EpilepsyPhase 2NCT01494584

Study in Pediatric Subjects With Epilepsy

A Phase 2 study testing ezogabine/retigabine in people with Epilepsy, run by GlaxoSmithKline at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This is an open-label study to evaluate the pharmacokinetics, safety and tolerability of ezogabine/retigabine in subjects aged 12 years to less than 18 years with uncontrolled partial onset seizures or Lennos-Gastaut syndrome. Read more about this study

Who is it for?: Ages 12 to 17 years
Conditions the study is for: Epilepsy
What is being tested?: ezogabine/retigabine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 4 sitesUnited States
Study dates: 25 Jul 2012to 29 Apr 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Between 12 and 18 years of age.
Diagnosis of uncontrolled partial onset seizures (with or without secondarily generalized seizures) or Lennox-Gastaut syndrome.
Taking between one and three antiepileptic drugs.
Able to swallow tablets.
Females must be of : (1) Non-childbearing potential or (2) Child-bearing potential and agrees to use acceptable contraception.

Who cannot join

Epilepsy secondary to progressive cerebral disease, tumor or any progressive neurodegenerative disease.
History of status epilepticus in the last six months.
Currently treated with felbamate or has been treated with vigabatrin within the past 6 months.
Following the ketogenic diet.
Suicidal intent or history of suicide attempt in the last 2 years.
Elevated liver enzymes or abnormal kidney function.

Show all 15Show fewer

Current disturbance of micturition or known urinary obstructions.
History of vesicoureteric reflux.
Abnormal post-void residual bladder ultrasound.
Urinary retention and/or required urinary catheterization in the preceding 6 months.
Abnormal urine sample at screening/.baseline.
Abnormal blood sample at screening.
Clinically significant arrhythmias.
Abnormal ECG at screening.
BMI lower than the 10th percentile for age and gender or subject weighs less than 30kg.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

GSK Investigational Site
Dallas, Texas, 75230-2507
GSK Investigational Site
Los Angeles, California, 90027
GSK Investigational Site
Memphis, Tennessee, 38105
GSK Investigational Site
Wellington, Florida, 33414

Other trials in United States

About this study

Official title: Open-label, Multiple Dose Study to Evaluate the Parmacokinetics, Safety and Tolerability of Ezogabine/Retigabine as Adjunctive Treatment in Subjects Aged From 12 Years to Less Than 18 Years With Partial Onset Seizures or Lennox-Gastaut Syndrome

Conditions: Epilepsy
Being tested: ezogabine/retigabine
Medical subject headings: Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ezogabine/retigabineDrug
ezogabine dose escalation

Study groups in NCT01494584
Study group	Role	What they receive
ezogabine/retigabine	Experimental	ezogabine dose escalation Receives: Drug: ezogabine/retigabine

What is being measured

The primary outcome is the main question the study is designed to answer.

The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine
The steady state pharmacokinetic profile following oral administration of ezogabine/retigabine included determining the area under the curve over the dosing interval (AUC[0-tau]). The area under the plasma concentration-time curve over the dosing interval (AUC[0-tau]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate AUC(0-tau).
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Apparent Clearance (CL/F) Following Oral Administration of Ezogabine/Retigabine
Clearance (CL/F) is defined as dose/AUC(0-tau). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate CL/F.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine
Cmax is defined as the first occurrence of the maximum observed plasma concentration. Ctau refers to the pre-dose (trough) concentration after the dosing interval which is equal to the minimum observed concentration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate Cmax and Ctau.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine
The volume of distribution (Vd/F) is defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate the apparent volume of distribution.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35

Secondary outcomes (22)

