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

Study Overview
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Brief Summary
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To make laquinimod 0.6 mg available for all subjects who completed the placebo-controlled MS-LAQ-302 study according to the protocol and to evaluate the long-term safety, tolerability and effect on disease course of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis.

Official Title
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A Multinational, Multicenter, Open-label, Single-assignment Extension of the MS-LAQ-302 (BRAVO) Study, to Evaluate the Long-term Safety, Tolerability and Effect on Disease Course of Daily Oral Laquinimod 0.6 mg in Subjects With Relapsing Multiple Sclerosis

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: Laquinimod


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have completed the Termination visit of MS-LAQ-302 (completion of all Termination visit activities) according to the MS-LAQ-302 protocol. Women of child-bearing potential must practice an acceptable method of birth control [acceptable methods of birth control in this open label extension phase include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch (or hormone-releasing vaginal ring), long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide)] during the study and up to 30 days after the last dose of the study drug.. Subjects must be willing and able to comply with the protocol requirements for the duration of the study. Subjects must be able to comprehend, sign and date a written informed consent prior to entering the MS-LAQ-302E study. Exclusion Criteria: Premature discontinuation from the MS-LAQ-302 study, for any reason. Pregnancy [according to urine dipstick β-HCG test performed at Baseline (Month 0E) visit] or breastfeeding. Subjects with clinically significant or unstable medical or surgical condition detected or worsened during the MS-LAQ-302 study, which preclude safe participation and completion of the MS-LAQ-302E study. Acute exacerbation of MS will not exclude participation in the MS-LAQ-302E study. Use of inhibitors of CYP3A4 within 2 weeks prior to baseline visit (V0E, Month 0E).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Laquinimod<br>One capsule containing 0.6 mg laquinimod to be administered orally once daily. | Drug: Laquinimod<br>* One capsule containing 0.6 mg laquinimod to be administered orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Treatment-Emergent Adverse Events (TEAEs) | A treatment-emergent adverse event was defined as any untoward medical occurrence that develops or worsens in severity following start of treatment and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs (SAE) include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. TEAEs associated with cancer, ischemic heart disease, cerebrovascular events, and arthritis were considered to be of special interest. | Day 1 up to 7.13 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Potentially Clinically Significant Abnormal Vital Signs | Vital signs with potentially clinically significant abnormal results were evaluated using the following significance criteria: Pulse rate: >=120 and increase >=30 beats/minute Systolic blood pressure low: <=90 and decrease >=30 mmHg Systolic blood pressure high: >=180 and increase >=30 mmHg Diastolic blood pressure low: <=50 and decrease >=20 mmHg Diastolic blood pressure high: >=100 and increase >=20 mmHg Note that the change is compared to baseline, | Baseline (Day 0 for extension), Day 1 up to 7.13 years | 
| Participants With Serum Chemistry Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study | Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non-PCS value are included in the population count. ALT=alanine aminotransferase ALP=alkaline phosphatase P-amylase=amylase, pancreatic AST=aspartate aminotransferase CRP=C reactive protein CK=creatine kinase CTN=creatinine FIB=fibrinogen GGT=gamma glutamyl transferase K=potassium | Baseline (Day 0), Day 1 to 7.13 years | 
| Participants With Serum Hematology Laboratory Tests That Were Potentially Clinically Significant (PCS) Abnormal Comparing Baseline to Any Time During the Study | Counts include two conditions: a change from High / Non-PCS at baseline to Low PCS at any point during the study a change from Low / Non-PCS at baseline to High PCS at any point during the study Participants whose condition was not changed from baseline or was changed to a non-PCS value are included in the population count. | Baseline (Day 0), Day 1 to 7.13 years | 
| Participants With Electrocardiogram (ECG) Fiindings That Shifted From Baseline to Any Time During the Study | Shifts are presented as Baseline finding / Worse finding at anytime during the study. Categories for findings are: normal abnormal, not clinically significant (Not CS) abnormal, clinically significant (CS) | Baseline (Day 0), Day 1 to 7.13 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing Multiple Sclerosis