Trial Outcomes & Findings for Long-term, Open-label Safety Extension Study of Retigabine/Ezogabine in Pediatric Subjects (>= 12 Years Old) With POS or LGS (NCT NCT01668654)

NCT ID: NCT01668654

Last Updated: 2020-10-30

Results Overview

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of the study medication, whether or not considered related to the study medication. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Please refer to the AE/SAE module for a list of non-serious AEs and SAE.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 4 participants
• Primary outcome timeframe: From the start of study medication until the end of Follow-Up (up to 178 days)
• Results posted on: 2020-10-30

Participant Flow

Participants (par.) aged 12 years or older, who had participated in a previous parent study GSK113284 (NCT014945840) evaluating Retigabine/Ezogabine in the treatment of partial onset seizures or seizures comprising Lennox-Gastaut syndrome, were enrolled in this open-label extension study.

Eligible par. began the Treatment Period at the eligibility assessment Visit followed by a 3-week Taper Phase, and a Follow-Up Visit within 3 days from the end of the Taper Phase. The study was prematurely discontinued after enrolling only 4 of the planned 500 par.

Participant milestones

Measure	Retigabine/Ezogabine TID Participants (par.) received retigabine/ezogabine as immediate release (IR) tablets three times a day (TID) as add-on therapy. Six dose strengths (25 milligrams(mg)/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg per day (mg/day) (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.
Overall Study STARTED	4
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	Retigabine/Ezogabine TID Participants (par.) received retigabine/ezogabine as immediate release (IR) tablets three times a day (TID) as add-on therapy. Six dose strengths (25 milligrams(mg)/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg per day (mg/day) (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.
Overall Study Study Closed/Terminated	3
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Retigabine/Ezogabine TID n=4 Participants Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.
Age, Continuous	15.3 Years STANDARD_DEVIATION 1.50 • n=93 Participants
Sex: Female, Male Female	1 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants
Race/Ethnicity, Customized White/Caucasian/European Heritage	4 Participants n=93 Participants

PRIMARY outcome

Timeframe: From the start of study medication until the end of Follow-Up (up to 178 days)

Population: All Subjects Population: all participants who enrolled in the study.

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of the study medication, whether or not considered related to the study medication. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Please refer to the AE/SAE module for a list of non-serious AEs and SAE.

Outcome measures

Measure	Retigabine/Ezogabine TID n=4 Participants Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.
Number of Participants (Par.) With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period Any AE	4 Participants
Number of Participants (Par.) With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period Any SAE	0 Participants

PRIMARY outcome

Timeframe: From the start of study medication until the end of the Follow-Up Visit (up to 178 days)

Population: All Subjects Population

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of the study medication, whether or not considered related to the study medication. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or is a congenital anomaly or birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. Please refer to the AE/SAE module for a list of non-serious AEs and SAE.

Outcome measures

Measure

Retigabine/Ezogabine TID n=4 Participants Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.

Number of Participants With AEs Leading to Withdrawal

0 Participants

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Vital sign assessment included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and body temperature measurements. SBP, DBP and heart rate were measured at the following Visits: 1, 4, 5, 6, 7, EW and the FU Visit after the participants were in the seated position for 5 minutes.

Outcome measures

Measure

Retigabine/Ezogabine TID n=4 Participants Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.

Number of Participants With Vital Signs Outside the Pre-determined Clinically Important Findings or Outside the Normal Ranges at Any Time During the Study

0 Participants

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Vital sign assessment included SBP and DBP measurements. SBP and DBP were measured at the following Visits: 1, 4, 5, 6, 7, EW, and the FU Visit after the participant was in seated position for 5 minutes. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Vital sign assessment included heart rate measured at the following Visits: 1, 4, 5, 6, 7, EW, and the FU Visit after the participant was in seated position for 5 minutes. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Vital sign assessment included body temperature measurements at the following Visits: 1, 4, 5, 6, 7, EW, and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Body height was measured without shoes and wearing light clothing at the following Visits: 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Body weight was measured without shoes and wearing light clothing at the following Visits: 1, 4, 5, 6, 7, EW and FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

BMI is calculated as weight in kilograms (kg) divided by the square of their height in metres (m^2). BMI was measured at the following Visits: 1, 4, 5, 6, 7, EW and FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline, Eligibility Assessment (Visit 1), EW Visit (up to 178 days)

Population: All Subjects Population

The 12-lead ECG was recorded in a supine position at the Eligibility Assessment Visitand the EW Visit after having kept a participant at rest in this position for 10 minutes. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Eligibility Assessment and EW Visit

Population: All Subjects Population

The 12-lead ECG was recorded in a supine position at the Eligibility Assessment Visit andthe EW Visit after having kept a participant at rest in this position for 10 minutes. Abnormal findings were analyzed as clinically significant (CS) and not clinically significant (NCS). The study investigator judged the ECG abnormailities as CS or NCS.

Outcome measures

Measure

Retigabine/Ezogabine TID n=4 Participants Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.

Number of Participants With Abnormal Clinically Significant ECG Findings Based on Investigator Judgment at Anytime During the Study

0 Participants

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Alanine amino transferase (ALT), alkaline phosphotase (ALP), aspartate amino transferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Albumin, total protein, hemoglobin, and mean corpuscle hemoglobin concentration parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Blood Urea Nitrogen (BUN)/Creatinine and Urine Albumin/Creatinine were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Calcium, carbon dioxide content/bicarbonate, chloride, cholesterol, glucose, magnesium, inorganic phosphorus, potassium, sodium, and urea/BUN parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Creatinine, direct bilirubin, indirect bilirubin, total bilirubin, uric acid, and urine creatinine concentration parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included measurements of endocrine and urinalysis parameters. TSH and urine albumin parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Basophils, eosinophils, lymphocytes, monocytes, platelet count, segmented neutrophils, total neutrophils (Total absolute neutrophil count- total ANC), and white blood cell count parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Basophils, eosinophils, lymphocytes, monocytes, segmented neutrophils, total neutrophils and red cell distribution width (RDW) parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Hematocrit was measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Mean corpuscle volume and mean platelet colume parameters were measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. Mean corpuscle hemoglobin was measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessments included hematology, chemistry and urinalysis parameters. The red blood cell count was measured at Visits 1, 4, 5, 6, 7, EW and the FU Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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)

Population: All Subjects Population

Clinical laboratory assessment included hematology, chemistry and urinalysis parameters. Clinical laboratory parameters were measured at Visit 1, 4, 5, 6, 7, EW and FU Visit. Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline, Eligibility Assessment (Visit 1), Visit 6, EW Visit

Population: All Subjects Population

The PVR urine test measured the amount of urine left in the bladder after urination. The PVR bladder ultrasound was performed by an urologist, a qualified technician or by an appropriately trained qualified study nurse at Visits 1, 6, and the EW Visit. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose values. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline, Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

he Leiter International Performance Scale or simply Leiter is an intelligence test for children and adolescents, with norms ranging from 2 to 20 years. For all ages, it yields an intelligence quotient (IQ) and a measure of logical ability. It is comprised of ten subtests, seven of which were relevant to the 12-18 years age group. The administration time was approximately 40 minutes. During the study, only the parent/caregiver completed this questionnaire while the participants were within the age range (i.e. <20 years). Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). The parent study did not measure baseline cognition, behavior, and learning so changes from baseline were not available for participants in this study.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline, Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

The CBCL is a widely used parent report questionnaire identifying behavioural and emotional problems in children. The checklist is comprised of a number of statements about the child's behavior, e.g. acts too young for his/her age. Responses were recorded on a likert scale: 0 = not true, 1 = somewhat or sometimes true, 2 = very true or often true. The preschool checklist contained 100 questions and the school-age checklist contained 120 questions. During the study, only the parent/caregiver completed this questionnaire while the participants were within the age range (i.e. <18 years). Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). The parent study did not measure baseline cognition, behavior, and learning so changes from baseline were not available for participants in this study.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline, Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

The WRAML2 is a standardized test that measures an individual's memory functioning. It evaluates both visual and verbal, immediate and delayed memory ability along with the acquisition of new learning. The WRAML2 core battery is composed of two verbal, two visual, and two attention concentration subtests, yielding a verbal memory index, a visual memory index and an attention-concentration index. Together, these tests yield the general memory index. The administration time is approximately 40 minutes. During the study, this test was administered if the participant was within the age range (i.e. >9 years). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). The parent study did not measure Baseline cognition, behavior, and learning so changes from Baseline were not available for participants in this study.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Eligibility Assessment (Visit 1) and EW Visit

Population: All Subjects Population

The number of participants who advanced a stage between the eligibility visit and the EW Visit was recorded. Tanner stage I is defined as no pubic hair at all (prepubertal Dominic state); stage II is defined as a small amount of long, downy hair with slight pigmentation at the base of the penis and scrotum (males) or on the labia majora (females); stage III is defined as when the hair becomes more coarse and curly, and begins to extend laterally; stage IV is defined as adult-like hair quality, extending across pubis but sparing medial thighs; and stage V is defined as when the: hair extends to medial surface of the thighs. The investigator assessed the participant's sexual development in participants <18 years old based on the Tanner Stages of Puberty.

Outcome measures

Measure	Retigabine/Ezogabine TID n=4 Participants Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.
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 Stage I to Stage II	0 Participants
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 Stage II to Stage III	0 Participants
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 Stage III to Stage IV	0 Participants
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 Stage IV to Stage V	2 Participants
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 Stage V	2 Participants

PRIMARY outcome

Timeframe: Treatment Phase plus Taper Phase (up to 97 days)

Population: All Subjects Population

Total number of days each participant was exposed to Retigabine/Ezogabine are recorded here.

Outcome measures

Measure	Retigabine/Ezogabine TID n=4 Participants Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability). Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.
Number of Days of Exposure to Retigabine/Ezogabine TID by Individual Participant Participant 1	133 Days
Number of Days of Exposure to Retigabine/Ezogabine TID by Individual Participant Participant 2	213 Days
Number of Days of Exposure to Retigabine/Ezogabine TID by Individual Participant Participant 3	196 Days
Number of Days of Exposure to Retigabine/Ezogabine TID by Individual Participant Participant 4	166 Days

SECONDARY outcome

Timeframe: Basline, Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

The percentage reduction from Baseline in the seizure frequency was summarized using descriptive statistics. The frequencies and percentages were computed for a reduction in seizure frequency of >50% as well as for a 100% reduction (seizure-free). Increases of >50% in seizure frequency was also summarized. The percentage of seizure-free days wasere also analyzed. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

A ''responder'' is defined as >50% reduction from Baseline in the seizure frequency. Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

The Clinical Global Impression (CGI) scale provided an overall clinician-determined summary measure. It had 2 components: the CGI-Severity of Illness (CGI-S) scale and the CGI- Improvement (CGI-I) scale which rated the change from Baseline. The CGI-I scale scores range from 0 to 7 and are interpreted as 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

The Clinical Global Impression (CGI) scale provided an overall clinician-determined summary measure. It had 2 components: the CGI-Severity of Illness (CGI-S) scale and the CGI-Improvement (CGI-I) scale which rated the change from Baseline. The CGI-S was a 7-point scale that required the investigator to rate the severity of the participant's epilepsy relative to the investigator's past experience with other participants with the same diagnosis. The CGI-S scale scores range from 0 to 7 and are interpreted as 0=not assessed, 1=normal, 2=borderline, 3=mild, 4=moderate, 5=marked, 6=severe, 7=extremely severe. Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Eligibilty Assessment (Visit 1), EW Visit and FU Visit (up to 178 days)

Population: All Subjects Population

The CHQ comprises scales specifically developed for children and adolescents aged five years and older. The CHQ assesses a child's physical, emotional, and social well-being from the perspective of a parent or guardian. The questionnaire was completed by a parent/caregiver and administration time was approximately 30 minutes. The parent/caregiver completed this questionnaire while the participant was within the age range (i.e. <18 years). Baseline was the first pre-Retigabine assessment conducted in the parent study GSK113284 (NCT014945840). Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Eligibility Assessment (Visit 1) up to 178 days

Population: All Subjects Population

AUC is defined as the area under the plasma drug concentration-time curve, reflects the actual body exposure to drug after administration of a dose of the drug and is expressed in milligram*hour per Liter (mg*h/L). Blood samples for population PK analysis of retigabine/ezogabine were taken at clinic visits where routine clinical laboratory samples were also taken. Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Eligbility Assessment (Visit 1), up to 178 days

Population: All Subjects Population

Blood samples for population pharmacokinetic analysis of retigabine/ezogabine were taken at clinic visits where routine clinical laboratory samples were also taken. CL/F, where CL is the calculated as dose/AUC and F is the oral bioavailability of the drug. Because the study was terminated prematurely and the sample size is small, summary statistics were not compiled

Outcome measures

Outcome data not reported

Adverse Events

Retigabine/Ezogabine TID

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Retigabine/Ezogabine TID n=4 participants at risk Par. received retigabine/ezogabine as IR tablets TID as add-on therapy. Six dose strengths (25 mg/50 mg/100 mg/200 mg/300 mg/400 mg) were used. Doses may have been titrated no more frequently than once per week. Par. dose was adjusted as needed (e.g. based on: weight change due to increasing age and growth, efficacy or tolerability) over the course of this long-term open-label extension study. Physicians used their clinical judgment in making dose adjustments. Maximum doses allowed in the study were 900 mg/day (\>50 kilogram (kg) weight) or 450 mg/day (30 to 50 kg weight) for par. aged \<16 years old and the maximum doses allowed were 1200 mg/day (\>50 kg weight) or 600 mg/day (30 to 50 kg weight) for par. aged \>=16 years old.
Gastrointestinal disorders Vomiting	25.0% 1/4 • Non-serious adverse event (AE) and serious adverse events (SAE) were collected from the start of study treatment until the Follow-Up contact (Up to 178 days) SAEs and non-serious AEs are reported for members of the Safety Population, comprised of participants who took at least one dose of investigational product after being enrolled into the study.
Skin and subcutaneous tissue disorders Ingrowing nail	25.0% 1/4 • Non-serious adverse event (AE) and serious adverse events (SAE) were collected from the start of study treatment until the Follow-Up contact (Up to 178 days) SAEs and non-serious AEs are reported for members of the Safety Population, comprised of participants who took at least one dose of investigational product after being enrolled into the study.
Nervous system disorders Migraine	25.0% 1/4 • Non-serious adverse event (AE) and serious adverse events (SAE) were collected from the start of study treatment until the Follow-Up contact (Up to 178 days) SAEs and non-serious AEs are reported for members of the Safety Population, comprised of participants who took at least one dose of investigational product after being enrolled into the study.
Infections and infestations Viral infection	25.0% 1/4 • Non-serious adverse event (AE) and serious adverse events (SAE) were collected from the start of study treatment until the Follow-Up contact (Up to 178 days) SAEs and non-serious AEs are reported for members of the Safety Population, comprised of participants who took at least one dose of investigational product after being enrolled into the study.
General disorders Pyrexia	25.0% 1/4 • Non-serious adverse event (AE) and serious adverse events (SAE) were collected from the start of study treatment until the Follow-Up contact (Up to 178 days) SAEs and non-serious AEs are reported for members of the Safety Population, comprised of participants who took at least one dose of investigational product after being enrolled into the study.
Nervous system disorders Headache	25.0% 1/4 • Non-serious adverse event (AE) and serious adverse events (SAE) were collected from the start of study treatment until the Follow-Up contact (Up to 178 days) SAEs and non-serious AEs are reported for members of the Safety Population, comprised of participants who took at least one dose of investigational product after being enrolled into the study.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER