Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects (>= 12 Years Old) With POS or LGS

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01668654
• Date of registration: 17/05/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects (>= 12 Years Old) With POS or LGS
• 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)
• Date of first enrolment: September 4, 2012
• Target sample size: 4
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01668654
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- Investigator and caregiver consider it beneficial for the patient to continue
treatment with retigabine/ezogabine

- 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

- Subject is living with his/her custodial parent(s) or legal guardian(s) and has
contact with them on a daily basis

- 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

Exclusion Criteria:

- Has insufficient ability to articulate the presence or absence of urinary tract
symptoms

- 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

- Has a urine sample with: 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

- Has a blood sample with: 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

- 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%

- Has presence of clinically significant cardiac arrhythmias

- Has any abnormality on 12-lead ECG 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

- Has a history of one or more renal calculi

- Has disturbances of micturition or known urinary obstructions, including renal calculi

- Has a documented anatomical stricture or other anatomical abnormality of the urinary
tract system that has the potential to interfere with urinary flow

- Has experienced clinically significant urinary retention and/or required urinary
catheterization in the preceding 6 months

- Has experienced 2 or more objectively documented urinary tract infections in the
preceding 12 months

- Has a history of inadequate fluid intake and clinically significant dehydration in the
preceding 6 months

- Within the preceding month, has taken anti-cholinergic medication on an ongoing basis

- Has active suicidal plan/intent or has had active suicidal thoughts in the past 6
months or has history of suicide attempt in the last 2 years or more than one lifetime
suicide attempt

- Is planning surgery or implantation of a vagus nerve stimulator to control seizures
during the study

- Is currently or has been abusing substance(s) or any medications in the 12 months
prior to study entry

- Has taken an investigational drug (exception retigabine/ezogabine), or used an
investigational device, within the previous 30 days prior, or plans to take an
investigational drug anytime during the study

- Females who are lactating or are pregnant

- Unwillingness or inability to follow the procedures outlined in the protocol

- The subject is felt, by the investigator, to be unsuitable for inclusion in the study

- Children in care



Age minimum: 12 Years
Age maximum: 29 Years
Gender: All

Health Condition(s) or Problem(s) studied

Epilepsy

Intervention(s)

Drug: retigabine/ezogabine

Primary Outcome(s)

Change From Baseline in the Hematocrit Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in the Red Blood Cell Count Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Albumin, Total Protein, Hemoglobin, and Mean Corpuscle Hemoglobin Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Body Temperature at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in ALT, ALP, AST, CK, and LDH Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, and Red Cell Distribution Width (RDW) Percentages at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, and White Blood Cell Count Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Number of Participants With Abnormal Clinically Significant ECG Findings Based on Investigator Judgment at Anytime During the Study [Time Frame: Eligibility Assessment and EW Visit]

Change From Baseline in Electrocardiogram (ECG) at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), EW Visit (up to 178 days)]

Change From Baseline in the BUN/Creatinine and the Urine Albumin/Creatinine Ratios at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Body Height at Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Changes From Baseline in Behaviour as Measured by the Child Behavior Checklist (CBCL) at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1) up to 178 days]

Change From Baseline in Mean Corpuscle Hemoglobin at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Number of Participants With AEs Leading to Withdrawal [Time Frame: From the start of study medication until the end of the Follow-Up Visit (up to 178 days)]

Change From Baseline in SBP and DBP at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Number of Participants With Sexual Maturation Based on the Tanner Stage I to Stage V of Puberty in Participants <=18 Years Old Throughout the Study [Time Frame: Eligibility Assessment (Visit 1) and EW Visit]

Changes From Baseline in Learning as Measured by the Wide Range Assessment of Memory and Learning , 2nd Edition (WRAML2) at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1) up to 178 days]

Change From Baseline in Body Weight at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Creatinine, Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Uric Acid, and Urine Creatinine Concentration Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Thyroid Stimulating Hormone (TSH) and Urine Albumin Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Number of Participants (Par.) With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period [Time Frame: From the start of study medication until the end of Follow-Up (up to 178 days)]

Number of Participants With Vital Signs Outside the Pre-determined Clinically Important Findings or Outside the Normal Ranges at Any Time During the Study [Time Frame: Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Calcium, Carbon Dioxide Content/Bicarbonate, Chloride, Cholesterol, Glucose, Magnesium, Inorganic Phosphorus, Potassium, Sodium, and Urea/BUN Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Heart Rate at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Changes From Baseline in Cognition as Measured by the Leiter-R at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1) up to 178 days]

Number of Days of Exposure to Retigabine/Ezogabine TID by Individual Participant [Time Frame: Treatment Phase plus Taper Phase (up to 97 days)]

Number of Partcipants With Hematology, Chemistry and Urinalysis Parameters Outside the Normal Ranges and Pre-determined Clinically Important Ranges [Time Frame: Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in Body Mass Index (BMI) at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Change From Baseline in the Mean Corpuscle Volume and Mean Platelet Volume Measurements at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 4, Visit 5, Visit 6, Visit 7, Early Withdrawal (EW) Visit, and Follow-Up (FU) Visit (up to 178 days)]

Changes From Baseline in Bladder Volume as Assessed by the Post Void Residual (PVR) Ultrasound at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1), Visit 6, EW Visit]

Secondary Outcome(s)

Apparent Clearance (CL/F) Following Oral Administration of Retigabine/Ezogabine at Indicated Time Points [Time Frame: Eligbility Assessment (Visit 1), up to 178 days]

Change From Baseline in Child Health Status as Measured by the Child Health Questionnaire (CHQ) in Participants <18 Years Old at the Indicated Time Points [Time Frame: Baseline, Eligibilty Assessment (Visit 1), EW Visit and FU Visit (up to 178 days)]

Area Under the Plasma Concentration-time Curve (AUC) Following Oral Administration of Retigabine/Ezogabine at the Indicated Time Points [Time Frame: Eligibility Assessment (Visit 1) up to 178 days]

Number of Participants Who Were Responders During the Treatment Period [Time Frame: Eligibility Assessment (Visit 1) up to 178 days]

Clinical Global Impression- Improvement (CGI-I) Assessment at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1) up to 178 days]

Clinical Global Impression-Severity of Illness (CGI-S) Assessment at the Indicated Time Points [Time Frame: Baseline, Eligibility Assessment (Visit 1) up to 178 days]

Percent Change From Baseline in the Seizure Frequency at the Indicated Time Points [Time Frame: Basline, Eligibility Assessment (Visit 1) up to 178 days]

Secondary ID(s)

113388

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bausch Health Americas, Inc.

Results

• Results available: Yes
• Date Posted: 04/08/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01668654