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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00310388




Registration number
NCT00310388
Ethics application status
Date submitted
30/03/2006
Date registered
3/04/2006
Date last updated
15/11/2018

Titles & IDs
Public title
Open-Label Extension Study of the Phase 3 VRX-RET-E22-302 Double-Blind Trial. 115097
Scientific title
A Multicenter, Open-Label, Long-Term, Safety, Tolerability and Efficacy Study of Retigabine in Adult Epilepsy Patients With Partial-Onset Seizures (Extension of Study VRX-RET-E22-302)
Secondary ID [1] 0 0
EUDRACT No. 2006-000956-42
Secondary ID [2] 0 0
VRX-RET-E22-304
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Retigabine (INN), Ezogabine (USAN)

Experimental: Retigabine (INN), Ezogabine (USAN) - Retigabine (Ezogabine): all subjects


Treatment: Drugs: Retigabine (INN), Ezogabine (USAN)
Film-coated tablets containing 50 mg, 100 mg, or 300 mg of retigabine per tablet. Dosage and frequency will be specific to each patient so long as the patients receives between 600 and 1200 mg of retigabine per day. The duration will be until the completion of the trial, or until the patient withdraws from the trial.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)
Timepoint [1] 0 0
Up to 122 months
Primary outcome [2] 0 0
Number of Participants With TEAEs Leading to Treatment Discontinuation (Disc.)
Timepoint [2] 0 0
Up to 122 months
Primary outcome [3] 0 0
Kaplan-Meier Estimate of the Probability of Disc. From Study Drug
Timepoint [3] 0 0
Up to 122 months
Primary outcome [4] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Measurements in the Supine and Standing Position
Timepoint [4] 0 0
Baseline and up to 122 months
Primary outcome [5] 0 0
Change From Baseline in Heart Rate (HR) Measurements in the Supine and Standing Position
Timepoint [5] 0 0
Baseline and up to 122 months
Primary outcome [6] 0 0
Change From Baseline in Body Temperature
Timepoint [6] 0 0
Baseline and up to 122 months
Primary outcome [7] 0 0
Change From Baseline in Body Weight
Timepoint [7] 0 0
Baseline and up to 122 months
Primary outcome [8] 0 0
Change From Baseline in Electocardiogram (ECG) Parameters PR, QRS, QT, Corrected QT Interval (QTc) Bazett and QTc Friedericia
Timepoint [8] 0 0
Baseline and up to 122 months
Primary outcome [9] 0 0
Change From Baseline in Alkaline Phosphatase (Alk. Phos.), Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST)
Timepoint [9] 0 0
Baseline and up to 122 months
Primary outcome [10] 0 0
Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium and Urea
Timepoint [10] 0 0
Baseline and up to 122 months
Primary outcome [11] 0 0
Change From Baseline in Creatinine, Total Bilirubin and Uric Acid
Timepoint [11] 0 0
Baseline and up to 122 months
Primary outcome [12] 0 0
Change From Baseline in Total Protein
Timepoint [12] 0 0
Baseline and up to 122 months
Primary outcome [13] 0 0
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, White Blood Cells (WBC)
Timepoint [13] 0 0
Baseline and up to 122 months
Primary outcome [14] 0 0
Change From Baseline in Hematocrit
Timepoint [14] 0 0
Baseline and up to 122 months
Primary outcome [15] 0 0
Change From Baseline in Hemoglobin
Timepoint [15] 0 0
Baseline and up to 122 months
Primary outcome [16] 0 0
Change From Baseline in Hematology Parameter Red Blood Cells (RBC)
Timepoint [16] 0 0
Baseline and up to 122 months
Primary outcome [17] 0 0
Change From Baseline in Urine Specific Gravity
Timepoint [17] 0 0
Baseline and up to 122 months
Primary outcome [18] 0 0
Change From Baseline in Urine Potential of Hydrogen (pH)
Timepoint [18] 0 0
Baseline and up to 122 months
Primary outcome [19] 0 0
Change From Baseline in Post-Void Residual (PVR) Bladder Ultrasound Volume
Timepoint [19] 0 0
Baseline and up to 122 months
Primary outcome [20] 0 0
Change From Baseline in the Urinary Voiding Function [UVF] (Assessed Using the American Urological Association [AUA] Symptom Index)
Timepoint [20] 0 0
Baseline and up to 122 months
Primary outcome [21] 0 0
Change From Baseline in Quality of Life in Epilepsy-31-Problems (QOLIE-31-P) Questionnaire
Timepoint [21] 0 0
Baseline and up to 122 months
Primary outcome [22] 0 0
Percentage of Participants With Abnormal Results of Physical Examination
Timepoint [22] 0 0
Baseline and up to 122 months
Primary outcome [23] 0 0
Percentage of Participants With Abnormal Results of Neurological Examination
Timepoint [23] 0 0
Baseline and up to 122 months
Secondary outcome [1] 0 0
Percentage of Participants With Retinal Pigmentary Abnormalities (RPA)
Timepoint [1] 0 0
Up to 121 months
Secondary outcome [2] 0 0
Percentage of Participants With Pigmentation of Non-retinal Ocular Tissue (Non-ret. Pig. Abn)
Timepoint [2] 0 0
Up to 121 months
Secondary outcome [3] 0 0
Percentage of Participants With Abnormal Pigmentation of Skin, Including the Skin Around the Eyes and the Eyelids, Lips, Nails, or Mucosa
Timepoint [3] 0 0
Up to 121 months
Secondary outcome [4] 0 0
Percentage of Participants With a Clinically Significant Decrease (CSD) in Visual Acuity (VA) From Initial Examination
Timepoint [4] 0 0
Up to 121 months
Secondary outcome [5] 0 0
Percentage of Participants With Decrease in Confrontation Visual Field From Initial Examination
Timepoint [5] 0 0
Up to 121 months
Secondary outcome [6] 0 0
Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine
Timepoint [6] 0 0
3 years and 10 months
Secondary outcome [7] 0 0
Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine
Timepoint [7] 0 0
3 years and 10 months
Secondary outcome [8] 0 0
Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation
Timepoint [8] 0 0
3 years and 10 months
Secondary outcome [9] 0 0
Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration
Timepoint [9] 0 0
3 years and 10 months
Secondary outcome [10] 0 0
Percentage Change in the 28-day Partial Seizure Rate From the Baseline Phase (Obtained During the 8-week Baseline Period of Study VRX-RET-E22-302) to Open-label Treatment.
Timepoint [10] 0 0
Baseline and up to 121 months
Secondary outcome [11] 0 0
Percentage of Participants With 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment
Timepoint [11] 0 0
Baseline and up to 121 months
Secondary outcome [12] 0 0
Number of Participants Who Were Seizure Free for Any 6 Continuous Months
Timepoint [12] 0 0
Up to 6 continuous months within the 121 months period
Secondary outcome [13] 0 0
Number of Participants Who Were Seizure Free for Any 12 Continuous Months
Timepoint [13] 0 0
Up to 12 continuous months within the 121 months period
Secondary outcome [14] 0 0
Percentage of Seizure Free Days
Timepoint [14] 0 0
Up to 121 months

Eligibility
Key inclusion criteria
* Patient has successfully completed the Maintenance and Transition phases of Study VRX-RET-E22-302 for the treatment of partial-onset seizures
* Patient is expected to benefit from participation in the study in the opinion of the Investigator.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patient meets any of the withdrawal criteria in the previous VRX-RET-E22-302 study or is experiencing an ongoing serious adverse event.
* Patient is receiving any investigational drug or using any experimental device in addition to Retigabine for treatment of epilepsy or any other medical condition.
* Patient has any other condition that would prevent compliance with the study procedures or proper reporting of adverse events.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/07/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/05/2018
Sample size
Target
Accrual to date
Final
376
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Institute of Clniical Neurosciences - Camperdown
Recruitment hospital [2] 0 0
North Coast Neurology Centre - Maroochydore
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
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
5041 - Bedford Park
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment postcode(s) [5] 0 0
3081 - West Heidelberg
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerp
Country [2] 0 0
Belgium
State/province [2] 0 0
Brugge
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Ottignies
Country [5] 0 0
France
State/province [5] 0 0
Levallois-Perret
Country [6] 0 0
France
State/province [6] 0 0
Lyon
Country [7] 0 0
France
State/province [7] 0 0
Rennes Cedex
Country [8] 0 0
France
State/province [8] 0 0
Tain L'Hermitage, 26
Country [9] 0 0
Germany
State/province [9] 0 0
BY
Country [10] 0 0
Germany
State/province [10] 0 0
HE
Country [11] 0 0
Germany
State/province [11] 0 0
RP
Country [12] 0 0
Germany
State/province [12] 0 0
Bonn
Country [13] 0 0
Germany
State/province [13] 0 0
Muenchen, BY
Country [14] 0 0
Germany
State/province [14] 0 0
Ulm, BW
Country [15] 0 0
Hungary
State/province [15] 0 0
Ret
Country [16] 0 0
Hungary
State/province [16] 0 0
Budapest
Country [17] 0 0
Israel
State/province [17] 0 0
Beer Yaakov
Country [18] 0 0
Israel
State/province [18] 0 0
Haifa
Country [19] 0 0
Israel
State/province [19] 0 0
Holon
Country [20] 0 0
Israel
State/province [20] 0 0
Nahariya
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Israel
State/province [22] 0 0
Rechovot
Country [23] 0 0
Israel
State/province [23] 0 0
Tel Aviv
Country [24] 0 0
Poland
State/province [24] 0 0
Plock
Country [25] 0 0
Poland
State/province [25] 0 0
Warszawa
Country [26] 0 0
Poland
State/province [26] 0 0
Zgierz
Country [27] 0 0
Poland
State/province [27] 0 0
Bialystok
Country [28] 0 0
Poland
State/province [28] 0 0
Gdansk
Country [29] 0 0
Poland
State/province [29] 0 0
Lublin
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Kazan
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Moscow
Country [32] 0 0
Russian Federation
State/province [32] 0 0
St. Petersburg
Country [33] 0 0
South Africa
State/province [33] 0 0
Gauteng
Country [34] 0 0
South Africa
State/province [34] 0 0
W Cape
Country [35] 0 0
South Africa
State/province [35] 0 0
WC
Country [36] 0 0
South Africa
State/province [36] 0 0
Belville, W Cape
Country [37] 0 0
South Africa
State/province [37] 0 0
BleomFontein, Free State
Country [38] 0 0
South Africa
State/province [38] 0 0
Durban, KZ-Natal
Country [39] 0 0
South Africa
State/province [39] 0 0
Johannesburg, Gauteng
Country [40] 0 0
South Africa
State/province [40] 0 0
Port Elisabeth, E Cape
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Bilbao
Country [43] 0 0
Spain
State/province [43] 0 0
Granada
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
San Sebastian
Country [46] 0 0
Spain
State/province [46] 0 0
Zaragoza
Country [47] 0 0
Ukraine
State/province [47] 0 0
Dnepropetrovsk
Country [48] 0 0
Ukraine
State/province [48] 0 0
Kharkov
Country [49] 0 0
Ukraine
State/province [49] 0 0
Kiev
Country [50] 0 0
Ukraine
State/province [50] 0 0
Odessa
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Mersyd
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Blackpool
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Glasgow
Country [54] 0 0
United Kingdom
State/province [54] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 3 trial is an open-label extension study of the placebo-controlled, double-blind VRX-RET-E22-302 trial. Patients who have completed the VRX-RET-E22-302 trial and who meet inclusion and exclusion criteria will be treated with 600-1200 mg/day of retigabine as an adjunct therapy to their current antiepileptic drugs (AEDs) or vagal nerve stimulation. Treatment will be continued until the subject withdraws from the study or until the program is discontinued. Patients will be recruited from 55-60 sites in Europe, Israel, Australia, and South Africa. The primary objective of the study is to evaluate the safety and tolerability of long-term therapy with retigabine administered as adjunctive therapy in adult epilepsy patients with partial-onset seizures, who completed the double-blind Study VRX-RET-E22-302. Secondary objectives are: to evaluate efficacy of long-term treatment with retigabine and patient quality of life and to evaluate whether retinal pigmentation, unexplained vision loss, pigmentation of non-retinal ocular tissue, and discoloration of nails, lips, skin or mucosa change over time after discontinuation of retigabine.
Trial website
https://clinicaltrials.gov/study/NCT00310388
Trial related presentations / publications
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/NCT00310388