BRAVO Study: Laquinimod Double-blind Placebo-controlled Study in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) With a Rater Blinded Reference Arm of Interferon β-1a (Avonex®)
Study Details
Study Description
Brief Summary
The study aims to compare the effect of daily oral treatment of laquinimod capsules 0.6 milligrams (mg) with the effect of placebo capsules (capsules that contain no active medication) as well as with the effect of an existing Multiple Sclerosis (MS) injectable drug: Interferon β-1a (Avonex®).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Placebo Comparator: Placebo Participants will receive 1 capsule of placebo matching to laquinimod orally once daily for 24 months. |
Drug: Placebo
Placebo matching to laquinimod will be administered per schedule specified in the arm description.
|
Experimental: Laquinimod Participants will receive 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. |
Drug: Laquinimod
Laquinimod will be administered per dose and schedule specified in the arm description.
|
Active Comparator: Avonex® Participants will receive an injection of Avonex® 30 micrograms (mcg) given intramuscularly (IM) once weekly for 24 months. |
Drug: Avonex®
Avonex® will be administered per dose and schedule specified in the arm description.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Annualized Rate of Confirmed Relapses [Baseline up to Month 24]
A relapse was defined as the appearance of new neurological abnormalities or the reappearance of previously observed neurological abnormalities; lasting at least 48 hours and immediately preceded by an improved neurological state of ≥30 days from onset of previous relapse, accompanied by observed objective neurological changes (an increase of ≥0.5 in Expanded Disability Status Scale [EDSS] score, or an increase of 1 grade in the score of 2 or more of the 7 Functional Systems [FS], or an increase of 2 grades in the score of 1 FS as compared to the previous evaluation). Total number of confirmed relapses during the treatment period was divided by the sum of number of days on study in the treatment period and then multiplied by the number of days in the year to calculate the annualized relapse rate. Annualized relapse rate was derived from a baseline-adjusted negative binomial regression.
Secondary Outcome Measures
- Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score [Baseline, Month 24]
The Multiple Sclerosis Functional Composite is an instrument assessing disability that consists of 3 clinical assessments. The 3 are Timed 25-Foot Walk, 9-Hole Peg Test which measures upper extremity (arm and hand) function, and PASAT (Paced Auditory Serial Addition Test) which is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. A Z-score is used to define a common metric from the 3 assessments that constitute the MSFC score. The study's population at baseline was used as reference population for the Z-score calculation. A Z-score of 0 represents the population mean at baseline. Higher Z-scores correspond to an improved outcome.
- Percent Change From Baseline in Brain Volume [Baseline, Month 24]
Change in brain volume was derived from MRI scans obtained at baseline and at Month 24.
- Accumulation of Physical Disability Measured by the Number of Participants With Confirmed Progression of EDSS [Baseline up to Month 24]
A confirmed progression of EDSS was defined as a 1 point increase from baseline on EDSS score if baseline EDSS was between 0 and 5.0, or a 0.5 point increase if baseline EDSS was 5.5, confirmed 3 months later. 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 confirmed progression (number of participants with confirmed progression of EDSS) sustained for 3 months. Progression could not be confirmed during a relapse.
Other Outcome Measures
- Change From Baseline in General Health Status as Assessed by the Short-Form General Health Survey (SF-36) Patient-Reported Questionnaire For Physical Component Summary (PCS) Scores [Baseline, Month 6, Month 12, Month 18, Month 24]
The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Items 1 to 4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item were summed and averaged (range: 0=worst to 100=best). Higher scores represent better health status and functional ability.
- Change From Baseline in General Health Status as Assessed by the Short-Form General Health Survey (SF-36) Patient-Reported Questionnaire For Mental Component Summary (MCS) Scores [Baseline, Month 6, Month 12, Month 18, Month 24]
The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Items 1 to 4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item were summed and averaged (range: 0=worst to 100=best). Higher scores represent better health status and functional ability.
- Cumulative Number of New or Enlarging Hypointense Lesions on Enhanced T1 Scans [Months 12 and 24]
The cumulative number of new or enlarging hypointense lesions was calculated as the sum of the numbers of new or enlarging hypointense lesions observed on scans taken at Months 12 and 24.
- Cumulative Number of Enhancing Lesions on T1-Weighted Images [Months 12 and 24]
The cumulative number of T1 Gadolinium (Gd)-enhancing lesions was calculated as the sum of the numbers of Gd-enhancing lesions observed on scans taken at Months 12 and 24.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria [Ann Neurol 2005: 58:840-846], with a relapsing-remitting disease course.
-
Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
-
Subjects must be in a stable neurological condition between screening (month -1) and baseline visits (month 0).
-
Subjects must have had experienced one of the following:
-
At least one documented relapse in the 12 months prior to screening
-
At least two documented relapses in the 24 months prior to screening
-
One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.
-
Subjects must be between 18 and 55 years of age, inclusive.
-
Subjects must have disease duration of at least 6 months (from first symptom) prior to screening.
-
Women of child-bearing potential must practice 2 acceptable methods of birth control [acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide)].
-
Subjects must be willing and able to comply with the protocol requirements for the duration of the study.
Exclusion Criteria:
-
An onset of relapse or any treatment with corticosteroids (intravenous [iv], intramuscular [im] and/or per os [po]) or ACTH between month -1 (screening) and 0 (baseline).
-
Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
-
Use of immunosuppressive (including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
-
Previous use of either of the following: natalizumab (Tysabri®), cladribine or laquinimod.
-
Previous treatment with glatiramer acetate (Copaxone®) or IVIG within 3 months prior to screening visit.
-
Previous treatment with Interferon beta-1a (Avonex® or Rebif®) or Interferon beta-1b (Betaseron®).
-
Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months prior to screening visit.
-
Previous total body irradiation or total lymphoid irradiation.
-
Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
-
A known history of tuberculosis.
-
Acute infection 2 weeks prior to baseline visit.
-
Major trauma or surgery 2 weeks prior to baseline visit.
-
A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis).
-
A carrier state of factor V Leiden mutation (either homo- or heterozygous) by history or as disclosed at screening.
-
Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit.
-
Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (see detailed list of drugs in protocol) (1 month for fluoxetine).
-
Use of amiodarone within 2 years prior to screening visit.
-
Pregnancy or breastfeeding.
-
Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:
-
A cardiovascular or pulmonary disorder that cannot be well-controlled by standard treatment permitted by the study protocol.
-
A gastrointestinal disorder that may affect the absorption of study medication.
-
Renal, metabolic, endocrinological or hematological diseases.
-
Any form of chronic liver disease, including known non-alcoholic steatohepatitis.
-
A ≥2xULN serum elevation of either of the following at screening: ALT, AST or direct bilirubin.
-
A QTc interval (obtained from either two ECG recordings at screening or from the mean value calculated from three measurements at baseline visit) which is ≥450msec.
-
A family history of Long-QT syndrome.
-
A history of drug and/or alcohol abuse.
-
Major psychiatric disorder.
-
A history of a convulsive disorder.
-
Known hypersensitivity to either of the following: mannitol, meglumine or sodium stearyl fumarate.
-
Known hypersensitivity that would preclude administration of laquinimod.
-
The subject's inability to give informed consent, or to complete the study, or if the subject is considered by the investigator to be, for any reason, an unsuitable candidate for this study.
-
A known history of sensitivity to Gadolinium.
-
Inability to successfully undergo MRI scanning.
-
A known history of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation of Avonex®.
-
Subjects who suffer from any form of progressive MS
-
Any condition which the investigator feels may interfere with participation in the study
-
Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation
-
Subjects who received any investigational medication, immunosuppressives or cytotoxic agents within 6 months prior to screening
-
Previous treatment with immunomodulators within two months prior to screening
-
Pregnancy or breastfeeding
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Teva Investigational Site 1267 | Birmingham | Alabama | United States | 35209 |
2 | Teva Investigational Site 1237 | Phoenix | Arizona | United States | 85013 |
3 | Teva Investigational Site 1252 | Phoenix | Arizona | United States | 85018 |
4 | Teva Investigational Site 1279 | Phoenix | Arizona | United States | 85018 |
5 | Teva Investigational Site 1276 | Tucson | Arizona | United States | 85741-3537 |
6 | Teva Investigational Site 1272 | Pasadena | California | United States | 91105 |
7 | Teva Investigational Site 1238 | Sacramento | California | United States | 95817 |
8 | Teva Investigational Site 1280 | Aurora | Colorado | United States | 80045 |
9 | Teva Investigational Site 1255 | Orlando | Florida | United States | 32806 |
10 | Teva Investigational Site 1282 | Sarasota | Florida | United States | 34233 |
11 | Teva Investigational Site 1275 | Atlanta | Georgia | United States | 30309 |
12 | Teva Investigational Site 1250 | Peoria | Illinois | United States | 61603 |
13 | Teva Investigational Site 1260 | Indianapolis | Indiana | United States | 46202 |
14 | Teva Investigational Site 1268 | Lenexa | Kansas | United States | 66214 |
15 | Teva Investigational Site 1277 | New Orleans | Louisiana | United States | 70115 |
16 | Teva Investigational Site 1263 | Shreveport | Louisiana | United States | 71103 |
17 | Teva Investigational Site 1269 | Baltimore | Maryland | United States | 21201 |
18 | Teva Investigational Site 1274 | Grand Rapids | Michigan | United States | 49525 |
19 | Teva Investigational Site 1239 | Lebanon | New Hampshire | United States | 03766 |
20 | Teva Investigational Site 1265 | Teaneck | New Jersey | United States | 07666 |
21 | Teva Investigational Site 1273 | Albany | New York | United States | 12205 |
22 | Teva Investigational Site 1264 | Amherst | New York | United States | 14226 |
23 | Teva Investigational Site 1283 | Cedarhurst | New York | United States | 11516 |
24 | Teva Investigational Site 1249 | Raleigh | North Carolina | United States | 27607 |
25 | Teva Investigational Site 1262 | Winston-Salem | North Carolina | United States | 27103 |
26 | Teva Investigational Site 1261 | Akron | Ohio | United States | 44320 |
27 | Teva Investigational Site 1241 | Canton | Ohio | United States | 44718 |
28 | Teva Investigational Site 1245 | Cleveland | Ohio | United States | 44195-5244 |
29 | Teva Investigational Site 1247 | Columbus | Ohio | United States | 43221 |
30 | Teva Investigational Site 1244 | Portland | Oregon | United States | 97225 |
31 | Teva Investigational Site 1258 | Philadelphia | Pennsylvania | United States | 19107 |
32 | Teva Investigational Site 1281 | Nashville | Tennessee | United States | 37205 |
33 | Teva Investigational Site 1284 | San Antonio | Texas | United States | 78231 |
34 | Teva Investigational Site 1248 | Richmond | Virginia | United States | 23298-0599 |
35 | Teva Investigational Site 1270 | Roanoke | Virginia | United States | 24018 |
36 | Teva Investigational Site 1253 | Tacoma | Washington | United States | 98405 |
37 | Teva Investigational Site 5914 | Pleven | Bulgaria | 5800 | |
38 | Teva Investigational Site 5915 | Pleven | Bulgaria | 5800 | |
39 | Teva Investigational Site 5917 | Plovdiv | Bulgaria | 4000 | |
40 | Teva Investigational Site 4212 | Ruse | Bulgaria | 7000 | |
41 | Teva Investigational Site 5916 | Shumen | Bulgaria | 9700 | |
42 | Teva Investigational Site 5920 | Sofia | Bulgaria | 1000 | |
43 | Teva Investigational Site 5907 | Sofia | Bulgaria | 1113 | |
44 | Teva Investigational Site 5910 | Sofia | Bulgaria | 1113 | |
45 | Teva Investigational Site 5909 | Sofia | Bulgaria | 1309 | |
46 | Teva Investigational Site 5919 | Sofia | Bulgaria | 1407 | |
47 | Teva Investigational Site 5906 | Sofia | Bulgaria | 1606 | |
48 | Teva Investigational Site 5908 | Sofia | Bulgaria | 1606 | |
49 | Teva Investigational Site 5911 | Sofia | Bulgaria | 1606 | |
50 | Teva Investigational Site 5912 | Sofia | Bulgaria | 1606 | |
51 | Teva Investigational Site 5918 | Stara Zagora | Bulgaria | 6000 | |
52 | Teva Investigational Site 5913 | Varna | Bulgaria | 9010 | |
53 | Teva Investigational Site 4211 | Veliko Tarnovo | Bulgaria | 5000 | |
54 | Teva Investigational Site 6003 | Osijek | Croatia | 31 000 | |
55 | Teva Investigational Site 6004 | Split | Croatia | 21000 | |
56 | Teva Investigational Site 6005 | Varazdin | Croatia | 42000 | |
57 | Teva Investigational Site 6001 | Zagreb | Croatia | 10000 | |
58 | Teva Investigational Site 6002 | Zagreb | Croatia | 10000 | |
59 | Teva Investigational Site 6006 | Zagreb | Croatia | 10000 | |
60 | Teva Investigational Site 5422 | Brno | Czechia | 602 00 | |
61 | Teva Investigational Site 5419 | Olomouc | Czechia | 779 00 | |
62 | Teva Investigational Site 5418 | Praha 2 | Czechia | 128 08 | |
63 | Teva Investigational Site 5420 | Praha 5- Motol | Czechia | 150 06 | |
64 | Teva Investigational Site 5421 | Teplice | Czechia | 415 29 | |
65 | Teva Investigational Site 5508 | Kohtla-Jarve | Estonia | 31025 | |
66 | Teva Investigational Site 5507 | Tallinn | Estonia | EE-10617 | |
67 | Teva Investigational Site 5509 | Tartu | Estonia | EE-51014 | |
68 | Teva Investigational Site 8102 | Tbilisi | Georgia | 0112 | |
69 | Teva Investigational Site 8104 | Tbilisi | Georgia | 0112 | |
70 | Teva Investigational Site 8103 | Tbilisi | Georgia | 0179 | |
71 | Teva Investigational Site 6701 | Bayreuth | Germany | 95445 | |
72 | Teva Investigational Site 6703 | Berlin | Germany | 10117 | |
73 | Teva Investigational Site 6402 | Berlin | Germany | 12203 | |
74 | Teva Investigational Site 6700 | Berlin | Germany | 13088 | |
75 | Teva Investigational Site 6702 | Dresden | Germany | 01307 | |
76 | Teva Investigational Site 6401 | Hannover | Germany | 30559 | |
77 | Teva Investigational Site 6403 | Munster | Germany | 48149 | |
78 | Teva Investigational Site 6400 | Ulm | Germany | 89081 | |
79 | Teva Investigational Site 8043 | Haifa | Israel | 3436212 | |
80 | Teva Investigational Site 8041 | Jerusalem | Israel | 9112001 | |
81 | Teva Investigational Site 8040 | Ramat Gan | Israel | 5262160 | |
82 | Teva Investigational Site 8042 | Ramat Gan | Israel | 5262160 | |
83 | Teva Investigational Site 3056 | Bologna | Italy | 40139 | |
84 | Teva Investigational Site 3062 | Catania | Italy | 95122 | |
85 | Teva Investigational Site 3053 | Cefalu | Italy | 90015 | |
86 | Teva Investigational Site 3054 | Chieti | Italy | 66100 | |
87 | Teva Investigational Site 3061 | Empoli | Italy | 50053 | |
88 | Teva Investigational Site 3049 | Firenze | Italy | 50139 | |
89 | Teva Investigational Site 3055 | Napoli | Italy | 80131 | |
90 | Teva Investigational Site 3048 | Rome | Italy | 00133 | |
91 | Teva Investigational Site 3052 | Rome | Italy | 00149 | |
92 | Teva Investigational Site 3050 | Rome | Italy | 00168 | |
93 | Teva Investigational Site 3060 | Rome | Italy | 163 | |
94 | Teva Investigational Site 3051 | Torino | Italy | 10126 | |
95 | Teva Investigational Site 5708 | Kaunas | Lithuania | 50009 | |
96 | Teva Investigational Site 5707 | Siauliai | Lithuania | 76231 | |
97 | Teva Investigational Site 6502 | Bitola | North Macedonia | 7000 | |
98 | Teva Investigational Site 6500 | Skopje | North Macedonia | 1000 | |
99 | Teva Investigational Site 6501 | Skopje | North Macedonia | 1000 | |
100 | Teva Investigational Site 5337 | Bialystok | Poland | 15-402 | |
101 | Teva Investigational Site 5329 | Gdansk | Poland | 80-803 | |
102 | Teva Investigational Site 5338 | Gdansk | Poland | 80-952 | |
103 | Teva Investigational Site 6602 | Gorzow Wielkopolski | Poland | 66-400 | |
104 | Teva Investigational Site 5333 | Grodzisk Mazowiecki | Poland | 05-825 | |
105 | Teva Investigational Site 5339 | Katowice | Poland | 40-635 | |
106 | Teva Investigational Site 5334 | Katowice | Poland | 40-752 | |
107 | Teva Investigational Site 6603 | Kielce | Poland | 25-736 | |
108 | Teva Investigational Site 4213 | Konskie | Poland | 26-200 | |
109 | Teva Investigational Site 5332 | Koscierzyna | Poland | 83-400 | |
110 | Teva Investigational Site 5345 | Krakow | Poland | 31-826 | |
111 | Teva Investigational Site 5328 | Lodz | Poland | 90-153 | |
112 | Teva Investigational Site 5330 | Olsztyn | Poland | 10-560 | |
113 | Teva Investigational Site 5331 | Szczecin | Poland | 70-215 | |
114 | Teva Investigational Site 5336 | Warsaw | Poland | 02-957 | |
115 | Teva Investigational Site 5340 | Warszawa | Poland | 00-909 | |
116 | Teva Investigational Site 5341 | Warszawa | Poland | 02-097 | |
117 | Teva Investigational Site 5335 | Wroclaw | Poland | 50-556 | |
118 | Teva Investigational Site 1243 | Guaynabo | Puerto Rico | 00969 | |
119 | Teva Investigational Site 5218 | Bucharest | Romania | 010825 | |
120 | Teva Investigational Site 5214 | Bucuresti | Romania | 022328 | |
121 | Teva Investigational Site 5213 | Bucuresti | Romania | 050098 | |
122 | Teva Investigational Site 5215 | Cluj-Napoca | Romania | 400012 | |
123 | Teva Investigational Site 5217 | Constanta | Romania | 900591 | |
124 | Teva Investigational Site 8209 | Craiova | Romania | 200515 | |
125 | Teva Investigational Site 5216 | Iasi | Romania | 700661 | |
126 | Teva Investigational Site 5219 | Sibiu | Romania | 550245 | |
127 | Teva Investigational Site 5043 | Barnaul | Russian Federation | 656024 | |
128 | Teva Investigational Site 5033 | Moscow | Russian Federation | 117152 | |
129 | Teva Investigational Site 5032 | Moscow | Russian Federation | 117997 | |
130 | Teva Investigational Site 5041 | Moscow | Russian Federation | 125367 | |
131 | Teva Investigational Site 5038 | Novosibirsk | Russian Federation | 630087 | |
132 | Teva Investigational Site 5042 | Novosibirsk | Russian Federation | 630117 | |
133 | Teva Investigational Site 5035 | Saint Petersburg | Russian Federation | 197022 | |
134 | Teva Investigational Site 5037 | Samara | Russian Federation | 443095 | |
135 | Teva Investigational Site 5036 | St. Petersburg | Russian Federation | 194291 | |
136 | Teva Investigational Site 5034 | St. Petersburg | Russian Federation | 197376 | |
137 | Teva Investigational Site 5044 | Ufa | Russian Federation | 450007 | |
138 | Teva Investigational Site 6200 | Bratislava | Slovakia | 813 69 | |
139 | Teva Investigational Site 6201 | Bratislava | Slovakia | 826 06 | |
140 | Teva Investigational Site 6202 | Nitra | Slovakia | 949 01 | |
141 | Teva Investigational Site 6203 | Zilina | Slovakia | 010 01 | |
142 | Teva Investigational Site 9007 | Bloemfontein | South Africa | 9301 | |
143 | Teva Investigational Site 9001 | Cape Town | South Africa | 7925 | |
144 | Teva Investigational Site 9004 | Johannesburg | South Africa | 2157 | |
145 | Teva Investigational Site 9003 | Johannesburg | South Africa | 2193 | |
146 | Teva Investigational Site 9008 | Pietermaritzburg | South Africa | 3201 | |
147 | Teva Investigational Site 9005 | Pretoria | South Africa | 0041 | |
148 | Teva Investigational Site 9006 | Rosebank | South Africa | 2196 | |
149 | Teva Investigational Site 3147 | Barcelona | Spain | 08035 | |
150 | Teva Investigational Site 3154 | Figueres-Girona | Spain | 17600 | |
151 | Teva Investigational Site 3149 | L'Hospitalet de Llobregat | Spain | 08907 | |
152 | Teva Investigational Site 3152 | Madrid | Spain | 28041 | |
153 | Teva Investigational Site 3151 | Malaga | Spain | 29010 | |
154 | Teva Investigational Site 3148 | Sevilla | Spain | 41009 | |
155 | Teva Investigational Site 3153 | Tortosa-Tarragona | Spain | 43500 | |
156 | Teva Investigational Site 6503 | Chernihiv | Ukraine | 14029 | |
