Teva Investigational Site 68013 Grodno Belarus 230027
39 Teva Investigational Site 68012 Minsk Belarus 220026
40 Teva Investigational Site 68009 Minsk Belarus 220114
41 Teva Investigational Site 68008 Minsk Belarus 220116
42 Teva Investigational Site 68011 Vitebsk Belarus 210023
43 Teva Investigational Site 37023 Charleroi Belgium 6000
44 Teva Investigational Site 37024 Sijsele Belgium 8340
45 Teva Investigational Site 69008 Mostar Bosnia and Herzegovina 88000
46 Teva Investigational Site 69006 Sarajevo Bosnia and Herzegovina 71000
47 Teva Investigational Site 69009 Tuzla Bosnia and Herzegovina 75000
48 Teva Investigational Site 59039 Pleven Bulgaria 5800
49 Teva Investigational Site 59040 Pleven Bulgaria 5800
50 Teva Investigational Site 59060 Pleven Bulgaria 5800
51 Teva Investigational Site 59062 Plovdiv Bulgaria 4002
52 Teva Investigational Site 59061 Ruse Bulgaria 7003
53 Teva Investigational Site 59055 Shumen Bulgaria 9700
54 Teva Investigational Site 59048 Sofia Bulgaria 1113
55 Teva Investigational Site 59052 Sofia Bulgaria 1113
56 Teva Investigational Site 59057 Sofia Bulgaria 1113
57 Teva Investigational Site 59050 Sofia Bulgaria 1142
58 Teva Investigational Site 59044 Sofia Bulgaria 1309
59 Teva Investigational Site 59063 Sofia Bulgaria 1407
60 Teva Investigational Site 59038 Sofia Bulgaria 1431
61 Teva Investigational Site 59043 Sofia Bulgaria 1431
62 Teva Investigational Site 59058 Sofia Bulgaria 1431
63 Teva Investigational Site 59041 Sofia Bulgaria 1527
64 Teva Investigational Site 59042 Sofia Bulgaria 1606
65 Teva Investigational Site 59054 Sofia Bulgaria 1606
66 Teva Investigational Site 59059 Sofia Bulgaria 1606
67 Teva Investigational Site 59045 Sofia Bulgaria 1750
68 Teva Investigational Site 59049 Stara Zagora Bulgaria 6003
69 Teva Investigational Site 59046 Varna Bulgaria 9010
70 Teva Investigational Site 59051 Veliko Tarnovo Bulgaria 5000
71 Teva Investigational Site 59053 Veliko Tarnovo Bulgaria 5100
72 Teva Investigational Site 11013 Edmonton Alberta Canada T6G 1Z1
73 Teva Investigational Site 11014 Burnaby British Columbia Canada V5G 2X6
74 Teva Investigational Site 11015 Ottawa Canada K1H 8L6
75 Teva Investigational Site 11016 Saskatoon Canada S7K 0M7
76 Teva Investigational Site 60010 Osijek Croatia 31 000
77 Teva Investigational Site 60011 Varazdin Croatia 42000
78 Teva Investigational Site 60009 Zagreb Croatia 10000
79 Teva Investigational Site 54042 Brno Czechia 602 00
80 Teva Investigational Site 54043 Havirov Czechia 736 01
81 Teva Investigational Site 54047 Hradec Kralove 3 Czechia 50003
82 Teva Investigational Site 54046 Jihlava Czechia 58633
83 Teva Investigational Site 54044 Olomouc Czechia 779 00
84 Teva Investigational Site 54045 Ostrava Czechia 702 00
85 Teva Investigational Site 54049 Praha 10 Czechia 100 31
86 Teva Investigational Site 54041 Praha Czechia 104 00
87 Teva Investigational Site 54048 Teplice Czechia 415 29
88 Teva Investigational Site 55005 Parnu Estonia 80010
89 Teva Investigational Site 55008 Tallinn Estonia EE-10138
90 Teva Investigational Site 55006 Tallinn Estonia EE-10617
91 Teva Investigational Site 55007 Tartu Estonia EE-51014
92 Teva Investigational Site 35075 Clermont-Ferrand Cedex 1 France 63003
93 Teva Investigational Site 35077 Dijon France
94 Teva Investigational Site 35073 Lille France 59000
95 Teva Investigational Site 35076 Lyon cedex 04 France 69317
96 Teva Investigational Site 35079 Nimes France 30029
97 Teva Investigational Site 81018 Tbilisi Georgia 0112
98 Teva Investigational Site 81014 Tbilisi Georgia 0141
99 Teva Investigational Site 81015 Tbilisi Georgia 0179
100 Teva Investigational Site 81019 Tbilisi Georgia 0179
101 Teva Investigational Site 81017 Tbilisi Georgia 0186
102 Teva Investigational Site 81016 Tbilisi Georgia 0194
103 Teva Investigational Site 32199 Bad Mergentheim Germany 97980
104 Teva Investigational Site 32195 Berg Germany 82335
105 Teva Investigational Site 32200 Berlin Germany 10117
106 Teva Investigational Site 32186 Berlin Germany 10437
107 Teva Investigational Site 32176 Berlin Germany 10625
108 Teva Investigational Site 32174 Berlin Germany 10713
109 Teva Investigational Site 32198 Berlin Germany 12163
110 Teva Investigational Site 32177 Bochum Germany 44791
111 Teva Investigational Site 32193 Dresden Germany 01307
112 Teva Investigational Site 32184 Erbach Germany 64711
113 Teva Investigational Site 32189 Erfurt Germany 99089
114 Teva Investigational Site 32203 Giessen Germany 35385
115 Teva Investigational Site 32202 Goettigen Germany 37075
116 Teva Investigational Site 32196 Halle (Saale) Germany 06120
117 Teva Investigational Site 32181 Hamburg Germany 20246
118 Teva Investigational Site 32179 Hamburg Germany 22083
119 Teva Investigational Site 32182 Hannover Germany 30171
120 Teva Investigational Site 32175 Ibbenburen Germany 49477
121 Teva Investigational Site 32201 Jena Germany 07743
122 Teva Investigational Site 32183 Koln Germany 50935
123 Teva Investigational Site 32190 Leipzig Germany 4103
124 Teva Investigational Site 32185 Magdeburg Germany 39120
125 Teva Investigational Site 32191 Rostock Germany 18147
126 Teva Investigational Site 32194 Teupitz Germany 15755
127 Teva Investigational Site 32173 Ulm Germany 89081
128 Teva Investigational Site 32197 Wermsdorf Germany 04773
129 Teva Investigational Site 32188 Westerstede Germany 26655
130 Teva Investigational Site 63027 Athens Greece 115 28
131 Teva Investigational Site 63024 Athens Greece 11525
132 Teva Investigational Site 63029 Chaidari Greece 12462
133 Teva Investigational Site 63026 Heraklion Greece 71110
134 Teva Investigational Site 63030 Larisa Greece 41110
135 Teva Investigational Site 63025 Thessaloniki Greece 54636
136 Teva Investigational Site 63028 Thessaloniki Greece 57010
137 Teva Investigational Site 51046 Budapest Hungary 1134
138 Teva Investigational Site 51043 Debrecen Hungary 4043
139 Teva Investigational Site 51045 Eger Hungary H-3300
140 Teva Investigational Site 51044 Kaposvar Hungary H-7400
141 Teva Investigational Site 80023 Haifa Israel 31096
142 Teva Investigational Site 80024 Haifa Israel 31096
143 Teva Investigational Site 80020 Ramat Gan Israel 5262160
144 Teva Investigational Site 80021 Tel Aviv Israel 64239
145 Teva Investigational Site 30037 Bologna Italy 40139
146 Teva Investigational Site 30031 Castelfiorentino Italy 50051
147 Teva Investigational Site 30030 Cefalu Italy 90015
148 Teva Investigational Site 30032 Chieti Italy 66100
149 Teva Investigational Site 30024 Firenze Italy 50139
150 Teva Investigational Site 30029 Gallarate Italy 21013
151 Teva Investigational Site 30023 Milano Italy 20132
152 Teva Investigational Site 30039 Milano Italy 20133
153 Teva Investigational Site 30034 Napoli Italy 80131
154 Teva Investigational Site 30027 Palermo Italy 90146
155 Teva Investigational Site 30028 Rome Italy 00149
156 Teva Investigational Site 30025 Rome Italy 00163
157 Teva Investigational Site 30026 Rome Italy 00168
158 Teva Investigational Site 30035 Rome Italy 00178
159 Teva Investigational Site 30040 Verona Italy 37134
160 Teva Investigational Site 87001 Goyang-si Korea, Republic of 410-769
161 Teva Investigational Site 87003 Seoul Korea, Republic of 03080
162 Teva Investigational Site 87002 Seoul Korea, Republic of 138-736
163 Teva Investigational Site 56006 Riga Latvia 1038
164 Teva Investigational Site 56005 Riga Latvia LV-1005
165 Teva Investigational Site 70006 Chisinau Moldova, Republic of 2001
166 Teva Investigational Site 70005 Chisinau Moldova, Republic of 2024
167 Teva Investigational Site 70008 Chisinau Moldova, Republic of 2028
168 Teva Investigational Site 66002 Podgorica Montenegro 20000
169 Teva Investigational Site 65010 Skopje North Macedonia 1000
170 Teva Investigational Site 65011 Skopje North Macedonia 1000
171 Teva Investigational Site 65012 Skopje North Macedonia 1000
172 Teva Investigational Site 53066 Bialystok Poland 15-276
173 Teva Investigational Site 53071 Bialystok Poland 15-402
174 Teva Investigational Site 53085 Bydgoszcz Poland 85-654
175 Teva Investigational Site 53084 Czestochowa Poland 42-280
176 Teva Investigational Site 53069 Gdansk Poland 80-299
177 Teva Investigational Site 53083 Gdansk Poland 80-546
178 Teva Investigational Site 53067 Gdansk Poland 80-803
179 Teva Investigational Site 53078 Grodzisk Mazowiecki Poland 05-825
180 Teva Investigational Site 53080 Katowice Poland 40-555
181 Teva Investigational Site 53081 Katowice Poland 40-650
182 Teva Investigational Site 53073 Katowice Poland 40-684
183 Teva Investigational Site 53070 Katowice Poland 40-749
184 Teva Investigational Site 53074 Katowice Poland 40-752
185 Teva Investigational Site 53064 Konskie Poland 26-200
186 Teva Investigational Site 53065 Konstancin-Jeziorna Poland 05-510
187 Teva Investigational Site 53072 Koscierzyna Poland 83-400
188 Teva Investigational Site 53063 Lodz Poland 90-324
189 Teva Investigational Site 53079 Olsztyn Poland 10-560
190 Teva Investigational Site 53068 Plewiska Poland 62-064
191 Teva Investigational Site 53076 Szczecin Poland 70-111
192 Teva Investigational Site 52045 Balotesti Romania 77015
193 Teva Investigational Site 52041 Bucharest Romania 012071
194 Teva Investigational Site 52050 Bucuresti Romania 020125
195 Teva Investigational Site 52037 Bucuresti Romania 022328
196 Teva Investigational Site 52034 Bucuresti Romania 050098
197 Teva Investigational Site 52040 Cluj-Napoca Romania 400006
198 Teva Investigational Site 52036 Cluj-Napoca Romania 400437
199 Teva Investigational Site 52038 Constanta Romania 900123
200 Teva Investigational Site 52044 Constanta Romania 900591
201 Teva Investigational Site 52048 Craiova Romania 200473
202 Teva Investigational Site 52049 Hunedoara Romania 331057
203 Teva Investigational Site 52042 Iasi Romania 700661
204 Teva Investigational Site 52039 Oradea Romania 410108
205 Teva Investigational Site 52047 Piatra-Neamt Romania 610136
206 Teva Investigational Site 52046 Sibiu Romania 550245
