Long-term Open-label Evaluation of Retigabine in Pediatric Subjects with Epilepsy

• Register: EUCTR
• Last refreshed on: 20 March 2012
• Main ID: EUCTR2010-020154-33-Outside-EU/EEA
• Date of registration: 09/03/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline R&D Limited
• Public title: Long-term Open-label Evaluation of Retigabine in Pediatric Subjects with Epilepsy
• Scientific title: RTG113388, a Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects with Partial Onset Seizures(=12 years old) and Subjects with Lennox-Gastaut Syndrome (=12 years old) - Long-term Open-label Safety Extension Study of Retigabine/Ezogabine in subjects >=12yrs with POS/LGS
• Target sample size: 500
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020154-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

United States

Contacts

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development

Key inclusion & exclusion criteria

Inclusion criteria:
1. The subject has participated in either a Phase II or Phase III retigabine/ezogabine clinical trial evaluating partial onset seizures or seizures comprising Lennox-Gastaut syndrome and met the requirements defined in the parent study to transition into the
open-label extension study.
2. The investigator and caregiver consider it beneficial for the subject to receive retigabine/ezogabine.
3. Female subjects of child-bearing potential (after menarche) must either not be sexually active or must be practicing an acceptable method of contraception (documented in the medical chart) from two weeks prior to administration of study medication and for 28 days after completion or premature discontinuation from the study (see Appendix 2).
4. Subject is living with his/her custodial parent(s) or legal guardian(s) and has contact with them on a daily basis.
5. Written informed consent is obtained from the subjects parent/guardian and accompanying assent from subject. The subject, and/or his/her custodial parents(s) or legal guardian(s) have the ability to comprehend the key components of the informed
consent form.
Are the trial subjects under 18? yes
Number of subjects for this age range: 500
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Has insufficient ability to articulate the presence or absence of urinary tract symptoms.
2. Has experienced an adverse event, clinically significant laboratory abnormality or was discontinued from the parent study due to a reason that in the investigator’s judgment would preclude enrollment to the study.
3. Has a urine sample with any of the following at the Eligibility Assessment Visit, confirmed by repeat sample:
- Urine specific gravity >1.035
- Urine pH <4.6 or >8.0
- =2+ proteinuria
- Casts or crystals (any type)
- >5 RBC/HPF, unrelated to menses (i.e. this criterion will not apply if sample taken within 5 days of menses, in female subjects that have experienced menarche). Note: The above criterion applies to urine samples analyzed by the central laboratory and not to urine dipstick testing.
4. Has a blood sample with any of the following at the Eligibility Assessment Visit, confirmed by repeat sample:
– BUN >21 mg/dl for 12 year old, or >25 mg/dl for >12 year old.
– Creatinine >1.03 mg/dl (F), or >1.3 mg/dl (M)
– Uric acid >7.5 mg/dl (F), or >8.5 mg/dl (M)
– Chloride >108 mEq/L
– Parameters for calcium, inorganic phosphorous or CO2 that are clinically significant as judged by the investigator.
5. Has presence of clinically significant hepatic laboratory values: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2x upper limit of normal (ULN); alkaline phosphatase and bilirubin =1.5xULN (isolated bilirubin >1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
6. Has presence of clinically significant cardiac arrhythmias.
7. Has any abnormality on 12-lead ECG at the Eligibility Assessment Visit which is clinically significant in the opinion of the investigator, or has a corrected QT interval (using either Bazett’s or Fridericia’s) >500msec ( >530 msec for subjects with Bundle Branch Block), uncorrected QT interval >600msec, or change from baseline
QTc >60msec. Note: If the ECG indicates a prolonged QTc interval outside these limits, two further ECGs should be performed and the average QTc value of these triplicate ECGs will be calculated. If the average value exceeds the stated limits, the subject is not eligible.
8. Has a history of one or more renal calculi.
9. Has disturbances of micturition or known urinary obstructions, including renal calculi, (incontinence concomitant with seizures is not considered a disturbance of micturition).
10. Has a documented anatomical stricture or other anatomical abnormality of the urinary tract system that has the potential to interfere with urinary flow.
11. Has experienced clinically significant urinary retention and/or required urinary catheterization in the preceding 6 months.
12. Has experienced 2 or more objectively documented urinary tract infections in the preceding 12 months.
13. Has a history of inadequate fluid intake and clinically significant dehydration in the preceding 6 months.
14. Within the preceding month, has taken anti-cholinergic medication on an ongoing basis.
15. 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.
16. Is planning surgery or implantation of a vagus nerve stimulator to control seizures during the study.
17. Is currently or has been abusing substance(s) or any medications in the 12 months prior to the El

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Uncontrolled partial onset seizures or Lennox Gastaut Syndrome
MedDRA version: 14.1 Level: PT Classification code 10061334 Term: Partial seizures System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 14.1 Level: PT Classification code 10048816 Term: Lennox-Gastaut syndrome System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: RETIGABINE/EZOGABINE
Product Code: GW582892
Pharmaceutical Form: Tablet
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Current Sponsor code: GW582892
Other descriptive name: EZOGABINE (US ONLY)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Potiga
Product Name: RETIGABINE/EZOGABINE
Product Code: GW582892
Pharmaceutical Form: Tablet
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Current Sponsor code: GW582892
Other descriptive name: EZOGABINE (US ONLY)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Current Sponsor code: GW582892
Other descriptive name: EZOGABINE (US ONLY)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Current Sponsor code: GW582892
Other descriptive name: EZOGABINE (US ONLY)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Current Sponsor code: GW52892
Other descriptive name: EZOGABINE (US only)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Product Name: RETIGABINE/EZOGABINE
Product Code: GW582892
Pharmaceutical Form: Tablet
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Current Sponsor code: GW582892
Other descriptive name: EZOGABINE (US ONLY)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): • Incidence of adverse events (AEs) and serious adverse events (SAEs).
• Incidence of AEs leading to withdrawal.
• Incidence of vital signs outside normal ranges and pre-determined clinically important ranges.
• Summary and change from baseline in vital signs (including blood pressure, heart rate) and height, weight, and body mass index.
• Summary and change from baseline of electrocardiogram (ECG) parameters.
• Summary of ECG assessment and interpretation of clinical significance based on investigator judgment.
• Change from baseline in hematology, chemistry and urinalysis parameters.
• Incidence of hematology, chemistry and urinalysis parameters outside normal ranges and pre-determined clinically important ranges.
• Change from baseline in bladder volume as assessed by the post-void residual (PVR) ultrasound.
• Changes from baseline in cognition, behavior and learning, as measured by the Leiter-R, Child Behavior Checklist, and Wide Range Assessment of Memory and Learning 2nd Edition, respectively. Note: Lennox-Gastaut Syndrome subjects will
be assessed for behavior and where mental disability is not prohibitive, for cognition and learning.
• Summary of sexual maturity over time based on the Tanner Stages of Puberty in subjects <18 years old.
• Time to withdrawal.

Timepoint(s) of evaluation of this end point: Overall and at selected time periods.

Main Objective: To evaluate the long-term safety and tolerability of retigabine/ezogabine as adjunctive treatment in subjects with either partial onset seizures (12 to <18 years old) or Lennox-Gastaut Syndrome (12 to <30 years old) who have participated in a previous (“parent”) study.

Secondary Objective: To explore the long-term efficacy of retigabine/ezogabine as adjunctive treatment in subjects with either partial onset seizures (12 to <18 years old) or Lennox-Gastaut Syndrome (12 to <30 years old) who have participated in a previous (“parent”) study.
To evaluate the population pharmacokinetics of retigabine/ezogabine as adjunctive treatment in subjects with either partial onset seizures (12 to <18 years old) or Lennox-Gastaut Syndrome (12 to <30 years old) who have participated in a previous (“parent”) study.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Overall and at selected time periods.
During the first year of the study, pharmacokinetics (PK) blood samples will be collected at 1, 3, 6 and 12 months and from Year 2, every 4 months.

Secondary end point(s): • Percent change from baseline in seizure frequency and percentage of responders (defined as >50% reduction from baseline in seizure frequency).
• Clinical Global Impression-Improvement (CGI-I) and Severity (CGIS).
• Summary of and change from baseline in child health status as measured by the Child Health Questionnaire in subjects <18 years old.
• During the first year of the study, pharmacokinetics (PK) blood samples will be collected at 1, 3, 6 and 12 months and from Year 2, every 4 months.

Secondary ID(s)

RTG113388

Source(s) of Monetary Support

GlaxoSmithKline R&D Limited