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

Relapsing Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01047319
• Other study ID #: MS-LAQ-302E
• Secondary ID: 2009-015815-42
• Status: Terminated
• Phase: Phase 3
• Start date: May 27, 2010
• Est. completion date: June 30, 2017

Study information

• Verified date: December 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1047
• Est. completion date: June 30, 2017
• Est. primary completion date: June 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

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

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

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

4. Subjects must be able to comprehend, sign and date a written informed consent prior to entering the MS-LAQ-302E study.

Exclusion Criteria:

1. Premature discontinuation from the MS-LAQ-302 study, for any reason.

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

3. Subjects with clinically significant or unstable medical or surgical condition detected or worsened during the MS-LAQ-302 study, which preclude safe participation and completion of the MS-LAQ-302E study. Acute exacerbation of MS will not exclude participation in the MS-LAQ-302E study.

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

Related Conditions & MeSH terms

• Disease Progression
• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Laquinimod
One capsule containing 0.6 mg laquinimod to be administered orally once daily.

Locations

Country	Name	City	State
Bulgaria	Teva Investigational Site 5914	Pleven
Bulgaria	Teva Investigational Site 5915	Pleven
Bulgaria	Teva Investigational Site 5917	Plovdiv
Bulgaria	Teva Investigational Site 4212	Ruse
Bulgaria	Teva Investigational Site 5916	Shumen
Bulgaria	Teva Investigational Site 5906	Sofia
Bulgaria	Teva Investigational Site 5907	Sofia
Bulgaria	Teva Investigational Site 5908	Sofia
Bulgaria	Teva Investigational Site 5909	Sofia
Bulgaria	Teva Investigational Site 5910	Sofia
Bulgaria	Teva Investigational Site 5911	Sofia
Bulgaria	Teva Investigational Site 5912	Sofia
Bulgaria	Teva Investigational Site 5919	Sofia
Bulgaria	Teva Investigational Site 5920	Sofia
Bulgaria	Teva Investigational Site 5918	Stara Zagora
Bulgaria	Teva Investigational Site 5913	Varna
Bulgaria	Teva Investigational Site 4211	Veliko Tarnovo
Croatia	Teva Investigational Site 6003	Osijek
Croatia	Teva Investigational Site 6005	Varazdin
Croatia	Teva Investigational Site 6001	Zagreb
Croatia	Teva Investigational Site 6002	Zagreb
Croatia	Teva Investigational Site 6006	Zagreb
Czechia	Teva Investigational Site 5419	Olomouc
Czechia	Teva Investigational Site 5418	Praha 2
Czechia	Teva Investigational Site 5420	Praha 5- Motol
Czechia	Teva Investigational Site 5421	Teplice
Estonia	Teva Investigational Site 5508	Kohtla-Jarve
Estonia	Teva Investigational Site 5507	Tallinn
Estonia	Teva Investigational Site 5509	Tartu
Georgia	Teva Investigational Site 8102	Tbilisi
Georgia	Teva Investigational Site 8103	Tbilisi
Georgia	Teva Investigational Site 8104	Tbilisi
Germany	Teva Investigational Site 6402	Berlin
Germany	Teva Investigational Site 6703	Berlin
Germany	Teva Investigational Site 6400	Ulm
Israel	Teva Investigational Site 8041	Jerusalem
Israel	Teva Investigational Site 8040	Ramat Gan
Italy	Teva Investigational Site 3056	Bologna
Italy	Teva Investigational Site 3053	Cefalu
Italy	Teva Investigational Site 3054	Chieti
Italy	Teva Investigational Site 3061	Empoli
Italy	Teva Investigational Site 3049	Firenze
Italy	Teva Investigational Site 3055	Napoli
Italy	Teva Investigational Site 3048	Rome
Italy	Teva Investigational Site 3050	Rome
Italy	Teva Investigational Site 3052	Rome
Lithuania	Teva Investigational Site 5708	Kaunas
Lithuania	Teva Investigational Site 5707	Siauliai
North Macedonia	Teva Investigational Site 6500	Skopje
North Macedonia	Teva Investigational Site 6501	Skopje
North Macedonia	Teva Investigational Site 6502	Skopje
Poland	Teva Investigational Site 5337	Bialystok
Poland	Teva Investigational Site 5329	Gdansk
Poland	Teva Investigational Site 5338	Gdansk
Poland	Teva Investigational Site 6602	Gorzow Wielkopolski
Poland	Teva Investigational Site 5333	Grodzisk Mazowiecki
Poland	Teva Investigational Site 5334	Katowice
Poland	Teva Investigational Site 5339	Katowice
Poland	Teva Investigational Site 6603	Kielce
Poland	Teva Investigational Site 4213	Konskie
Poland	Teva Investigational Site 5332	Koscierzyna
Poland	Teva Investigational Site 5345	Krakow
Poland	Teva Investigational Site 5328	Lodz
Poland	Teva Investigational Site 5330	Olsztyn
Poland	Teva Investigational Site 5331	Szczecin
Poland	Teva Investigational Site 5336	Warsaw
Poland	Teva Investigational Site 5340	Warszawa
Poland	Teva Investigational Site 5341	Warszawa
Poland	Teva Investigational Site 5335	Wroclaw
Romania	Teva Investigational Site 5235	Balotesti
Romania	Teva Investigational Site 5218	Bucharest
Romania	Teva Investigational Site 5213	Bucuresti
Romania	Teva Investigational Site 5214	Bucuresti
Romania	Teva Investigational Site 5215	Cluj-Napoca
Romania	Teva Investigational Site 5217	Constanta
Romania	Teva Investigational Site 8209	Craiova
Romania	Teva Investigational Site 5216	Iasi
Romania	Teva Investigational Site 5219	Sibiu
Russian Federation	Teva Investigational Site 5043	Barnaul
Russian Federation	Teva Investigational Site 5032	Moscow
Russian Federation	Teva Investigational Site 5033	Moscow
Russian Federation	Teva Investigational Site 5041	Moscow
Russian Federation	Teva Investigational Site 5038	Novosibirsk
Russian Federation	Teva Investigational Site 5042	Novosibirsk
Russian Federation	Teva Investigational Site 5035	Saint Petersburg
Russian Federation	Teva Investigational Site 5037	Samara
Russian Federation	Teva Investigational Site 5034	St. Petersburg
Russian Federation	Teva Investigational Site 5036	St. Petersburg
Russian Federation	Teva Investigational Site 5044	Ufa
Slovakia	Teva Investigational Site 6200	Bratislava
Slovakia	Teva Investigational Site 6201	Bratislava
Slovakia	Teva Investigational Site 6202	Nitra
Slovakia	Teva Investigational Site 6203	Zilina
South Africa	Teva Investigational Site 9007	Bloemfontein
South Africa	Teva Investigational Site 9001	Cape Town
South Africa	Teva Investigational Site 9004	Johannesburg
South Africa	Teva Investigational Site 9003	Parktown- Johannesburg
South Africa	Teva Investigational Site 9008	Pietermaritzburg
South Africa	Teva Investigational Site 9005	Pretoria
South Africa	Teva Investigational Site 9006	Rosebank
Spain	Teva Investigational Site 3147	Barcelona
Spain	Teva Investigational Site 3154	Figueres-Girona
Spain	Teva Investigational Site 3149	L'Hospitalet de Llobregat
Spain	Teva Investigational Site 3152	Madrid
Spain	Teva Investigational Site 3151	Malaga
Spain	Teva Investigational Site 3148	Sevilla
Spain	Teva Investigational Site 3153	Tortosa-Tarragona
Ukraine	Teva Investigational Site 6503	Chernihiv
Ukraine	Teva Investigational Site 5823	Chernivtsi
Ukraine	Teva Investigational Site 5811	Dnipropetrovsk
Ukraine	Teva Investigational Site 5812	Donetsk
Ukraine	Teva Investigational Site 5814	Ivano-Frankivsk
Ukraine	Teva Investigational Site 5815	Kharkiv
Ukraine	Teva Investigational Site 5817	Kharkiv
Ukraine	Teva Investigational Site 5818	Kharkiv
Ukraine	Teva Investigational Site 5822	Kyiv
Ukraine	Teva Investigational Site 5809	Lviv
Ukraine	Teva Investigational Site 5820	Odessa
Ukraine	Teva Investigational Site 5821	Poltava
Ukraine	Teva Investigational Site 5810	Vinnytsya
Ukraine	Teva Investigational Site 5816	Zaporizhzhya
Ukraine	Teva Investigational Site 5819	Zaporizhzhya
United States	Teva Investigational Site 1261	Akron	Ohio
United States	Teva Investigational Site 1273	Albany	New York
United States	Teva Investigational Site 1264	Amherst	New York
United States	Teva Investigational Site 1275	Atlanta	Georgia
United States	Teva Investigational Site 1280	Aurora	Colorado
United States	Teva Investigational Site 1269	Baltimore	Maryland
United States	Teva Investigational Site 1245	Cleveland	Ohio
United States	Teva Investigational Site 1247	Columbus	Ohio
United States	Teva Investigational Site 1267	Homewood	Alabama
United States	Teva Investigational Site 1260	Indianapolis	Indiana
United States	Teva Investigational Site 1281	Nashville	Tennessee
United States	Teva Investigational Site 1272	Pasadena	California
United States	Teva Investigational Site 1250	Peoria	Illinois
United States	Teva Investigational Site 1237	Phoenix	Arizona
United States	Teva Investigational Site 1279	Phoenix	Arizona
United States	Teva Investigational Site 1244	Portland	Oregon
United States	Teva Investigational Site 1270	Roanoke	Virginia
United States	Teva Investigational Site 1238	Sacramento	California
United States	Teva Investigational Site 1282	Sarasota	Florida
United States	Teva Investigational Site 1263	Shreveport	Louisiana
United States	Teva Investigational Site 1253	Tacoma	Washington
United States	Teva Investigational Site 1276	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Bulgaria,  Croatia,  Czechia,  Estonia,  Georgia,  Germany,  Israel,  Italy,  Lithuania,  North Macedonia,  Poland,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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