Clinical trial NCT00310388: Open-Label Extension Study of the Phase 3 VRX-RET-E22-302 Double-Blind Trial. 115097
Official 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Partial Seizures
Epilepsy
RTG115097
Complex Partial Seizures
Anticonvulsant
Potassium Channels
Epilepsies, Partial
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-04-03
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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 retigabine is commercially available, or until the program is discontinued. Patients will be recruited from 55-60 sites in Europe, Israel, Australia, and South Africa. The safety and tolerability of long-term therapy with retigabine administered as adjunctive therapy in adult epilepsy patients with partial-onset seizures will be evaluated. In addition, the efficacy of long-term treatment with retigabine and patient quality of life will be assessed.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)
timeFrame: Up to 122 months
measure: Number of Participants With TEAEs Leading to Treatment Discontinuation (Disc.)
timeFrame: Up to 122 months
measure: Kaplan-Meier Estimate of the Probability of Disc. From Study Drug
timeFrame: Up to 122 months
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Measurements in the Supine and Standing Position
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Heart Rate (HR) Measurements in the Supine and Standing Position
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Body Temperature
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Body Weight
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Electocardiogram (ECG) Parameters PR, QRS, QT, Corrected QT Interval (QTc) Bazett and QTc Friedericia
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Alkaline Phosphatase (Alk. Phos.), Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST)
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Non-fasting Glucose, Phosphorus, Potassium, Sodium and Urea
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Creatinine, Total Bilirubin and Uric Acid
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Total Protein
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count, White Blood Cells (WBC)
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Hematocrit
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Hemoglobin
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Hematology Parameter Red Blood Cells (RBC)
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Urine Specific Gravity
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Urine Potential of Hydrogen (pH)
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Post-Void Residual (PVR) Bladder Ultrasound Volume
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in the Urinary Voiding Function [UVF] (Assessed Using the American Urological Association [AUA] Symptom Index)
timeFrame: Baseline and up to 122 months
measure: Change From Baseline in Quality of Life in Epilepsy-31-Problems (QOLIE-31-P) Questionnaire
timeFrame: Baseline and up to 122 months
measure: Percentage of Participants With Abnormal Results of Physical Examination
timeFrame: Baseline and up to 122 months
measure: Percentage of Participants With Abnormal Results of Neurological Examination
timeFrame: Baseline and up to 122 months
Secondary outcomes:
measure: Percentage of Participants With Retinal Pigmentary Abnormalities (RPA)
timeFrame: Up to 121 months
measure: Percentage of Participants With Pigmentation of Non-retinal Ocular Tissue (Non-ret. Pig. Abn)
timeFrame: Up to 121 months
measure: Percentage of Participants With Abnormal Pigmentation of Skin, Including the Skin Around the Eyes and the Eyelids, Lips, Nails, or Mucosa
timeFrame: Up to 121 months
measure: Percentage of Participants With a Clinically Significant Decrease (CSD) in Visual Acuity (VA) From Initial Examination
timeFrame: Up to 121 months
measure: Percentage of Participants With Decrease in Confrontation Visual Field From Initial Examination
timeFrame: Up to 121 months
measure: Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine
timeFrame: 3 years and 10 months
measure: Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine
timeFrame: 3 years and 10 months
measure: Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation
timeFrame: 3 years and 10 months
measure: Time From Discontinuation of Retigabine to Resolution of All Dermatologist-Confirmed Abnormal Discoloration
timeFrame: 3 years and 10 months
measure: 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.
timeFrame: Baseline and up to 121 months
measure: Percentage of Participants With 50% Reduction in Seizure Frequency From Baseline Phase of the Parent Study (VRX-RET-E22-302) to Open Label Treatment
timeFrame: Baseline and up to 121 months
measure: Number of Participants Who Were Seizure Free for Any 6 Continuous Months
timeFrame: Up to 6 continuous months within the 121 months period
measure: Number of Participants Who Were Seizure Free for Any 12 Continuous Months
timeFrame: Up to 12 continuous months within the 121 months period
measure: Percentage of Seizure Free Days
timeFrame: Up to 121 months
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Institute of Clniical Neurosciences
state: New South Wales
city: Maroochydore
country: Australia
facility: North Coast Neurology Centre
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: West Heidelberg
country: Australia
facility: Austin & Repatriation Medical Centre
state: Victoria
city: Antwerp
country: Belgium
facility: General Hospital Middelheim -- Department of Neurology
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology
city: Ottignies
country: Belgium
facility: Centre Neurologique William Lennox
city: Levallois-Perret
country: France
facility: Hopital Civil de Steasbourg Clinique Neurologie
city: Lyon
country: France
facility: Hopital Neurologique Pierre Wertheimer
city: Rennes Cedex
country: France
facility: CHU Pontchaillou
city: Tain L'Hermitage, 26
country: France
facility: Centre Medical de La Teppe
city: Erlangen
country: Germany
facility: Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen
state: BY
city: Marburg
country: Germany
facility: Universitaet Giessen / Marburg Neurologie
state: HE
city: Mainz
country: Germany
facility: Universitaetsklinik Mainz Neurologische Klinik
state: RP
city: Bonn
country: Germany
facility: University of Bonn -- Department for Epileptplogy
city: Muenchen, BY
country: Germany
facility: Private Neurologische Paraxis
city: Ulm, BW
country: Germany
facility: Universitaetslinkum Ulm Poliklinik fuer Neurologie
city: Pecs
country: Hungary
facility: Pecs University of Science, Clinic of Neurology
state: Ret
city: Budapest
country: Hungary
facility: Orszagos Pszichiatriai es Neurologiai Intezet
city: Budapest
country: Hungary
facility: Orszagos Idegsebeszeti Tudomanyos Intezet
city: Beer Yaakov
country: Israel
facility: Assaf Harofeh Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Nahariya
country: Israel
facility: Western Galilee Hospital
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rechovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Padlewskiego 4
country: Poland
facility: Specjalistyczna Przychodnia Lekarska Medikard
state: Plock
city: Plac Hallera 5
country: Poland
facility: Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"
state: Warszawa
city: U1. Parzeczewska 35
country: Poland
facility: Oddzial Neurologii -- Klinika Neurologii ICZMP
state: Zgierz
city: Bialystok
country: Poland
facility: NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"
city: Gdansk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika
city: Lublin
country: Poland
facility: WSS im.Kardynala S. Wyszynskiego
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii II Oddzial Neurologii
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Moscow
country: Russian Federation
facility: City Hospital # 1
city: Moscow
country: Russian Federation
facility: City Hospital # 33
city: Moscow
country: Russian Federation
facility: District Antiepileptic Centre City Clinical Hospital # 71
city: St. Petersburg
country: Russian Federation
facility: Russian Military Medical Academy
city: St. Petersburg
country: Russian Federation
facility: Pavlov State Medical University Clinic and Department of Neurology
city: Johannesburg
country: South Africa
facility: Sunninghill & Kopano Clinical Trials
state: Gauteng
city: Pretoria
country: South Africa
facility: Wilgers MR & Medical Centre
state: Gauteng
city: Parow
country: South Africa
facility: Panorama Medi-Clinic
state: W Cape
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
state: WC
city: Belville, W Cape
country: South Africa
facility: Carl Bremer Hospital
city: BleomFontein, Free State
country: South Africa
facility: Farmovs Parexel
city: Durban, KZ-Natal
country: South Africa
facility: Inkosi Albert Luthuli Central Hospital
city: Johannesburg, Gauteng
country: South Africa
facility: Johannesburg Hospital
city: Port Elisabeth, E Cape
country: South Africa
facility: Triple M Research
city: Barcelona
country: Spain
facility: Hospital Sta. Creu i S. Pau
city: Bilbao
country: Spain
facility: Hospital de Cruces Neurology Department
city: Granada
country: Spain
facility: Hosp. Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Ruber Internacional de Madrid
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: San Sebastian
country: Spain
facility: Hosp. de Donostia Neurology Department
city: Zaragoza
country: Spain
facility: Hospital Universitario Lozano Blesa Neurology Service
city: Dnepropetrovsk
country: Ukraine
facility: Psychosomatic Center of Dnepropetr. Regional Clinic
city: Kharkov
country: Ukraine
facility: Kharkov State Medical University
city: Kharkov
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of AMS, Ukr
city: Kiev
country: Ukraine
facility: Epilepsy Center of Municipal Clinical Psychoneurological Hospital
city: Odessa
country: Ukraine
facility: Odessa Regional Clinical Hospital Center for Neurology and Neurosurgery
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
state: Mersyd
city: Blackpool
country: United Kingdom
facility: Fylde Coast Hospital
city: Glasgow
country: United Kingdom
facility: Western Infirmary (Epilepsy)
city: London
country: United Kingdom
facility: Royal London Hospital
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: