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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00235755




Registration number
NCT00235755
Ethics application status
Date submitted
6/10/2005
Date registered
10/10/2005
Date last updated
21/04/2017

Titles & IDs
Public title
Retigabine Efficacy and Safety Trial for Partial Onset Refractory Seizures in Epilepsy
Scientific title
Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase 3 Study - Determine Efficacy and Safety of Two Doses of Retigabine (900 Mg/Day and 600 Mg/Day) Used as Adjunctive Therapy in Refractory Epilepsy Patients With Partial-Onset Seizures
Secondary ID [1] 0 0
VRX-RET-E22-302
Universal Trial Number (UTN)
Trial acronym
RESTORE2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Seizures 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Retigabine
Treatment: Drugs - Retigabine
Treatment: Drugs - Placebo

Placebo comparator: Placebo -

Experimental: Retigabine 600 mg -

Experimental: Retigabine 900 mg -


Treatment: Drugs: Retigabine
Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 3, patients will enter a 12 week maintenance phase.

Treatment: Drugs: Retigabine
Oral tablet. The starting daily dose will be 300 mg/day administered orally in three equally divided doses. This dosage will be increased by 150 mg/day (50 mg/dose) at 1-week intervals (titration phase). At the beginning of Week 5, patients will enter a 12 week maintenance phase.

Treatment: Drugs: Placebo
Oral tablet.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change in the 28-day Total Partial Seizure (PS) Frequency From Baseline (BL) to the End of the Double-blind (DB) Phase (Titration and Maintenance Phases)
Timepoint [1] 0 0
Baseline (Week -7 through Week 0), DB Phase (Week 1 through Week 16)
Primary outcome [2] 0 0
Number of Participants Classified as Responders and Non-responders During the Maintenance Phase
Timepoint [2] 0 0
Week 5 through Week 16
Secondary outcome [1] 0 0
Number of Participants Who Were Responders and Non-responders During the DB Phase
Timepoint [1] 0 0
Week 1 through Week 16
Secondary outcome [2] 0 0
Percent Change From Baseline (BL) in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Timepoint [2] 0 0
Baseline (Week -7 through Week 0), Week 5 through Week 16
Secondary outcome [3] 0 0
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the End of DB Phase (Titration and Maintenance Phases) by Indicated Quartile Reduction Categories
Timepoint [3] 0 0
Baseline (Week -7 through Week 0), Week 1 through Week 16
Secondary outcome [4] 0 0
Number of Participants With a Reduction in the 28-day Total Partial Seizure Frequency From Baseline to the DB Phase (Titration and Maintenance Phases) by Indicated Decile Reduction and Increase Categories
Timepoint [4] 0 0
Baseline (Week -7 through Week 0), Week 1 through Week 16
Secondary outcome [5] 0 0
Number of Participants With the Indicated Reduction From Baseline in the 28-day Total Partial Seizure Frequency During the Maintenance Phase
Timepoint [5] 0 0
Baseline (Week -7 through Week 0), Week 5 through Week 16
Secondary outcome [6] 0 0
Number of Participants Who Experienced the Indicated Level of Exacerbation and Reduction in the 28-day Total Partial Seizure Frequency From Baseline During the Maintenance Phase
Timepoint [6] 0 0
Baseline (Week -7 through Week 0), Week 5 through Week 16
Secondary outcome [7] 0 0
Number of Participants Reporting New Seizure Types in the Indicated Categories During the DB Phase (Titration and Maintenance Phases) That Were Not Reported at Baseline
Timepoint [7] 0 0
Baseline (Week -7 through Week 0), Week 1 through Week 16
Secondary outcome [8] 0 0
Number of Participants Who Were Seizure-free During the DB Phase (Titration and Maintenance Phases)
Timepoint [8] 0 0
Week 1 through Week 16
Secondary outcome [9] 0 0
Number of Participants Who Were Seizure-free During the Maintenance Phase
Timepoint [9] 0 0
Week 5 through Week 16
Secondary outcome [10] 0 0
Percentage of Seizure-free Days During the DB Phase (Titration and Maintenance Phases)
Timepoint [10] 0 0
Week 1 through Week 16
Secondary outcome [11] 0 0
Percentage of Seizure-free Days During the Maintenance Phase
Timepoint [11] 0 0
Week 5 through Week 16
Secondary outcome [12] 0 0
Clinical Global Impression-Improvement (CGI-I) Score at the End of the Maintenance Phase
Timepoint [12] 0 0
Week 16/end of treatment phase
Secondary outcome [13] 0 0
Patient Global Impression (PGI) Score at the End of the Maintenance Phase
Timepoint [13] 0 0
Week 16/end of treatment phase
Secondary outcome [14] 0 0
Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) at BL (Week 0) and Weeks 4, 8, and 16
Timepoint [14] 0 0
End of Baseline (Week 0), Weeks 4, 8, and 16
Secondary outcome [15] 0 0
Number of Participants Whose Clinical Laboratory Values Were Deemed an Adverse Event by the Investigator (>=2% in Any Treatment Arm)
Timepoint [15] 0 0
Week 1 through Week 16
Secondary outcome [16] 0 0
Number of Participants Who Reported the Indicated Renal and Urinary Disorder Adverse Events at a Frequency Threshold of 2% (in Any Treatment Arm)
Timepoint [16] 0 0
Week 1 through Week 16
Secondary outcome [17] 0 0
Change From Baseline in Post-void Residual Urine Volume at Weeks 8 and 16 of the Maintenance Phase
Timepoint [17] 0 0
Baseline (Week -7 through 0), Weeks 8 and 16
Secondary outcome [18] 0 0
Number of Participants With a >=7% Increase in Body Weight During Weeks 2 and 4 of theTitration Phase and Weeks 6, 8, 12, and 16 of the Maintenance Phase
Timepoint [18] 0 0
Weeks 2 and 4 of Titration Phase and Weeks 6, 8, 12, and 16 of Maintenance Phase

Eligibility
Key inclusion criteria
* Diagnosis of refractory epilepsy with simple or complex partial onset seizures with or without secondary generalization
* 28-day partial seizure frequency rate of four or more partial seizures over the 8-week baseline phase
* Currently treated with up to three established AEDs
* Vagal Nerve Stimulator may be included
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Existing medical or psychiatric condition which could affect patient's health or compromise ability to participate in the study
* Clinically significant abnormalities on physical exam, vital signs, ECG, or liver function tests
* Impaired renal function (creatinine clearance less than 50 mL/minute)
* Evidence of progressive central nervous disease, lesion, or encephalopathy
* History of primary generalized seizures
* History of clustering or flurries or status epilepticus within 12 months of study entry

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2008
Sample size
Target
Accrual to date
Final
539
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
North Coast Neurology Centre - Maroochydore
Recruitment hospital [3] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [5] 0 0
Austin & Repatriation Medical Centre - West Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4558 - Maroochydore
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
3084 - West Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Belgium
State/province [3] 0 0
Antwerp
Country [4] 0 0
Belgium
State/province [4] 0 0
Brugge
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Belgium
State/province [6] 0 0
Ottignies
Country [7] 0 0
France
State/province [7] 0 0
Lyonnais
Country [8] 0 0
France
State/province [8] 0 0
Rennes Cedex
Country [9] 0 0
France
State/province [9] 0 0
Strasbourg
Country [10] 0 0
France
State/province [10] 0 0
Tain L'Hermitage
Country [11] 0 0
Germany
State/province [11] 0 0
Bonn
Country [12] 0 0
Germany
State/province [12] 0 0
Erlangen
Country [13] 0 0
Germany
State/province [13] 0 0
Goettingen
Country [14] 0 0
Germany
State/province [14] 0 0
Mainz
Country [15] 0 0
Germany
State/province [15] 0 0
Marburg
Country [16] 0 0
Germany
State/province [16] 0 0
Munich
Country [17] 0 0
Germany
State/province [17] 0 0
Ulm
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Israel
State/province [19] 0 0
Ashkelon
Country [20] 0 0
Israel
State/province [20] 0 0
Beer Yaakov
Country [21] 0 0
Israel
State/province [21] 0 0
Haifa
Country [22] 0 0
Israel
State/province [22] 0 0
Holon
Country [23] 0 0
Israel
State/province [23] 0 0
Nahariya
Country [24] 0 0
Israel
State/province [24] 0 0
Ramat Gan
Country [25] 0 0
Israel
State/province [25] 0 0
Rechovot
Country [26] 0 0
Israel
State/province [26] 0 0
Tel Aviv
Country [27] 0 0
Poland
State/province [27] 0 0
Plock
Country [28] 0 0
Poland
State/province [28] 0 0
Bialystok
Country [29] 0 0
Poland
State/province [29] 0 0
Gdansk
Country [30] 0 0
Poland
State/province [30] 0 0
Katowice
Country [31] 0 0
Poland
State/province [31] 0 0
Lublin
Country [32] 0 0
Poland
State/province [32] 0 0
Warsaw
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Kazan
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Moscow
Country [35] 0 0
Russian Federation
State/province [35] 0 0
St. Petersburg
Country [36] 0 0
South Africa
State/province [36] 0 0
East Cape
Country [37] 0 0
South Africa
State/province [37] 0 0
Gauteng
Country [38] 0 0
South Africa
State/province [38] 0 0
Gauten
Country [39] 0 0
South Africa
State/province [39] 0 0
KwaZulu-Natal
Country [40] 0 0
South Africa
State/province [40] 0 0
West Cape
Country [41] 0 0
South Africa
State/province [41] 0 0
Western Cape
Country [42] 0 0
South Africa
State/province [42] 0 0
Cape Town
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Bilbao
Country [45] 0 0
Spain
State/province [45] 0 0
Granada
Country [46] 0 0
Spain
State/province [46] 0 0
Madrid
Country [47] 0 0
Spain
State/province [47] 0 0
San Sebastian
Country [48] 0 0
Spain
State/province [48] 0 0
Zaragoza
Country [49] 0 0
Ukraine
State/province [49] 0 0
Dnepropetrovsk
Country [50] 0 0
Ukraine
State/province [50] 0 0
Kharkiv
Country [51] 0 0
Ukraine
State/province [51] 0 0
Kharkov
Country [52] 0 0
Ukraine
State/province [52] 0 0
Kiev
Country [53] 0 0
Ukraine
State/province [53] 0 0
Odessa
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Mersyd
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Blackpool
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Glasgow
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Liverpool
Country [58] 0 0
United Kingdom
State/province [58] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bausch Health Americas, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 3 study is being conducted to evaluate the efficacy and safety of retigabine dosed at 900 mg/day and 600 mg/day, in three equally divided doses, compared with placebo in patients with epilepsy who are receiving up to three established antiepileptic drugs (AEDs).
Trial website
https://clinicaltrials.gov/study/NCT00235755
Trial related presentations / publications
Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010 Nov 16;75(20):1817-24. doi: 10.1212/WNL.0b013e3181fd6170. Epub 2010 Oct 13.
Tompson DJ, Crean CS. Clinical pharmacokinetics of retigabine/ezogabine. Curr Clin Pharmacol. 2013 Nov;8(4):319-31. doi: 10.2174/15748847113089990053.
Brickel N, Gandhi P, VanLandingham K, Hammond J, DeRossett S. The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels. Epilepsia. 2012 Apr;53(4):606-12. doi: 10.1111/j.1528-1167.2012.03441.x. Epub 2012 Mar 16.
Porter RJ, Burdette DE, Gil-Nagel A, Hall ST, White R, Shaikh S, DeRossett SE. Retigabine as adjunctive therapy in adults with partial-onset seizures: integrated analysis of three pivotal controlled trials. Epilepsy Res. 2012 Aug;101(1-2):103-12. doi: 10.1016/j.eplepsyres.2012.03.010. Epub 2012 Apr 16.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00235755