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Open-Label Extension Study of the Phase 3 VRX-RET-E22-302 Double-Blind Trial. 115097

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00310388
First received: March 30, 2006
Last updated: August 14, 2017
Last verified: August 2017
  Purpose
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.

Condition Intervention Phase
Epilepsy Drug: Retigabine (INN), Ezogabine (USAN) Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) for supine and standing position [ Time Frame: Baseline (Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    SBP and DBP measurements for supine and standing position were obtained at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. For the standing position measurement, participant was asked to stand for approximately 2 minutes before taking the measurements. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Month 0 value.

  • Change from baseline in supine and standing pulse rate [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Pulse rate measurements for supine and standing position were obtained at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. For the standing position measurement, participant was asked to stand for approximately 2 minutes before taking the measurements. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Month 0 value.

  • Change from baseline in body weight [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Weight measurements were obtained at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. For measuring weight, participants were asked to be in ordinary indoor clothing (without shoes). The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Month 0 value.

  • Change from baseline in body temperature [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Temperature measurements were obtained at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in Hematology parameters- Basophils, Eosinophils, lymphocytes, Monocytes, Neutrophils, platelet count and white blood corpusles (WBC) [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of hematology parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in Basophils, Eosinophils, lymphocytes, Monocytes, Neutrophils, platelet count and WBC is presented. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in Hematology parameters- Hematocrit [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of hematology parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in hematocrit is presented.The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in Hematology parameters- Hemoglobin [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of hematology parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in hemoglobin is presented. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in Hematology parameters- red blood corpuscles(RBC) [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of hematology parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in RBC is presented. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in clinical chemistry: Alkaline Phosphatase, alanine transaminase (ALT), aspartate transaminase (AST) [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of clinical chemistry parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in Alkaline Phosphatase, ALT and AST is presented. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in clinical chemistry : bicarbonate, BUN, calcium, chloride, cholesterol, non-fasting glucose, phosphorus, potassium, sodium [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of clinical chemistry parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in bicarbonate, BUN, calcium, chloride, cholesterol, non-fasting glucose, phosphorus, potassium, sodium is presented. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in clinical chemistry: Total Bilirubin, Creatinine, Uric acid [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of clinical chemistry parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in total bilirubin, creatinine and uric acid is presented. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change from baseline in clinical chemistry: Total protein [ Time Frame: Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24 ]
    Blood samples were collected for the measurement of clinical chemistry parameters at Baseline(Month 0) and Month 1, 3, 6, 9, 12, 16, 20, 24. Change from baseline in total protein is presented. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • ECG parameters assessment: PR interval, QRS interval, QT interval, and QTc interval [ Time Frame: Month 1, 3, 6, 9, 12 and 24 ]
    A 12-lead ECG was performed at Month 1, 3, 6, 9, 12 and 24. The ECG parameters assessed were PR interval, QRS interval, QT interval, and QTc interval. QT intervals were corrected using both Bazett's and Fridericia's formulas. Increases in Bazett's QTc interval of >60 from baseline or QTc interval of >500 anytime during the was confirmed on a repeat ECG.

  • Number of participants with abnormal Physical and neurological examinations [ Time Frame: Up to Month 24 ]
    Physical examination included skin, head, eyes, ears, nose, throat, mouth, neck, heart, lungs, breast, abdomen, genitalia, extremities and other. Neurological examination included level of consciousness, level of appearance, mental status, speech, vision, eye movements, jaw movements and facial sensation, facial motor, hearing, swallowing, pharynx, larynx, sternocleidomastoid, trapezius, tongue, biceps, brachioradials, triceps, knee, ankle, plantar, general movement, muscle bulk, muscle fasciculation, trunk, muscle strength upper extremities, muscle strength lower extremities, muscle tone upper extremities, muscle tone lower extremities, gait, hopping, romberg, nystagmus, tremor, finger-nose, heel-shin, rapid rhythmic movements, upper extremities pain/ temperature, upper extremities light touch, upper extremities position, upper extremities vibration, lower extremities pain/ temperature, lower extremities light touch, lower extremities position and lower extremities vibration.

  • Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 24 months ]
    An AE is defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

  • Change From Baseline in American Urological Association (AUA) Symptom Index Scores During Open-Label Retigabine Treatment [ Time Frame: Baseline (month 0) and Month 1, 3 and 12 ]
    AUA symptom index scores questionnaire had 7 questions. Responses to each of the 7 questions were scored 0 (not at all), 1 (less than 1 time), 2 (less than half the time), 3 (about half the time), 4 (more than half the time) and 5 (almost always), for a total possible score of 35. The total score for all questions was classified as mild (0-7), moderate (8-19) or severe (>19). Question 7 was scored as 0 (none), 1 (1 time), 2 (2 times), 3 (3 times), 4 (4 times) and 5 (5 times or more). Total score was range was 0-49.The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Change From Baseline in Post-Void Residual Urine Volume by Study Time Point [ Time Frame: Baseline (month 0) and Month 1, 3 and 12 ]
    A post-void residual bladder ultrasound to assess urinary retention was performed at Baseline (month 0) and Month 1, 3 and 12. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.


Secondary Outcome Measures:
  • Change from baseline in Quality of life, evaluated through the Quality of Life in Epilepsy-Problems (QOLIE-31-P) [ Time Frame: Baseline (Month 0) and Month 24 ]
    The Quality of Life in Epilepsy Inventory-Form 31 (QOLIE-31-P) is an adaptation of the original QOLIE-31 instrument that includes 30 items grouped into 7 multi-item subscales: Seizure Worry (5 items), Overall Quality of Life (2 items), Emotional Well-being (5 items), Energy/Fatigue (4 items), Cognitive Functioning (6 items), Medication Effects (3 items) and Daily Activities/Social Functioning (5 items), and a Health Status item. In addition to the 31 items, the QOLIE-31-P contains 7 items asking the participants to rate the degree of 'distress' related to the topic of each subscale. The subscale scores, the total score and the Health Status item score were calculated according to the scoring algorithm defined by the author with scores ranging from 0 to 100 and higher scores indicating better function. The change from Baseline was obtained by subtracting the Baseline value from the post randomization value. Baseline was Month 0 value.

  • Percentage change in the monthly seizure rate from the baseline (Study 302) phase to the open-label treatment phase [ Time Frame: Baseline (Month 0) and Month 24 ]
    Monthly total seizure rates observed during the open-label extension period was compared to the monthly total seizure rates observed during the Baseline phase of the double-blind study VRX-RET-E22-302. Percent change from baseline was calculated as post randomization value divided by the baseline value and multiplied by 100. Baseline was Month 0 value of VRX-RET-E22-302 study.

  • Number of participants who were responders (participants experiencing ≥ 50% reduction in seizure frequency) from baseline to open-label treatment phase [ Time Frame: At Month 24 ]
    Responders were defined as participants with ≥50% reduction in 28-day total partial seizure frequency from Baseline in Study 302 to data cutoff in this Study 304. Number of participants who were responders are presented.


Enrollment: 376
Actual Study Start Date: July 5, 2006
Estimated Study Completion Date: April 19, 2018
Primary Completion Date: April 19, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Retigabine (INN), Ezogabine (USAN)
Retigabine (Ezogabine): all subjects
Drug: 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.
Other Names:
  • GW582892X
  • D-23129
  • GKE-841

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

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310388

  Hide Study Locations
Locations
Australia, New South Wales
Institute of Clniical Neurosciences
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
North Coast Neurology Centre
Maroochydore, Queensland, Australia, 4558
Australia, South Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia, 5041
Australia, Victoria
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Austin & Repatriation Medical Centre
West Heidelberg, Victoria, Australia, 3081
Belgium
General Hospital Middelheim -- Department of Neurology
Antwerp, Belgium, B-2020
AZ Sint-Jan
Brugge, Belgium, 8000
Universitaire Ziekenhuizen Gasthuisberg -- Department Neurology
Leuven, Belgium, 3000
Centre Neurologique William Lennox
Ottignies, Belgium, 1340
France
Hopital Civil de Steasbourg Clinique Neurologie
Levallois-Perret, France, 92594
Hopital Neurologique Pierre Wertheimer
Lyon, France, 69003
CHU Pontchaillou
Rennes Cedex, France, 35033
Centre Medical de La Teppe
Tain L'Hermitage, 26, France, 26600
Germany
Zentrum Epilepsie Erlangen (ZEE) der Universitaet Erlangen
Erlangen, BY, Germany, 91054
Universitaet Giessen / Marburg Neurologie
Marburg, HE, Germany, 35033
Universitaetsklinik Mainz Neurologische Klinik
Mainz, RP, Germany, 55101
University of Bonn -- Department for Epileptplogy
Bonn, Germany, D-53105
Private Neurologische Paraxis
Muenchen, BY, Germany, 80333
Universitaetslinkum Ulm Poliklinik fuer Neurologie
Ulm, BW, Germany, 89081
Hungary
Pecs University of Science, Clinic of Neurology
Pecs, Ret, Hungary, U2
Orszagos Pszichiatriai es Neurologiai Intezet
Budapest, Hungary, 1021
Orszagos Idegsebeszeti Tudomanyos Intezet
Budapest, Hungary, 1145
Israel
Assaf Harofeh Medical Center
Beer Yaakov, Israel, 70300
Rambam Medical Center
Haifa, Israel, 31096
Wolfson Medical Center
Holon, Israel, 58100
Western Galilee Hospital
Nahariya, Israel, 22100
Chaim Sheba Medical Center
Ramat Gan, Israel, 52621
Kaplan Medical Center
Rechovot, Israel, 76100
Tel-Aviv Sourasky Medical Center
Tel Aviv, Israel, 64239
Poland
Specjalistyczna Przychodnia Lekarska Medikard
Padlewskiego 4, Plock, Poland, 09-402
Prywatna Wielospecjalistyczna Lecznica Medyczna "Zycie"
Plac Hallera 5, Warszawa, Poland, 03-464
Oddzial Neurologii -- Klinika Neurologii ICZMP
U1. Parzeczewska 35, Zgierz, Poland, 95-100
NZOZ Przychodnia Internistyczno - Stomatologiczna "Kendron"
Bialystok, Poland
Wojewodzki Szpital Specjalistyczny im.Mikolaja Kopernika
Gdansk, Poland, 80-803
WSS im.Kardynala S. Wyszynskiego
Lublin, Poland, 20-718
Instytut Psychiatrii i Neurologii II Oddzial Neurologii
Warszawa, Poland, 02-957
Russian Federation
Kazan State Medical University
Kazan, Russian Federation, 420012
City Hospital # 1
Moscow, Russian Federation, 117049
City Hospital # 33
Moscow, Russian Federation
District Antiepileptic Centre City Clinical Hospital # 71
Moscow, Russian Federation
Russian Military Medical Academy
St. Petersburg, Russian Federation, 194044
Pavlov State Medical University Clinic and Department of Neurology
St. Petersburg, Russian Federation
South Africa
Sunninghill & Kopano Clinical Trials
Johannesburg, Gauteng, South Africa, 2157
Wilgers MR & Medical Centre
Pretoria, Gauteng, South Africa, 0001
Panorama Medi-Clinic
Parow, W Cape, South Africa, 7550
Groote Schuur Hospital
Cape Town, WC, South Africa, 7925
Carl Bremer Hospital
Belville, W Cape, South Africa, 7531
Farmovs Parexel
BleomFontein, Free State, South Africa, 9300
Inkosi Albert Luthuli Central Hospital
Durban, KZ-Natal, South Africa, 4091
Johannesburg Hospital
Johannesburg, Gauteng, South Africa, 2193
Triple M Research
Port Elisabeth, E Cape, South Africa, 6001
Spain
Hospital Sta. Creu i S. Pau
Barcelona, Spain, 08025
Hospital de Cruces Neurology Department
Bilbao, Spain, 48903
Hosp. Virgen de las Nieves
Granada, Spain, 18014
Hospital Ruber Internacional de Madrid
Madrid, Spain, 28034
Fundacion Jimenez Diaz
Madrid, Spain, 28040
Hosp. de Donostia Neurology Department
San Sebastian, Spain, 20014
Hospital Universitario Lozano Blesa Neurology Service
Zaragoza, Spain, 50009
Ukraine
Psychosomatic Center of Dnepropetr. Regional Clinic
Dnepropetrovsk, Ukraine, 49616
Kharkov State Medical University
Kharkov, Ukraine, 31002
Institute of Neurology, Psychiatry and Narcology of AMS, Ukr
Kharkov, Ukraine, 31068
Epilepsy Center of Municipal Clinical Psychoneurological Hospital
Kiev, Ukraine, 04080
Odessa Regional Clinical Hospital Center for Neurology and Neurosurgery
Odessa, Ukraine, 65025
United Kingdom
The James Cook University Hospital
Middlesbrough, Mersyd, United Kingdom, TS4 3BY
Fylde Coast Hospital
Blackpool, United Kingdom, FY3 8BP
Western Infirmary (Epilepsy)
Glasgow, United Kingdom, G11 6NT
Royal London Hospital
London, United Kingdom, GT LON E1 1BB
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00310388     History of Changes
Other Study ID Numbers: VRX-RET-E22-304
EUDRACT No. 2006-000956-42
RTG115097 ( Other Identifier: GlaxoSmithKline )
Study First Received: March 30, 2006
Last Updated: August 14, 2017

Keywords provided by GlaxoSmithKline:
Partial Seizures
Epilepsy
RTG115097
Complex Partial Seizures
Anticonvulsant
Potassium Channels
Epilepsies, Partial

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Ezogabine
Anticonvulsants
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 21, 2017