157 | Teva Investigational Site 5823 | Chernivtsi | Ukraine | 58018 | |
158 | Teva Investigational Site 5811 | Dnipropetrovsk | Ukraine | 49027 | |
159 | Teva Investigational Site 5812 | Donetsk | Ukraine | 83003 | |
160 | Teva Investigational Site 5814 | Ivano-Frankivsk | Ukraine | 76008 | |
161 | Teva Investigational Site 5817 | Kharkiv | Ukraine | 61018 | |
162 | Teva Investigational Site 5818 | Kharkiv | Ukraine | 61068 | |
163 | Teva Investigational Site 5815 | Kharkiv | Ukraine | 61103 | |
164 | Teva Investigational Site 5822 | Kyiv | Ukraine | 03110 | |
165 | Teva Investigational Site 5809 | Lviv | Ukraine | 79010 | |
166 | Teva Investigational Site 5820 | Odessa | Ukraine | 65025 | |
167 | Teva Investigational Site 5821 | Poltava | Ukraine | 36024 | |
168 | Teva Investigational Site 5810 | Vinnytsya | Ukraine | 21005 | |
169 | Teva Investigational Site 5819 | Zaporizhzhya | Ukraine | 69035 | |
170 | Teva Investigational Site 5816 | Zaporizhzhya | Ukraine | 69600 |
Sponsors and Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
Investigators
- Study Director: Teva Medical Expert, M.D., Teva Branded Pharmaceutical Products R&D, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MS-LAQ-302
- 2007-005450-23
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 millograms (mg) orally once daily for 24 months. | Participants received an injection of Avonex® 30 micrograms (mcg) given intramuscularly (IM) once weekly for 24 months. |
Period Title: Overall Study | |||
STARTED | 450 | 434 | 447 |
Received at Least 1 Dose of Study Drug | 449 | 433 | 442 |
COMPLETED | 359 | 353 | 378 |
NOT COMPLETED | 91 | 81 | 69 |
Baseline Characteristics
Arm/Group Title | Placebo | Laquinimod | Avonex® | Total |
---|---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. | Total of all reporting groups |
Overall Participants | 450 | 434 | 447 | 1331 |
Age (years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [years] |
37.5
(9.5)
|
37.0
(9.3)
|
38.2
(9.5)
|
37.6
(9.5)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
321
71.3%
|
282
65%
|
307
68.7%
|
910
68.4%
|
Male |
129
28.7%
|
152
35%
|
140
31.3%
|
421
31.6%
|
Race/Ethnicity, Customized (Count of Participants) | ||||
Asian |
0
0%
|
1
0.2%
|
1
0.2%
|
2
0.2%
|
Black of African Heritage |
1
0.2%
|
1
0.2%
|
0
0%
|
2
0.2%
|
Black/African American |
2
0.4%
|
1
0.2%
|
4
0.9%
|
7
0.5%
|
White |
443
98.4%
|
426
98.2%
|
440
98.4%
|
1309
98.3%
|
Hispanic |
3
0.7%
|
3
0.7%
|
1
0.2%
|
7
0.5%
|
Other |
1
0.2%
|
2
0.5%
|
1
0.2%
|
4
0.3%
|
Outcome Measures
Title | Annualized Rate of Confirmed Relapses |
---|---|
Description | A relapse was defined as the appearance of new neurological abnormalities or the reappearance of previously observed neurological abnormalities; lasting at least 48 hours and immediately preceded by an improved neurological state of ≥30 days from onset of previous relapse, accompanied by observed objective neurological changes (an increase of ≥0.5 in Expanded Disability Status Scale [EDSS] score, or an increase of 1 grade in the score of 2 or more of the 7 Functional Systems [FS], or an increase of 2 grades in the score of 1 FS as compared to the previous evaluation). Total number of confirmed relapses during the treatment period was divided by the sum of number of days on study in the treatment period and then multiplied by the number of days in the year to calculate the annualized relapse rate. Annualized relapse rate was derived from a baseline-adjusted negative binomial regression. |
Time Frame | Baseline up to Month 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 450 | 434 | 447 |
Mean (95% Confidence Interval) [relapse per year] |
0.344
|
0.283
|
0.255
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Placebo, Laquinimod |
---|---|---|
Comments | Analysis was performed using baseline-adjusted negative binomial regression, where a participant's number of relapses during the double-blind, placebo-controlled phase served as the response variable and an offset based on the log of participant's exposure in years was employed to adjust for variability of treatment exposure. The model included baseline EDSS score, log of (prior 2-year number of relapses+1) and CGR as covariates. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0746 |
Comments | Threshold for significance at 0.05 level. | |
Method | Negative Binomial Regression | |
Comments | ||
Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
Estimated Value | 0.823 | |
Confidence Interval |
(2-Sided) 95% 0.664 to 1.020 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.090 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Placebo, Avonex® |
---|---|---|
Comments | Analysis was performed using baseline-adjusted negative binomial regression, where a participant's number of relapses during the double-blind, placebo-controlled phase served as the response variable and an offset based on the log of participant's exposure in years was employed to adjust for variability of treatment exposure. The model included baseline EDSS score, log of (prior 2-year number of relapses+1) and CGR as covariates. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0067 |
Comments | ||
Method | Negative Binomial Regression | |
Comments | ||
Method of Estimation | Estimation Parameter | Risk Ratio (RR) |
Estimated Value | 0.741 | |
Confidence Interval |
(2-Sided) 95% 0.596 to 0.920 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.082 |
|
Estimation Comments |
Title | Change From Baseline in Disability as Assessed by the Multiple Sclerosis Functional Composite (MSFC) Score |
---|---|
Description | The Multiple Sclerosis Functional Composite is an instrument assessing disability that consists of 3 clinical assessments. The 3 are Timed 25-Foot Walk, 9-Hole Peg Test which measures upper extremity (arm and hand) function, and PASAT (Paced Auditory Serial Addition Test) which is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. A Z-score is used to define a common metric from the 3 assessments that constitute the MSFC score. The study's population at baseline was used as reference population for the Z-score calculation. A Z-score of 0 represents the population mean at baseline. Higher Z-scores correspond to an improved outcome. |
Time Frame | Baseline, Month 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 358 | 351 | 377 |
Mean (Standard Deviation) [Z score] |
-0.5
(0.85)
|
-0.00
(0.85)
|
-0.01
(0.75)
|
Title | Percent Change From Baseline in Brain Volume |
---|---|
Description | Change in brain volume was derived from MRI scans obtained at baseline and at Month 24. |
Time Frame | Baseline, Month 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 341 | 332 | 361 |
Mean (Standard Deviation) [Percent Change] |
-0.53
(0.65)
|
-0.51
(0.65)
|
-0.53
(0.65)
|
Title | Accumulation of Physical Disability Measured by the Number of Participants With Confirmed Progression of EDSS |
---|---|
Description | A confirmed progression of EDSS was defined as a 1 point increase from baseline on EDSS score if baseline EDSS was between 0 and 5.0, or a 0.5 point increase if baseline EDSS was 5.5, confirmed 3 months later. 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 confirmed progression (number of participants with confirmed progression of EDSS) sustained for 3 months. Progression could not be confirmed during a relapse. |
Time Frame | Baseline up to Month 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 450 | 434 | 447 |
Count of Participants [Participants] |
60
13.3%
|
42
9.7%
|
47
10.5%
|
Title | Change From Baseline in General Health Status as Assessed by the Short-Form General Health Survey (SF-36) Patient-Reported Questionnaire For Physical Component Summary (PCS) Scores |
---|---|
Description | The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Items 1 to 4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item were summed and averaged (range: 0=worst to 100=best). Higher scores represent better health status and functional ability. |
Time Frame | Baseline, Month 6, Month 12, Month 18, Month 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 450 | 434 | 447 |
Month 6 |
-0.2
(6.3)
|
0.1
(6.3)
|
-0.1
(6.3)
|
Month 12 |
-0.3
(6.9)
|
-0.1
(6.9)
|
0.0
(6.7)
|
Month 18 |
-0.5
(7.0)
|
-0.3
(7.0)
|
0.2
(6.9)
|
Month 24 |
-0.6
(7.6)
|
0.1
(6.9)
|
0.2
(7.0)
|
Title | Change From Baseline in General Health Status as Assessed by the Short-Form General Health Survey (SF-36) Patient-Reported Questionnaire For Mental Component Summary (MCS) Scores |
---|---|
Description | The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Items 1 to 4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item were summed and averaged (range: 0=worst to 100=best). Higher scores represent better health status and functional ability. |
Time Frame | Baseline, Month 6, Month 12, Month 18, Month 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 450 | 434 | 447 |
Month 6 |
-0.4
(8.5)
|
-0.6
(8.2)
|
-0.4
(8.9)
|
Month 12 |
-0.7
(9.2)
|
-0.1
(9.8)
|
-0.5
(9.0)
|
Month 18 |
-0.9
(9.3)
|
-1.4
(10.4)
|
-0.7
(9.2)
|
Month 24 |
-0.5
(9.2)
|
-0.9
(9.6)
|
-0.3
(9.3)
|
Title | Cumulative Number of New or Enlarging Hypointense Lesions on Enhanced T1 Scans |
---|---|
Description | The cumulative number of new or enlarging hypointense lesions was calculated as the sum of the numbers of new or enlarging hypointense lesions observed on scans taken at Months 12 and 24. |
Time Frame | Months 12 and 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 393 | 381 | 403 |
Mean (Standard Deviation) [lesions] |
7.10
(10.25)
|
7.33
(10.87)
|
5.91
(8.58)
|
Title | Cumulative Number of Enhancing Lesions on T1-Weighted Images |
---|---|
Description | The cumulative number of T1 Gadolinium (Gd)-enhancing lesions was calculated as the sum of the numbers of Gd-enhancing lesions observed on scans taken at Months 12 and 24. |
Time Frame | Months 12 and 24 |
Outcome Measure Data
Analysis Population Description |
---|
ITT analysis set included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. |
Arm/Group Title | Placebo | Laquinimod | Avonex® |
---|---|---|---|
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. |
Measure Participants | 393 | 381 | 404 |
Mean (Standard Deviation) [lesions] |
2.70
(8.00)
|
2.58
(7.40)
|
1.23
(3.32)
|
Adverse Events
Time Frame | Baseline up to Month 24 | |||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | Safety analysis set included all randomized participants who received at least 1 dose of laquinimod. | |||||
Arm/Group Title | Placebo | Laquinimod | Avonex® | |||
Arm/Group Description | Participants received 1 capsule of placebo matched to laquinimod orally once daily for 24 months. | Participants received 1 capsule of laquinimod 0.6 mg orally once daily for 24 months. | Participants received an injection of Avonex® 30 mcg given IM once weekly for 24 months. | |||
All Cause Mortality |
||||||
Placebo | Laquinimod | Avonex® | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/449 (0%) | 1/433 (0.2%) | 1/442 (0.2%) | |||
Serious Adverse Events |
||||||
Placebo | Laquinimod | Avonex® | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 36/449 (8%) | 31/433 (7.2%) | 25/442 (5.7%) | |||
Blood and lymphatic system disorders | ||||||
Anaemia | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Iron deficiency anaemia | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Lymphadenitis | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Cardiac disorders | ||||||
Acute myocardial infarction | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 2/442 (0.5%) | 2 |
Cardiopulmonary failure | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Myocardial ischaemia | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Palpitations | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Supraventricular tachycardia | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Ear and labyrinth disorders | ||||||
Vertigo positional | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Gastrointestinal disorders | ||||||
Abdominal pain | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Abdominal pain upper | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Gastric perforation | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Gastritis | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
General disorders | ||||||
Chest pain | 0/449 (0%) | 0 | 2/433 (0.5%) | 2 | 1/442 (0.2%) | 1 |
Hepatobiliary disorders | ||||||
Cholelithiasis | 1/449 (0.2%) | 1 | 1/433 (0.2%) | 1 | 1/442 (0.2%) | 1 |
Infections and infestations | ||||||
Acute tonsillitis | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Appendicitis | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Bronchopneumonia | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Cellulitis | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Diverticulitis | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Influenza | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Injection site abscess | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Measles | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Pharyngitis | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Pneumonia | 1/449 (0.2%) | 1 | 1/433 (0.2%) | 1 | 1/442 (0.2%) | 1 |
Pneumonia bacterial | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Pneumonia measles | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Pulmonary tuberculosis | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 1/442 (0.2%) | 1 |
Pyelonephritis acute | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Respiratory tract infection | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Secondary syphilis | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Sepsis | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Upper respiratory tract infection | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Urinary tract infection | 1/449 (0.2%) | 1 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Viral infection | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||
Ankle fracture | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Clavicle fracture | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Femur fracture | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Jaw fracture | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Limb injury | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Road traffic accident | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Investigations | ||||||
Blood creatine phosphokinase increased | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Hepatic enzyme increased | 2/449 (0.4%) | 2 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||
Intervertebral disc protrusion | 2/449 (0.4%) | 2 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Muscular weakness | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Osteoarthritis | 0/449 (0%) | 0 | 2/433 (0.5%) | 2 | 0/442 (0%) | 0 |
Osteochondrosis | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Angiomyolipoma | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Fibroadenoma of breast | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Thyroid cancer | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 1/442 (0.2%) | 1 |
Uterine leiomyoma | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Nervous system disorders | ||||||
Cerebrovascular accident | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Cervicobrachial syndrome | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Headache | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Ischaemic stroke | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Migraine | 2/449 (0.4%) | 2 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Multiple sclerosis relapse | 2/449 (0.4%) | 2 | 3/433 (0.7%) | 3 | 0/442 (0%) | 0 |
Myelitis | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Neurological decompensation | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Paraesthesia | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Radiculopathy | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Reversible ischaemic neurological deficit | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Sciatica | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Trigeminal neuralgia | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Pregnancy, puerperium and perinatal conditions | ||||||
Abortion spontaneous | 1/449 (0.2%) | 1 | 1/433 (0.2%) | 1 | 1/442 (0.2%) | 1 |
Abortion threatened | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Psychiatric disorders | ||||||
Depression | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 1/442 (0.2%) | 1 |
Depression suicidal | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Mania | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Renal and urinary disorders | ||||||
Nephrolithiasis | 2/449 (0.4%) | 2 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Renal colic | 2/449 (0.4%) | 2 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Reproductive system and breast disorders | ||||||
Cervical dysplasia | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Dysmenorrhoea | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Endometrial hyperplasia | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Ovarian cyst | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Sperm granuloma | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Uterine haemorrhage | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||
Paranasal cyst | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Pleural effusion | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Pneumomediastinum | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Pneumothorax | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||
Angioedema | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Dermal cyst | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Erythema nodosum | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Surgical and medical procedures | ||||||
Acoustic neuroma removal | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Colectomy | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Hysterectomy | 2/449 (0.4%) | 2 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Internal fixation of spine | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Intervertebral disc operation | 1/449 (0.2%) | 1 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Lymphadenectomy | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Meniscus removal | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Nasal septal operation | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Orchidectomy | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Radical hysterectomy | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Spinal cord operation | 0/449 (0%) | 0 | 1/433 (0.2%) | 1 | 0/442 (0%) | 0 |
Thyroidectomy | 0/449 (0%) | 0 | 0/433 (0%) | 0 | 1/442 (0.2%) | 1 |
Tonsillectomy | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Vascular disorders | ||||||
Deep vein thrombosis | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 2/442 (0.5%) | 3 |
Hypotension | 1/449 (0.2%) | 1 | 0/433 (0%) | 0 | 0/442 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
Placebo | Laquinimod | Avonex® | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 146/449 (32.5%) | 158/433 (36.5%) | 286/442 (64.7%) | |||
General disorders | ||||||
Influenza like illness | 7/449 (1.6%) | 7 | 5/433 (1.2%) | 5 | 206/442 (46.6%) | 385 |
Pyrexia | 7/449 (1.6%) | 10 | 6/433 (1.4%) | 7 | 52/442 (11.8%) | 77 |
Infections and infestations | ||||||
Influenza | 28/449 (6.2%) | 32 | 27/433 (6.2%) | 30 | 20/442 (4.5%) | 30 |
Nasopharyngitis | 35/449 (7.8%) | 45 | 40/433 (9.2%) | 63 | 29/442 (6.6%) | 37 |
Upper respiratory tract infection | 36/449 (8%) | 43 | 34/433 (7.9%) | 41 | 22/442 (5%) | 27 |
Musculoskeletal and connective tissue disorders | ||||||
Arthralgia | 18/449 (4%) | 26 | 24/433 (5.5%) | 27 | 18/442 (4.1%) | 21 |
Back pain | 32/449 (7.1%) | 50 | 44/433 (10.2%) | 61 | 15/442 (3.4%) | 30 |
Nervous system disorders | ||||||
Headache | 53/449 (11.8%) | 105 | 54/433 (12.5%) | 100 | 60/442 (13.6%) | 99 |
Limitations/Caveats
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 | 1-888-483-8279 |
USMedInfo@tevapharm.com |
- MS-LAQ-302
- 2007-005450-23