Clinical trial NCT00745615: An Extension Study of LAQ/5062 Exploring the Long Term Safety, Tolerability and Clinical Effect Parameters During the Disease
Official title: An Active Extension of LAQ/5062 Study. A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Safety, Tolerability and Efficacy of Two Doses (0.3 mg and 0.6 mg) of Laquinimod, Orally Administered in Relapsing Remitting (R-R) Multiple Sclerosis (MS) Subjects (Study LAQ/5063 Active Double-Blind Phase) Followed by an Open Label Phase of Laquinimod 0.6 mg Daily (LAQ/5063 OL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Relapsing Remitting Multiple Sclerosis
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2008-09-03
Enrollment: 257
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multinational, multicenter, randomized, double-blind, parallel-group active extension of LAQ/5062 study (NCT00349193), assessing the tolerability, safety and efficacy of two doses (0.3 mg and 0.6 mg) of laquinimod, orally administered in participants with relapsing remitting multiple sclerosis (RRMS), followed by an open-label phase of laquinimod 0.6 mg daily. This study is LAQ/5063 (i.e., double-blind extension) and LAQ/5063 OL (i.e., subsequent open-label extension). - The first period of the extension study is an active, double-blind period. Participants from the active treatment arms in LAQ/5062 continue their assigned treatment in blinded fashion. Participants who were assigned to placebo treatment in LAQ/5062 are equally randomized in blinded-fashion to laquinimod 0.6 mg or laquinimod 0.3 mg. - Once termination visit of LAQ/5063 active double-blind phase (completion of the full 36 weeks or as requested by the Sponsor) is performed, all participants continue on laquinimod 0.6 mg daily as an open-label intervention. The open-label period continues as long as the Sponsor continues the development of laquinimod 0.6 mg for RRMS or early discontinuation.


Eligibility criteria: Inclusion Criteria - Participants must have completed the 36 weeks of treatment (completion of the full 36 weeks or as requested by the Sponsor) of the active double-blind phase. - Women of childbearing potential (for example, women who were not postmenopausal or surgically sterilized) must have practiced 2 acceptable methods of birth control for the duration of the study and until 30 days after the last dose of study medication (acceptable methods of birth control in this open-label extension phase included intrauterine devices, barrier methods \[condom or diaphragm with spermicide\], and hormonal methods of birth control \[for example, oral contraceptive, contraceptive patch, and long-acting injectable contraceptive\]). - Participants must have been willing and able to comply with the protocol requirements for the duration of LAQ/5063 OL. - Participants must have given signed, written informed consent prior to entering LAQ/5063 OL. - For the 36 months further extension: Participants must have completed the 24 months of treatment of the first period of the open label phase. Exclusion Criteria - For the 36 month further extension: Premature discontinuation from LAQ/5063 OL phase prior to completion of 24 months of treatment period. - Pregnancy or breastfeeding. - Participants with clinically significant or unstable medical or surgical condition, detected or worsened during the active double-blind phase of LAQ/5063, which would have precluded safe and complete study participation. - Use of experimental drugs, immunosuppressive drugs, and/or participation in clinical studies within the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Previous treatment with immunomodulators with the exception of laquinimod (including interferon \[IFN\] 1a and 1b, glatiramer acetate, and intravenous \[IV\] immunoglobulin) within 2 months prior to entering the open-label phase for those subjects who had a time gap between termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of corticosteroids within 30 days prior to entering the open-label phase, except for IV methylprednisolone 1 grams/day for a maximum of 3 days, in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of potent inhibitors of cytochrome P3A4 (CYP3A4) within 2 weeks prior to LAQ/5063 OL and/or use of fluoxetine 1 month prior to entering LAQ/5063 OL, in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of the following substrates of cytochrome P1A2 (CYP1A2): theophylline and/or warfarin within 2 weeks prior to entering LAQ/5063 OL, in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of amiodarone in the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Following the switch to new formulation (capsules), hypersensitivity to mannitol, meglumine, or sodium stearyl fumarate.

Primary outcomes:
measure: Double-Blind Extension Period: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline (Week 0) to Week 36
measure: Open-label Extension Period: Number of Participants With AEs
timeFrame: Baseline (Month 0/termination visit of double-blind extension phase [completion of full 36 weeks] until termination (as long as the Sponsor continued the development of laquinimod 0.6 mg for RRMS) or early discontinuation (up to approximately 10.5 years)
measure: Double-Blind Period: Number of Participants Who Prematurely Discontinued From the Study Due to Any Reason and Due to AEs
timeFrame: Baseline (Week 0) to Week 36
measure: Open-Label Period: Number of Participants Who Prematurely Discontinued From the Study Due to Any Reason and Due to AEs
timeFrame: Baseline (Month 0/termination visit of double-blind extension phase [completion of full 36 weeks] until termination (as long as the Sponsor continued the development of laquinimod 0.6 mg for RRMS) or early discontinuation (up to approximately 10.5 years)
Secondary outcomes:
measure: Double-Blind Period: Relapse Rate: Total Number of Confirmed Relapses
timeFrame: Baseline (Week 0) up to end of active double-blind phase or termination/early termination visit (up to Week 36)
measure: Double-Blind Period: Percentage of Relapse-Free Participants
timeFrame: Baseline (Week 0) up to end of active double-blind phase or termination/early termination visit (up to Week 36)
measure: Double-Blind Period: Number of Enhancing Lesions on T1-Weighted Images
timeFrame: At the end of active double-blind phase or termination/early termination visit (up to Week 36)
measure: Double-Blind Period: Number of New T2 Lesions
timeFrame: At the end of active double-blind phase or termination/early termination visit (up to Week 36)
measure: Double-Blind Period: Volume of T2 Lesions
timeFrame: At the end of active double-blind phase or termination/early termination visit (up to Week 36)
measure: Double-Blind Period: Number of New Hypointense T1 Lesion on Enhanced T1 Scans
timeFrame: At the end of active double-blind phase or termination/early termination visit (up to Week 36)
measure: Double-Blind Period: Kurtzke's Expanded Disability Status Scale (EDSS) Score
timeFrame: At the end of active double-blind phase or termination/early termination visit (up to Week 36)
Other outcomes:
Locations:
city: Hradec Kralove 3
country: Czechia
facility: Teva Investigational Site 382
city: Praha 2
country: Czechia
facility: Teva Investigational Site 380
city: Praha 5- Motol
country: Czechia
facility: Teva Investigational Site 384
city: Berlin
country: Germany
facility: Teva Investigational Site 681
city: Erfurt
country: Germany
facility: Teva Investigational Site 684
city: Hamburg
country: Germany
facility: Teva Investigational Site 687
city: Mainz
country: Germany
facility: Teva Investigational Site 683
city: Ulm
country: Germany
facility: Teva Investigational Site 686
city: Wuerzburg
country: Germany
facility: Teva Investigational Site 685
city: Debrecen
country: Hungary
facility: Teva Investigational Site 580
city: Gyula
country: Hungary
facility: Teva Investigational Site 581
city: Miskolc
country: Hungary
facility: Teva Investigational Site 583
city: Veszprem
country: Hungary
facility: Teva Investigational Site 584
city: Ramat -Gan
country: Israel
facility: Teva Investigational Site 981
state: IL
city: Haifa
country: Israel
facility: Teva Investigational Site 982
city: Jerusalem
country: Israel
facility: Teva Investigational Site 980
city: Cagliari
country: Italy
facility: Teva Investigational Site 483
city: Milano
country: Italy
facility: Teva Investigational Site 484
city: Milano
country: Italy
facility: Teva Investigational Site 486
city: Siena
country: Italy
facility: Teva Investigational Site 488
city: Bydgoszcz
country: Poland
facility: Teva Investigational Site 281
city: Katowice
country: Poland
facility: Teva Investigational Site 280
city: Katowice
country: Poland
facility: Teva Investigational Site 285
city: Lodz
country: Poland
facility: Teva Investigational Site 283
city: Lublin
country: Poland
facility: Teva Investigational Site 284
city: Wroclaw
country: Poland
facility: Teva Investigational Site 282
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 186
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 187
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 188
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 189
city: Saint Petersburg
country: Russian Federation
facility: Teva Investigational Site 180
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 181
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 182
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 184
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 185
city: Barakaldo
country: Spain
facility: Teva Investigational Site 782
city: Barcelona
country: Spain
facility: Teva Investigational Site 785
city: Bilbao
country: Spain
facility: Teva Investigational Site 781
city: L'Hospitalet de Llobregat
country: Spain
facility: Teva Investigational Site 784
city: Madrid
country: Spain
facility: Teva Investigational Site 780
city: Sevilla
country: Spain
facility: Teva Investigational Site 783
city: Liverpool
country: United Kingdom
facility: Teva Investigational Site 884
city: London
country: United Kingdom
facility: Teva Investigational Site 882
city: Sheffield
country: United Kingdom
facility: Teva Investigational Site 881
city: Stoke on Trent
country: United Kingdom
facility: Teva Investigational Site 883
Study officials:
affiliation: Instituto Scientifico Fondazione Centro S. Raffaele, Milan, Italy
name: Giancarlo Comi
role: PRINCIPAL_INVESTIGATOR
References: