An Open Label Study to Evaluate the Effects of Ezogabine/Retigabine Added to Existing Anti-epileptic Drug(s) on Urinary Voiding Function in Subjects With Partial Onset Seizures

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01607346
First received: May 17, 2012
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

This is an open-label, 10-week study to further investigate the effect of ezogabine/retigabine IR added to the existing antiepileptic drug(s), on the voiding function of epilepsy subjects with partial onset seizures (POS). This will be achieved with repeat urodynamic measurements while the subjects are receiving increasing doses of ezogabine/retigabine IR. The urine voiding function and symptoms will be evaluated through an uroflowmetry measuring unit, post void residual bladder ultrasound and administration of the American Urological Association Symptom Index (AUA SI) for the assessment of lower urinary tract symptoms. Along with at home urine volume measuring and voiding diaries. In addition, subjects who meet pre-determined criteria for voiding dysfunction will undergo multichannel cystometry in order to characterise bladder hypocontractility, bladder outlet obstruction or a combination of events which clinically is manifest with difficulty emptying the bladder or acute urinary retention.

Subjects who meet cystometry criteria during the study must enter the Taper Phase of the study to taper off ezogabine/retigabine. Subjects who do not meet cystometry criteria and if appropriate along with agreement of the Principal Investigator, may choose not to enter the Taper Phase and transition to commercially available ezogabine/retigabine.


Condition Intervention Phase
Epilepsy
Drug: ezogabine/retigabine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study to Evaluate the Effects of Ezogabine/Retigabine Added to Existing Anti-epileptic Drug(s) on Urinary Voiding Function in Subjects With Partial Onset Seizures

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Uroflowmetry: change from baseline in Maximum Flow Rate (Qmax) at Visit 5. [ Time Frame: Day 49 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Uroflowmetry: change from baseline in Maximum Flow Rate (Qmax) at Visits 3, 4 and 6. [ Time Frame: Day 21, 35 and 70 ] [ Designated as safety issue: Yes ]
  • PVR Bladder Ultrasound: change from baseline in % Residual Urinary Volume (RUV) at Visits 3, 4, 5 and 6. [ Time Frame: Day 21, 35, 49 and 70 ] [ Designated as safety issue: Yes ]
  • Uroflowmetry: change from baseline in Voided Volume (VV), Time to Maximum Flow, Flow Time baseline, and Average Flow Rate (Qmean) at each post-baseline visit. [ Time Frame: Day 21-70 ] [ Designated as safety issue: Yes ]
  • Voiding Diary: frequency of micturition and volume voided as recorded on the Voiding Diary for 2 days prior to each post-baseline visit. [ Time Frame: Day 21-70 ] [ Designated as safety issue: Yes ]
  • AUA Symptom Index: change from baseline in the America Urological Association Symptom Index (AUA SI) at each post-baseline visit. [ Time Frame: Day 21-70 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: March 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ezogabine/retigabine
Open-label
Drug: ezogabine/retigabine
Starting dose of 300mg/day, titrate up to a targeted maximum dose of 1200 mg/day. Dose can be reduced to a minimum of 600 mg/day if unable to tolerate higher doses

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is ≥18 years of age (male or female)
  • Has a confident diagnosis of epilepsy with partial onset seizures with or without secondary generalization (classified according to International League Against Epilepsy (ILAE) Guidelines, 1981) ≥ 2 years
  • Is currently being treated with a stable regimen of one to three AEDs during the 4 weeks prior to the Screening Visit. Note: Vagus Nerve Stimulator (VNS)VNS will not be counted as a concurrent AED. Subjects with surgically implanted VNS will be allowed to enter the study provided that all of the following conditions are met: The VNS has been in place for at least 24 weeks prior to the Screening Visit. The settings must remain the same for at least 4 weeks prior to the Screening Visit and throughout the study. The battery is expected to last for the duration of the study. Subject who are considering implantation of a VNS are excluded from participating in this study. Note: The chronic use of benzodiazepines as a concurrent AED is permitted as long as the dose is kept constant for at least 4 weeks before the Screen Visit and throughout the study.
  • Is able and willing to maintain an accurate and complete a two (2) day Voiding Diary at protocol specified time points.
  • Is able and willing to maintain an accurate and complete daily written Seizure Calendar at specified time points or has a caregiver who is able and willing to maintain an accurate and complete daily written Seizure Calendar for the entire duration of the study
  • Has given written informed consent, prior to the performance of any study assessments.
  • A female subject is eligible to enter and participate in the study if she is not pregnant or lactating or planning to become pregnant during the study and is of: Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal). Pre-menopausal females with a documented (medical report verification) hysterectomy with or without oophorectomy or bi-lateral oophorectomy when reproductive status has been confirmed by hormone level assessment Post-menopausal females defined as being amenorrhoeic for greater than one year with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms). However, if indicated, this should be confirmed by oestradiol and follicle stimulating hormone (FSH) levels consistent with menopause (according to local laboratory ranges). Women who have not been confirmed as post-menopausal should be advised to use contraception as outlined in Child-bearing potential, has a negative pregnancy test at screening and baseline, and agrees to satisfy one of the requirements in as listed in Appendix 2.
  • Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2 x upper limit of normal (ULN); alkaline phosphatase and bilirubin less than or equal to 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Has a normal creatinine clearance (age corrected) as calculated with the Cockcroft- Gault formula.

Exclusion Criteria:

  • Has generalized epilepsy (e.g., Lennox-Gastaut, Juvenile Myoclonic epilepsy, Absence, etc).
  • Has had status epilepticus (other than simple partial status epilepticus) within the 12 months prior to Screening or during the Baseline Phase.
  • Has a history of innumerable seizures within the 12 months prior to Screening where the individual seizures cannot be counted.
  • Has a history of pseudo seizures, non-epilepsy events or any other type of psychogenic seizures that could be confused with seizures.
  • Acute Urinary Retention (treated or untreated) within 6 months of screening or an episode of Acute Urinary Retention (treated) within the last two years with symptoms within the last 6 months.
  • Screening AUA SI Score >7 (>11 for subject over 55 years old).
  • Flowmetry Peak Flow < 15mL/sec out of a urine volume void of 150mL (<11 mL/sec for subject over 55 years old) at Screening.
  • PVR >125mL or >40% functional residual volume at Screening.
  • Prior history of administration of Botox® within genitourinary system.
  • Prior history or any type of medical or surgical therapy for urinary incontinence.
  • Prior history of treated or untreated, bladder, prostate, uterine or cervical cancer.
  • Use of sildenafil, tadalafil, vardenafil or other PDE-5 inhibitors within 2 weeks of study start.
  • Use of α-adrenoreceptor antagonists within 2 weeks of study start.
  • Has had previous exposure to ezogabine/retigabine.
  • Is currently or has been abusing substance(s) or any medications in the 12 months prior to Screening.
  • Has taken an investigational drug, or used an investigational device, within the previous 4 weeks prior to Screening or plans to take another investigational drug anytime during the study.
  • Is currently following or planning to follow the ketogenic diet.
  • Has been treated with felbamate or vigabatrin within the past 6 months prior to Screening; if a subject has been previously treated with vigabatrin, a visual perimetry test prior to screening (or within the past 6 months) must show normal visual fields or no worsening of recognized visual field abnormalities as compared with prior to vigabatrin treatment.
  • Use of CNS-active medication (other than concomitant AED therapy), unless subjects had been stabilized on such medication for more than 4 weeks prior to Screening.
  • Use of herbal treatments with CNS activity within 4 weeks prior to Screening.
  • Current use of any prohibited concomitant medication as indicated in Section 5.7.2.
  • Is planning surgery to control seizures during the study.
  • Is suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that, in the investigator's judgment, are likely to interfere with the objectives of the study.
  • Has any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs.
  • Has an average QTc ≥ 450 msec or ≥ 480 msec for subjects with Bundle Branch Block at the time of Screening.

Note: If the initial electrocardiogram (ECG) at Screening indicates a corrected QT (QTc) interval outside these limits, two further ECGs should be performed and the average QTc value of these triplicate ECGs calculated. If the average value exceeds the stated limits, the subject is not eligible.

  • Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than one lifetime suicide attempt.
  • Has positive test results for hepatitis B surface antigen, positive hepatitis C virus, or human immunodeficiency virus (HIV)-1 or -2 at Screening.
  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: NCT01607346

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United States, Arkansas
GSK Investigational Site Recruiting
Little Rock, Arkansas, United States, 72205
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, Maryland
GSK Investigational Site Completed
Bethesda, Maryland, United States, 20817
United States, Pennsylvania
GSK Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
United States, Texas
GSK Investigational Site Not yet recruiting
Arlington, Texas, United States, 76017
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
France
GSK Investigational Site Recruiting
Dijon, France, 21000
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
GSK Investigational Site Recruiting
Rennes Cedex, France, 35033
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01607346     History of Changes
Other Study ID Numbers: 116158
Study First Received: May 17, 2012
Last Updated: June 19, 2014
Health Authority: Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
France: AFSSAPS: Agence Française de Sécurité Sanitaire des Produits de Santé
Poland: URZ.D REJESTRACJI PRODUKTÓW LECZNICZYCH, WYROBÓW MEDYCZNYCH I PRODUKTÓW BIOBÓJCZYCH,CEBK
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Urinary Retention

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
D 23129
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014