207 Teva Investigational Site 52035 Targu Mures Romania
208 Teva Investigational Site 52043 Timisoara Romania 100182
209 Teva Investigational Site 50130 Barnaul Russian Federation 656024
210 Teva Investigational Site 50129 Chelyabinsk Russian Federation 454021
211 Teva Investigational Site 50208 Kazan Russian Federation 420021
212 Teva Investigational Site 50148 Kemerovo Russian Federation 650061
213 Teva Investigational Site 50144 Krasnodar Russian Federation 350012
214 Teva Investigational Site 50147 Moscow Russian Federation 119021
215 Teva Investigational Site 50124 Moscow Russian Federation 127015
216 Teva Investigational Site 50133 Moscow Russian Federation 129110
217 Teva Investigational Site 50146 Moscow Russian Federation 129128
218 Teva Investigational Site 50141 Nizhny Novgorod Russian Federation 603076
219 Teva Investigational Site 50128 Nizhny Novgorod Russian Federation 603155
220 Teva Investigational Site 50131 Nizhny Novgorod Russian Federation 603155
221 Teva Investigational Site 50127 Perm Russian Federation 614990
222 Teva Investigational Site 50143 Rostov-on-Don Russian Federation 344015
223 Teva Investigational Site 50149 Rostov-on-Don Russian Federation 344022
224 Teva Investigational Site 50126 Saint Petersburg Russian Federation 191186
225 Teva Investigational Site 50140 Saint Petersburg Russian Federation 197022
226 Teva Investigational Site 50138 Samara Russian Federation 443095
227 Teva Investigational Site 50135 Saratov Russian Federation 410054
228 Teva Investigational Site 50136 Smolensk Russian Federation 214018
229 Teva Investigational Site 50137 St. Petersburg Russian Federation 194354
230 Teva Investigational Site 50125 Tomsk Russian Federation 634050
231 Teva Investigational Site 50139 Tyumen Russian Federation 625000
232 Teva Investigational Site 50134 Ufa Russian Federation 450007
233 Teva Investigational Site 50132 Volgograd Russian Federation 400138
234 Teva Investigational Site 50142 Yaroslavl Russian Federation 150030
235 Teva Investigational Site 61025 Belgrade Serbia 11000
236 Teva Investigational Site 61027 Belgrade Serbia 11000
237 Teva Investigational Site 61024 Belgrade Serbia 11080
238 Teva Investigational Site 61018 Cacak Serbia 32000
239 Teva Investigational Site 61015 Kragujevac Serbia 34000
240 Teva Investigational Site 61014 Nis Serbia 18000
241 Teva Investigational Site 61019 Sombor Serbia 25000
242 Teva Investigational Site 61016 Subotica Serbia 24000
243 Teva Investigational Site 61017 Uzice Serbia 31000
244 Teva Investigational Site 61022 Valjevo Serbia 14000
245 Teva Investigational Site 61026 Vrbas Serbia 21460
246 Teva Investigational Site 61021 Zrenjanin Serbia 23000
247 Teva Investigational Site 62012 Hlohovec Slovakia 92001
248 Teva Investigational Site 62013 Trnava Slovakia 917 75
249 Teva Investigational Site 31035 Barcelona Spain 08025
250 Teva Investigational Site 31030 Barcelona Spain 08035
251 Teva Investigational Site 31031 Getafe Spain 28905
252 Teva Investigational Site 31036 L'Hospitalet de Llobregat Spain 08907
253 Teva Investigational Site 31032 Madrid Spain 28040
254 Teva Investigational Site 31034 Madrid Spain 28046
255 Teva Investigational Site 31033 Navarro Spain 31008
256 Teva Investigational Site 31039 Oviedo Spain 33011
257 Teva Investigational Site 31037 Salt Spain 17190
258 Teva Investigational Site 58087 Chernihiv Ukraine 14001
259 Teva Investigational Site 58083 Chernivtsi Ukraine 58018
260 Teva Investigational Site 58077 Dnipropetrovsk Ukraine 49044
261 Teva Investigational Site 58088 Ivano-Frankivsk Ukraine 76008
262 Teva Investigational Site 58076 Ivano-Frankivsk Ukraine
263 Teva Investigational Site 58116 Kharkiv Ukraine 61068
264 Teva Investigational Site 58084 Kharkiv Ukraine 61103
265 Teva Investigational Site 58089 Kiev Ukraine 04112
266 Teva Investigational Site 58073 Kyiv Ukraine 01601
267 Teva Investigational Site 58078 Kyiv Ukraine 03110
268 Teva Investigational Site 58081 Kyiv Ukraine 03115
269 Teva Investigational Site 58115 Lviv Ukraine 79013
270 Teva Investigational Site 58086 Lviv Ukraine 79059
271 Teva Investigational Site 58074 Odesa Ukraine 65025
272 Teva Investigational Site 58085 Odessa Ukraine 65014
273 Teva Investigational Site 58082 Poltava Ukraine 36024
274 Teva Investigational Site 58080 Simferopol Ukraine 95000
275 Teva Investigational Site 58072 Vinnytsya Ukraine 21005
276 Teva Investigational Site 58079 Zaporizhzhya Ukraine 69035
277 Teva Investigational Site 58075 Zaporizhzhya Ukraine 69600
278 Teva Investigational Site 34015 Glasgow United Kingdom G51 4TF
279 Teva Investigational Site 34011 Liverpool United Kingdom B0T 1K0
280 Teva Investigational Site 34010 Liverpool United Kingdom L9 7LJ
281 Teva Investigational Site 34019 London United Kingdom E1 1BB
282 Teva Investigational Site 34016 Salford United Kingdom M6 8HD
283 Teva Investigational Site 34017 Sheffield United Kingdom S10 2JF
284 Teva Investigational Site 34013 Stoke-on-Trent United Kingdom ST4 6QG

Sponsors and Collaborators

  • Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

  • Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT01707992
Other Study ID Numbers:
  • LAQ-MS-305
  • 2012-003647-30
First Posted:
Oct 16, 2012
Last Update Posted:
Nov 9, 2021
Last Verified:
Nov 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail The study was conducted at 215 sites in 29 countries.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg Active Treatment Phase: Laquinimod 0.6 mg Active Treatment Phase: Laquinimod 1.2 mg Active Treatment Phase: Off Drug
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 milligrams [mg]) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months. Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months. Participants who were discontinued from treatment with laquinimod 1.2 mg during the placebo-controlled phase due to sponsor decision after 01 January 2016 continued to the active-treatment phase off drug for 24 months.
Period Title: Placebo-Controlled Phase (24 Months)
STARTED 740 727 732 0 0 0
COMPLETED 596 623 532 0 0 0
NOT COMPLETED 144 104 200 0 0 0
Period Title: Placebo-Controlled Phase (24 Months)
STARTED 0 0 0 891 504 215
COMPLETED 0 0 0 7 10 0
NOT COMPLETED 0 0 0 884 494 215

Baseline Characteristics

Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg Total
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months. Total of all reporting groups
Overall Participants 740 727 732 2199
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
35.9
(8.95)
36.8
(9.25)
36.1
(9.22)
36.3
(9.14)
Age, Customized (Count of Participants)
Adults (18-64 years)
740
100%
727
100%
732
100%
2199
100%
Sex: Female, Male (Count of Participants)
Female
488
65.9%
510
70.2%
475
64.9%
1473
67%
Male
252
34.1%
217
29.8%
257
35.1%
726
33%
Race (Count of Participants)
White
724
97.8%
712
97.9%
717
98%
2153
97.9%
Black
3
0.4%
3
0.4%
3
0.4%
9
0.4%
Asian
3
0.4%
2
0.3%
3
0.4%
8
0.4%
Other
10
1.4%
8
1.1%
9
1.2%
27
1.2%
Missing
0
0%
2
0.3%
0
0%
2
0.1%
Kurtzke's Expanded Disability Status Scale (EDSS) Score (Count of Participants)
Less than or equal to (<=) 4.0
653
88.2%
635
87.3%
644
88%
1932
87.9%
Greater than (>) 4.0
87
11.8%
90
12.4%
88
12%
265
12.1%
Missing
0
0%
2
0.3%
0
0%
2
0.1%
Normalized Brain Volume (milliliters (mL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters (mL)]
1437.2
(93.37)
1433.0
(92.49)
1434.4
(93.41)
1434.9
(93.07)

Outcome Measures

1. Primary Outcome
Title Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months)
Description Time to CDP was defined as the time to a sustained increase in Kurtzke's Expanded Disability Status Scale (EDSS) score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least three months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]). Data is presented as distribution of CDP (number of participants with CDP) sustained for 3 months.
Time Frame Baseline to Month 24

Outcome Measure Data

Analysis Population Description
ITT analysis set included all randomized participants.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 740 727 732
Count of Participants [Participants]
73
9.9%
66
9.1%
69
9.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo-Controlled Phase: Placebo, Placebo-Controlled Phase: Laquinimod 0.6 mg
Comments The primary analysis for the comparison between laquinimod 0.6 mg versus placebo was conducted using the baseline adjusted Cox proportional hazards model. Categorical EDSS at baseline (less than or equal to [<=] 4 or greater than [>] 4), country/geographical region (CGR), categorical age at baseline (<=38 or >38), and T2 volume at baseline were included as covariates in the model.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value = 0.7057
Comments Threshold for significance at 0.05 level.
Method Cox proportional hazards model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.937
Confidence Interval (2-Sided) 95%
0.668 to 1.313
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15
Description Brain atrophy was defined by the percent change in brain volume from baseline to Month 15. For participants who prematurely discontinued treatment or completed the placebo-controlled phase before Month 15, the last available measurement was used, provided it was performed at least 9 months following the initiation of study drug.
Time Frame Baseline, Month 15

Outcome Measure Data

Analysis Population Description
The modified intent-to-treat 1 (mITT1) analysis set included data from all randomized participants at the Month 15 visit. Here, 'Overall number of participants analyzed' = Participants evaluable for this outcome measure.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 619 636 616
Mean (Standard Deviation) [percent change]
-0.8
(1.02)
-0.4
(1.01)
-0.4
(1.05)
3. Secondary Outcome
Title Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse)
Description Relapse was defined as appearance of one or more new neurological abnormalities or reappearance or worsening of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in absence of fever or any infection) and immediately preceded by an improving neurological state of at least 30 days from onset of previous relapse. An event was counted as a relapse only when the participant's symptoms were accompanied by observed objective neurological changes, consistent with an increase of at least 0.5 in EDSS; or one grade in score of 2 or more of 7 Functional Systems (FS) (excluding changes in bowel or bladder function or cognition); or 2 grades in score of one of the FS as compared to previous evaluation. EDSS assesses disability in 8 FS with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of relapsing participants (number of participants with confirmed relapse).
Time Frame Baseline to Month 24

Outcome Measure Data

Analysis Population Description
ITT analysis set included all randomized participants.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 740 727 732
Count of Participants [Participants]
332
44.9%
269
37%
222
30.3%
4. Secondary Outcome
Title Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months)
Description Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 6 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 6 months.
Time Frame Baseline to Month 24

Outcome Measure Data

Analysis Population Description
ITT analysis set included all randomized participants.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 740 727 732
Count of Participants [Participants]
49
6.6%
49
6.7%
51
7%
5. Secondary Outcome
Title Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months)
Description Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 9 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 9 months.
Time Frame Baseline to Month 24

Outcome Measure Data

Analysis Population Description
ITT analysis set included all randomized participants.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 740 727 732
Count of Participants [Participants]
38
5.1%
38
5.2%
39
5.3%
6. Other Pre-specified Outcome
Title Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs)
Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.
Time Frame Baseline up to Month 24

Outcome Measure Data

Analysis Population Description
Safety analysis set included all participants who were randomized and received at least one dose of study drug.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 740 727 732
Count of Participants [Participants]
546
73.8%
565
77.7%
575
78.6%
7. Other Pre-specified Outcome
Title Active-Treatment Phase: Number of Participants With AEs
Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.
Time Frame Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

Outcome Measure Data

Analysis Population Description
Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
Arm/Group Title Active Treatment Phase: Laquinimod 0.6 mg Active Treatment Phase: Laquinimod 1.2 mg
Arm/Group Description Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.
Measure Participants 891 504
Count of Participants [Participants]
442
59.7%
241
33.1%
8. Other Pre-specified Outcome
Title Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities
Description Clinically significant vital signs abnormalities included: Pulse rate: greater than or equal to (>=) 120 beats per minute (bpm) and increase from baseline of >=30 bpm, <=45 bpm and decrease from baseline of >=30 bpm; Systolic blood pressure: >=180 millimeters of mercury (mmHg) and increase from baseline of >=30 mmHg, <=90 and decrease from baseline of >=30 mmHg; Diastolic blood pressure: >=100 mmHg and increase from baseline of >=20 mmHg, <=50 mmHg and decrease from baseline of >=20 mmHg.
Time Frame Baseline up to Week 24

Outcome Measure Data

Analysis Population Description
Safety analysis set included all participants who were randomized and received at least one dose of study drug.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 740 727 732
Count of Participants [Participants]
21
2.8%
21
2.9%
29
4%
9. Other Pre-specified Outcome
Title Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities
Description Clinically significant vital signs abnormalities included: Pulse rate: >=120 bpm and increase from baseline of >=30 bpm, <=45 bpm and decrease from baseline of >=30 bpm; Systolic blood pressure: >=180 mmHg and increase from baseline of >=30 mmHg, <=90 and decrease from baseline of >=30 mmHg; Diastolic blood pressure: >=100 mmHg and increase from baseline of >=20 mmHg, <=50 mmHg and decrease from baseline of >=20 mmHg.
Time Frame Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

Outcome Measure Data

Analysis Population Description
Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
Arm/Group Title Active Treatment Phase: Laquinimod 0.6 mg Active Treatment Phase: Laquinimod 1.2 mg
Arm/Group Description Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.
Measure Participants 891 504
Count of Participants [Participants]
17
2.3%
7
1%
10. Other Pre-specified Outcome
Title Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Description ECG parameters included: PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.
Time Frame Baseline, Endpoint (Month 24)

Outcome Measure Data

Analysis Population Description
Safety analysis set included all participants who were randomized and received at least one dose of study drug. Here, 'Overall number of participants analyzed=participants evaluable for this outcome measure.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 734 723 724
Normal - Normal
463
62.6%
467
64.2%
470
64.2%
Normal - Abnormal NCS
139
18.8%
124
17.1%
126
17.2%
Normal - Abnormal CS
0
0%
6
0.8%
5
0.7%
Abnormal NCS - Normal
32
4.3%
27
3.7%
28
3.8%
Abnormal NCS - Abnormal NCS
98
13.2%
96
13.2%
90
12.3%
Abnormal NCS - Abnormal CS
1
0.1%
1
0.1%
2
0.3%
Abnormal CS - Normal
0
0%
1
0.1%
0
0%
Abnormal CS - Abnormal NCS
0
0%
0
0%
0
0%
Abnormal CS - Abnormal CS
1
0.1%
1
0.1%
3
0.4%
11. Other Pre-specified Outcome
Title Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters
Description ECG parameters included: PR interval, QRS interval, QTcF and QTcB. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.
Time Frame Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase), endpoint (Month 24 of active-treatment phase)

Outcome Measure Data

Analysis Population Description
Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase and had ECG shift from baseline data available.
Arm/Group Title Active Treatment Phase: Laquinimod 0.6 mg Active Treatment Phase: Laquinimod 1.2 mg
Arm/Group Description Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.
Measure Participants 888 501
Normal - Normal
641
86.6%
353
48.6%
Normal - Abnormal NCS
137
18.5%
80
11%
Normal - Abnormal CS
7
0.9%
5
0.7%
Abnormal NCS - Normal
18
2.4%
17
2.3%
Abnormal NCS - Abnormal NCS
81
10.9%
45
6.2%
Abnormal NCS - Abnormal CS
4
0.5%
0
0%
Abnormal CS - Normal
0
0%
0
0%
Abnormal CS - Abnormal NCS
0
0%
0
0%
Abnormal CS - Abnormal CS
0
0%
1
0.1%
12. Other Pre-specified Outcome
Title Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry
Description Potentially clinically significant serum chemistry abnormalities included: Glucose <=3 and >=13.88 millimoles per liter (mmol/L); Alanine aminotransferase (ALT) (in units per liter [U/L]), aspartate aminotransferase (AST) (in U/L), alkaline phosphatase (in U/L), gamma-glutamyltransferase (GGT) (in U/L), creatine phosphokinase (CPK) (in U/L), C-reactive protein (CRP) (in milligrams per liter [mg/L]), pancreatic amylase (in U/L)>=3 * upper limit of normal (ULN); Fibrinogen >=6 grams per liter (gm/L); Sodium <=130 and >=150 mmol/L; Potassium <=3.2 and >=5.5 mmol/L; Calcium <=1.87 and >=2.75 mmol/L; Phosphate <=0.65 and >=1.61 mmol/L.
Time Frame Baseline up to Month 24

Outcome Measure Data

Analysis Population Description
Safety analysis set included all participants who were randomized and received at least one dose of study drug. Here, 'Overall number of participants analyzed'=participants evaluable for this outcome measure.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 736 723 724
Count of Participants [Participants]
157
21.2%
165
22.7%
187
25.5%
13. Other Pre-specified Outcome
Title Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry
Description Potentially clinically significant serum chemistry abnormalities included: Glucose <=3 and >=13.88 mmol/L; ALT (in U/L), AST (in U/L), alkaline phosphatase (in U/L), GGT (in U/L), CPK (in U/L), CRP (in mg/L), pancreatic amylase (in U/L)>=3 * ULN; Fibrinogen >=6 gm/L; Sodium <=130 and >=150 mmol/L; Potassium <=3.2 and >=5.5 mmol/L; Calcium <=1.87 and >=2.75 mmol/L; Phosphate <=0.65 and >=1.61 mmol/L; Blood urea nitrogen (in mmol/L); Total bilirubin >=28 micromols per liter (micromols/L); Creatinine >=117 micromols/L; Albumin <=25 gm/L.
Time Frame Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

Outcome Measure Data

Analysis Population Description
Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
Arm/Group Title Active Treatment Phase: Laquinimod 0.6 mg Active Treatment Phase: Laquinimod 1.2 mg
Arm/Group Description Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.
Measure Participants 891 504
Count of Participants [Participants]
887
119.9%
501
68.9%
14. Other Pre-specified Outcome
Title Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values
Description Potentially clinically significant hematological abnormalities included: Hemoglobin <=11.5 grams per deciliter (gm/dL) in males and <=10 gm/dL in females; White blood cells (WBCs) count <=2.5 and >=21*10^9 per liter (L); Absolute neutrophil count (ANC) <=1.49*10^9 per L; Platelet count <=100 and >=600*10^9 per L.
Time Frame Baseline up to Month 24

Outcome Measure Data

Analysis Population Description
Safety analysis set included all participants who were randomized and received at least one dose of study drug. Here, 'Overall number of participants analyzed'=participants evaluable for this outcome measure.
Arm/Group Title Placebo-Controlled Phase: Placebo Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg
Arm/Group Description Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months.
Measure Participants 735 723 723
Count of Participants [Participants]
71
9.6%
78
10.7%
83
11.3%
15. Other Pre-specified Outcome
Title Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values
Description Potentially clinically significant hematological abnormalities included: Hemoglobin <=11.5, >=20 gm/dL in males, and <=10, >=18.5 gm/dL in females; WBCs count <=2.5 and >=21*10^9 per L; ANC <=1.49*10^9 per L; Platelet count <=100 and >=600*10^9 per L.
Time Frame Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase

Outcome Measure Data

Analysis Population Description
Safety analysis set in active-treatment phase included all participants who completed placebo-controlled phase on treatment and continued to either of the 2 laquinimod treatments during active-treatment phase.
Arm/Group Title Active Treatment Phase: Laquinimod 0.6 mg Active Treatment Phase: Laquinimod 1.2 mg
Arm/Group Description Participants who completed the placebo-controlled phase on placebo and on laquinimod 0.6 mg treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on placebo and on laquinimod 1.2 mg treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.
Measure Participants 891 504
Count of Participants [Participants]
886
119.7%
499
68.6%

Adverse Events

Time Frame Adverse events were collected for the procedure and at each follow-up visit at 2 weeks, 6 weeks, 12 weeks, 24 weeks, and 52 weeks post-treatment.
Adverse Event Reporting Description
Arm/Group Title Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg Placebo-Controlled Phase: Placebo Active Treatment Phase: Early Laquinimod 0.6 mg Active Treatment Phase: Early Laquinimod 1.2 mg Active Treatment Phase: Off Drug Active Treatment Phase: From Placebo to Laquinimod 0.6 mg Active Treatment Phase: From Placebo to Laquinimod 1.2 mg
Arm/Group Description Participants received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for up to 24 months. Participants received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for up to 24 months. Participants received 2 capsules of placebo (matched to laquinimod 0.6 mg) once daily orally for up to 24 months. Participants who completed the placebo-controlled phase on laquinimod 0.6 mg treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on laquinimod 1.2 mg treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months. Participants who were discontinued from treatment with laquinimod 1.2 mg during the placebo-controlled phase due to sponsor decision after 01 January 2016, continued to the active-treatment phase off drug for 24 months. Participants who completed the placebo-controlled phase on placebo treatment group after 01 January 2016, received 1 capsule of laquinimod 0.6 mg and 1 capsule of matching placebo once daily orally for 24 months. Participants who completed the placebo-controlled phase on placebo treatment group prior to 01 January 2016, received laquinimod 1.2 mg (2 capsules of laquinimod 0.6 mg each) once daily orally for 24 months.
All Cause Mortality
Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg Placebo-Controlled Phase: Placebo Active Treatment Phase: Early Laquinimod 0.6 mg Active Treatment Phase: Early Laquinimod 1.2 mg Active Treatment Phase: Off Drug Active Treatment Phase: From Placebo to Laquinimod 0.6 mg Active Treatment Phase: From Placebo to Laquinimod 1.2 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/727 (0.1%) 1/732 (0.1%) 2/740 (0.3%) 2/580 (0.3%) 0/268 (0%) 0/215 (0%) 0/311 (0%) 0/236 (0%)
Serious Adverse Events
Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg Placebo-Controlled Phase: Placebo Active Treatment Phase: Early Laquinimod 0.6 mg Active Treatment Phase: Early Laquinimod 1.2 mg Active Treatment Phase: Off Drug Active Treatment Phase: From Placebo to Laquinimod 0.6 mg Active Treatment Phase: From Placebo to Laquinimod 1.2 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 57/727 (7.8%) 49/732 (6.7%) 43/740 (5.8%) 24/580 (4.1%) 10/268 (3.7%) 5/215 (2.3%) 5/311 (1.6%) 9/236 (3.8%)
Blood and lymphatic system disorders
Hypochromic anaemia 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Immune thrombocytopenic purpura 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Iron deficiency anaemia 1/727 (0.1%) 1 0/732 (0%) 0 2/740 (0.3%) 2 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Lymphadenitis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Thrombocytopenia 1/727 (0.1%) 1 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cardiac disorders
Acute myocardial infarction 0/727 (0%) 0 4/732 (0.5%) 4 0/740 (0%) 0 1/580 (0.2%) 1 1/268 (0.4%) 1 1/215 (0.5%) 1 0/311 (0%) 0 0/236 (0%) 0
Angina pectoris 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Arteriosclerosis coronary artery 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Atrial fibrillation 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cardiogenic shock 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cardiovascular insufficiency 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Coronary artery occlusion 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 1/215 (0.5%) 1 0/311 (0%) 0 0/236 (0%) 0
Coronary artery stenosis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Myocardial infarction 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 2/580 (0.3%) 2 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Myocardial ischaemia 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Ear and labyrinth disorders
Vertigo 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Gastrointestinal disorders
Abdominal pain 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Coeliac disease 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Colitis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Duodenal perforation 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Enteritis 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Gastric polyps 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Gastritis 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Gastritis erosive 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Gastrointestinal inflammation 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Gastrooesophageal reflux disease 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Inguinal hernia 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pancreatic necrosis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pancreatitis 0/727 (0%) 0 4/732 (0.5%) 4 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pancreatitis acute 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pancreatitis chronic 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Periodontal inflammation 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Peritoneal adhesions 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Peritoneal haemorrhage 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Autoimmune pancreatitis 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Ileus 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
General disorders
Asthenia 0/727 (0%) 0 1/732 (0.1%) 2 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Fatigue 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Gait disturbance 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Non-cardiac chest pain 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pyrexia 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Strangulated hernia 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hepatobiliary disorders
Cholecystitis 0/727 (0%) 0 3/732 (0.4%) 3 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cholecystitis acute 2/727 (0.3%) 2 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cholecystitis chronic 2/727 (0.3%) 2 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cholelithiasis 1/727 (0.1%) 1 0/732 (0%) 0 2/740 (0.3%) 2 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cholelithiasis obstructive 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cholestasis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Drug-induced liver injury 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hepatitis cholestatic 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hepatotoxicity 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hepatitis toxic 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Immune system disorders
Drug hypersensitivity 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 1/311 (0.3%) 1 0/236 (0%) 0
Sarcoidosis 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Infections and infestations
Abscess oral 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Appendicitis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Bronchitis 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cholecystitis infective 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Chronic sinusitis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Chronic tonsillitis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Endometritis 1/727 (0.1%) 1 0/732 (0%) 0 2/740 (0.3%) 2 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Enterovirus infection 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Erysipelas 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Helicobacter gastritis 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hepatitis B 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Herpes zoster oticus 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Infected dermal cyst 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 1/311 (0.3%) 1 0/236 (0%) 0
Ovarian abscess 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Peritonitis 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pilonidal cyst 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pneumonia 2/727 (0.3%) 2 2/732 (0.3%) 2 1/740 (0.1%) 1 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pneumonia bacterial 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pyelonephritis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pyelonephritis acute 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pyelonephritis chronic 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Salpingitis 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Salpingo-oophoritis 2/727 (0.3%) 2 0/732 (0%) 0 2/740 (0.3%) 2 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Sepsis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Sinusitis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Urinary bladder abscess 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Urinary tract infection 1/727 (0.1%) 1 1/732 (0.1%) 1 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Uterine infection 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hepatitis viral 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Tuberculosis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Injury, poisoning and procedural complications
Ankle fracture 0/727 (0%) 0 2/732 (0.3%) 2 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 1/311 (0.3%) 1 0/236 (0%) 0
Bone contusion 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Brain contusion 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cartilage injury 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Craniocerebral injury 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Fall 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Femoral neck fracture 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 1/311 (0.3%) 1 0/236 (0%) 0
Femur fracture 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Head injury 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Humerus fracture 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Jaw fracture 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Meniscus injury 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Multiple injuries 1/727 (0.1%) 1 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Poisoning deliberate 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Postoperative adhesion 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pubis fracture 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Radius fracture 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Road traffic accident 2/727 (0.3%) 2 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Skull fracture 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Skull fractured base 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Subdural haematoma 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Thermal burn 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Thoracic vertebral fracture 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Toxicity to various agents 1/727 (0.1%) 1 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Traumatic liver injury 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Ulna fracture 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Upper limb fracture 1/727 (0.1%) 1 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Intentional overdose 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Investigations
Alpha 1 foetoprotein abnormal 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Blood creatine phosphokinase increased 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 1/215 (0.5%) 1 0/311 (0%) 0 0/236 (0%) 0
Hepatic enzyme increased 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Nuclear magnetic resonance imaging brain abnormal 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Troponin increased 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Metabolism and nutrition disorders
Diabetes mellitus 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Diabetes mellitus inadequate control 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Diabetic ketoacidosis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Metabolic disorder 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Type 1 diabetes mellitus 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cervical spinal stenosis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Femoroacetabular impingement 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Intervertebral disc protrusion 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Musculoskeletal chest pain 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Neck pain 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Osteoarthritis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Osteonecrosis 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pain in extremity 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Spinal osteoarthritis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Spinal pain 1/727 (0.1%) 2 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Benign breast neoplasm 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Benign neoplasm of adrenal gland 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Chronic lymphocytic leukaemia 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Clear cell renal cell carcinoma 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Fibroadenoma of breast 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Haemangioma 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Metastases to central nervous system 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 1/215 (0.5%) 1 0/311 (0%) 0 0/236 (0%) 0
Metastases to chest wall 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 1/215 (0.5%) 1 0/311 (0%) 0 0/236 (0%) 0
Papilloma 1/727 (0.1%) 1 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Salivary gland adenoma 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Thyroid cancer 1/727 (0.1%) 1 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Uterine leiomyoma 5/727 (0.7%) 5 0/732 (0%) 0 2/740 (0.3%) 2 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Bone sarcoma 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Nervous system disorders
Altered state of consciousness 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Coma 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Diabetic neuropathy 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Haemorrhagic stroke 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 1/215 (0.5%) 1 0/311 (0%) 0 0/236 (0%) 0
Headache 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Ischaemic stroke 0/727 (0%) 0 1/732 (0.1%) 1 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Multiple sclerosis 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Multiple sclerosis relapse 2/727 (0.3%) 2 1/732 (0.1%) 1 7/740 (0.9%) 7 2/580 (0.3%) 2 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Neurological decompensation 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Neuromyelitis optica spectrum disorder 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Psychomotor hyperactivity 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Seizure 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Syncope 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Trigeminal neuralgia 1/727 (0.1%) 1 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Status epilepticus 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous 1/727 (0.1%) 1 0/732 (0%) 0 2/740 (0.3%) 2 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Foetal growth abnormality 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Unintended pregnancy 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Abortion 0/727 (0%) 0 2/732 (0.3%) 2 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Abortion missed 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Abortion threatened 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Psychiatric disorders
Acute psychosis 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Affective disorder 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Confusional state 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Major depression 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Persecutory delusion 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Personality change due to a general medical condition 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Psychotic disorder 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Schizophrenia 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Suicidal ideation 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Completed suicide 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Suicide attempt 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Renal and urinary disorders
Nephrolithiasis 1/727 (0.1%) 1 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hydronephrosis 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Reproductive system and breast disorders
Acquired hydrocele 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 1/268 (0.4%) 1 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Adnexal torsion 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Cervix disorder 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Fallopian tube cyst 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Menometrorrhagia 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Metrorrhagia 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Ovarian cyst 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 1/311 (0.3%) 1 0/236 (0%) 0
Ovarian haemorrhage 1/727 (0.1%) 2 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Polycystic ovaries 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Interstitial lung disease 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 1/236 (0.4%) 1
Lung disorder 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Nasal septum deviation 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pleurisy 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Pneumothorax spontaneous 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Vasomotor rhinitis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Bronchiectasis 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Skin and subcutaneous tissue disorders
Urticaria 2/727 (0.3%) 2 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Surgical and medical procedures
Hospitalisation 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 1/215 (0.5%) 1 0/311 (0%) 0 0/236 (0%) 0
Vascular disorders
Deep vein thrombosis 0/727 (0%) 0 1/732 (0.1%) 1 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Embolism arterial 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Hypertension 0/727 (0%) 0 0/732 (0%) 0 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Orthostatic hypotension 0/727 (0%) 0 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Thrombophlebitis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 1/580 (0.2%) 1 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Varicose vein 0/727 (0%) 0 1/732 (0.1%) 1 1/740 (0.1%) 1 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Vasculitis 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Venous thrombosis limb 1/727 (0.1%) 1 0/732 (0%) 0 0/740 (0%) 0 0/580 (0%) 0 0/268 (0%) 0 0/215 (0%) 0 0/311 (0%) 0 0/236 (0%) 0
Other (Not Including Serious) Adverse Events
Placebo-Controlled Phase: Laquinimod 0.6 mg Placebo-Controlled Phase: Laquinimod 1.2 mg Placebo-Controlled Phase: Placebo Active Treatment Phase: Early Laquinimod 0.6 mg Active Treatment Phase: Early Laquinimod 1.2 mg Active Treatment Phase: Off Drug Active Treatment Phase: From Placebo to Laquinimod 0.6 mg Active Treatment Phase: From Placebo to Laquinimod 1.2 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 262/727 (36%) 286/732 (39.1%) 243/740 (32.8%) 102/580 (17.6%) 46/268 (17.2%) 35/215 (16.3%) 43/311 (13.8%) 43/236 (18.2%)
Blood and lymphatic system disorders
Anaemia 28/727 (3.9%) 32 43/732 (5.9%) 50 30/740 (4.1%) 35 22/580 (3.8%) 25 13/268 (4.9%) 16 7/215 (3.3%) 7 9/311 (2.9%) 9 9/236 (3.8%) 12
Infections and infestations
Nasopharyngitis 63/727 (8.7%) 90 60/732 (8.2%) 86 63/740 (8.5%) 91 40/580 (6.9%) 52 14/268 (5.2%) 20 8/215 (3.7%) 13 11/311 (3.5%) 13 11/236 (4.7%) 13
Respiratory tract infection viral 32/727 (4.4%) 54 31/732 (4.2%) 37 39/740 (5.3%) 56 14/580 (2.4%) 19 7/268 (2.6%) 9 3/215 (1.4%) 3 3/311 (1%) 3 5/236 (2.1%) 6
Investigations
Amylase increased 17/727 (2.3%) 20 38/732 (5.2%) 43 18/740 (2.4%) 19 6/580 (1%) 7 2/268 (0.7%) 2 2/215 (0.9%) 2 6/311 (1.9%) 6 5/236 (2.1%) 8
Musculoskeletal and connective tissue disorders
Back pain 54/727 (7.4%) 74 85/732 (11.6%) 110 39/740 (5.3%) 47 12/580 (2.1%) 14 8/268 (3%) 10 9/215 (4.2%) 10 1/311 (0.3%) 1 12/236 (5.1%) 14
Nervous system disorders
Headache 122/727 (16.8%) 238 131/732 (17.9%) 227 116/740 (15.7%) 222 22/580 (3.8%) 38 8/268 (3%) 14 10/215 (4.7%) 13 14/311 (4.5%) 25 10/236 (4.2%) 15

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.

Results Point of Contact

Name/Title Director, Clinical Research
Organization Teva Branded Pharmaceutical Products, R&D Inc.
Phone 215-591-3000
Email info.era-clinical@teva.de
Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT01707992
Other Study ID Numbers:
  • LAQ-MS-305
  • 2012-003647-30
First Posted:
Oct 16, 2012
Last Update Posted:
Nov 9, 2021
Last Verified:
Nov 1, 2021