Number of Participants With Any Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Measured: From the start of the first titration until follow-up (assessed up to 46 days)
Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus, and Urea/Blood Urea Nitrogen (BUN) at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC [Total Absolute Neutrophil Count]), Platelet Count, and White Blood Cell Count at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Hematocrit at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit. The International System of Units (SI) "Fraction of one unit (1)" is reported here.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Mean Corpuscle Hemoglobin at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Mean Corpuscle Volume at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Red Blood Cell Count at Day 7 Post Each Up-titration
Change from baseline was calculated 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 35 for up-titration to 900 mg/day dose) by subtracting the baseline value from the individual post-dose values. Baseline is defined as the Screening visit.
Measured: Baseline (Screening), Day 7, Day 21, and Day 35
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up
Urinalysis parameters analyzed included: urine occult blood (UOB), urine glucose (UG), urine ketones (UK), and urine protein (UP). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test provides results in a semi-quantitative manner, and results can be read as negative (Neg), Trace, and 80, indicating proportional concentrations in the urine sample. Urinalysis parameters were assessed at Titration 1 (T1; 300 mg/day), Titration 2 (T2; 450 mg/day), Titration 3 (T3; 600 mg/day), Titration 4 (T4; 750 mg/day), and Titration 5 (T5; 900 mg/day).
Measured: Screening, Day 1 (D1), Day 7 (D7), Day 14 (D14), Day 21 (D21), Day 28 (D28), Day 35 (D35), and at the Follow-up Visit (up to Day 46)
Percent Change From Baseline in 28-day Seizure Frequency Rate
Participants or their caregivers recorded the number of seizures experienced by the participant, by seizure type (e.g., simple partial seizure [seizure that affects only a small region of the brain; consciousness is unaffected], complex partial seizure [seizure associated with unilateral cerebral hemisphere involvement and causing impairment of awareness or responsiveness], etc.), as well as by duration of episodes of innumerable seizure activity, in their daily diaries during all phases of this study. Percent change from baseline is defined as 100 * (rate in a given period minus the baseline rate) / (baseline rate). baseline seizures are defined as those seizures that occurred after Screening and before the start of the treatment. Post-baseline seizures are defined as those seizures that occurred from the start of the treatment until the start of Follow-up. Seizure frequency rate was computed as: 28 * (number of seizures during given period / number of days in given period).
Measured: Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t]) for the N-acetyl Metabolite of Ezogabine/Retigabine
The area under the curve was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the plasma n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) for the N-acetyl Metabolite of Ezogabine/Retigabine
Ctau refers to the pre-dose (trough) concentration at the end of the dosing interval which is equivalent to the minimum observed concetration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess the Ctau for n-acetyl metabolite (NAMR) of ezogabine/retigabine following oral administration of ezogabine/retigabine.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Time to Maximum Concentration (Tmax) Following Oral Administration of Ezogabine/Retigabine
Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma Tmax.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Plasma Half Life at Steady State (t1/2) Following Oral Administration of Ezogabine/Retigabine
Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to assess plasma t1/2. Steady-state t1/2 is derived as (Vd/F) / (CL/F), where Vd/F is defined as the apparent volume of distribution after extravascular (e.g., oral) administration, and CL/F is defined as the apparent clearance following oral dosing.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
An ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected for heart rate (QTc intervals) was used. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). ECG parameters were assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose, and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. The number of participants with abnormal (Abn) clinically significant (CS) and not clinically significant (NCS) ECG findings was recorded. The investigator determined if an ECG finding was CS or NCS.
Measured: Baseline (Screening) and Day 7 post up-titration, up to Day 35
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
Vital sign assessment included the measurement of systolic and diastolic blood pressure at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), Day 7 pre-dose, and 3 h post dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): Day 21 pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): Day 35 pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value.
Measured: Baseline (Screening) and Day 7 post up-titration, up to Day 35
Change From Baseline in Heart Rate (HR)
Vital sign assessment included heart rate measurement and was assessed at Titration 1 (T1; 300 mg/day): Day 1 pre-dose, Day 1 at 3 hours (h), pre-dose and 3 h post-dose. Titration 2 (T2; 450 mg/day): Day 7. Titration 3 (T3; 600 mg/day): pre-dose and 3 h post-dose. Titration 3 Dose Held (T3DH): pre-dose. Titration 4 (T4; 750 mg/day): Day 7. Titration 5 (T5; 900 mg/day): pre-dose and 3 h post-dose. Measurements were taken 7 days after each up-titration (Day 7 for 300 mg/day dose; Day 14 for up-titration to 450 mg/day dose; Day 21 for up-titration to 600 mg/day dose; Day 28 for up-titration to 750 mg/day dose; Day 35 for up-titration to 900 mg/day dose). Change from baseline was calculated by subtracting the baseline value from the individual post-dose values. Baseline is defined as as the Day 1 pre-dose value.
Measured: Baseline (Screening) and Day 7 post up-titration, up to Day 35
Change From Baseline in Post Void Residual Ultrasound at Day 21
A post void residual (PVR) bladder ultrasound was carried out as a measure of bladder function. PVR was clinically indicated following the occurrence of adverse events relating to the lower urinary tract (e.g., micturition difficulties, including urinary hesitancy or urinary retention). These assessments were also repeated following drug withdrawal following such events. A prompt follow-up PVR was recommended if a high score was obtained from a participant on the Pediatric Lower Urinary Tract Symptom scale (the PLUTS scale is a clinician-rated scale used to assess lower urinary tract symptoms, including urinary retention) and if the clinician felt that the participant was at risk or had symptoms of urinary retention. PVR was measured at Day 7 of Titration 3 (600 mg/day). Baseline is defined as the Screening visit.
Measured: Screening and Day 7 of Titration 3 (Day 21)
Number of Participants With the Indicated Neurological Abnormality
Abnormal Central Nervous System (CNS) symptoms were assessed by a full and brief neurological examination. A full neurological examination included assessment of mental status, cranial nerves, gait, coordination, sensation, speech/language, muscle strength, muscle tone, and reflexes. A brief neurological examination included assessment of mental status, cranial nerves, gait, coordination, reflexes, and speech/language. Neurological parameters assessed were memory impairment, impaired intellect, decreased attention, psychomotor slowing, decreased muscle strength, hpertonia, somnolence, right and left bicpes, right and left brachioradialis, right and left knee, right and left ankle, and right and left planter response. Neurological examination was performed at Day 7 of Titration 3 (600 mg/day).
Measured: Screening and Day 7 of Titration 3 (Day 21)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Jul 201229 Apr 2013

First posted19 Dec 2011 (estimated)
Study start25 Jul 2012
Primary completion29 Apr 2013
Study completion29 Apr 2013

Why it stopped: Terminated after placing the study on hold at the request of the FDA

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for EpilepsyStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01494584
Sponsor's protocol ID: 113284
Status last verified: Nov 2020
First submitted: 1 Dec 2011
Last updated: 30 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Tompson DJ, Buraglio M, Andrews SM, Wheless JW. Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for Partial-Onset Seizures: Pharmacokinetics and Tolerability. J Pediatr Pharmacol Ther. 2016 Sep-Oct;21(5):404-412. doi: 10.5863/1551-6776-21.5.404.
PubMed 27877093

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-label, Multiple Dose Study to Evaluate the Parmacokinetics, Safety and Tolerability of Ezogabine/Retigabine as Adjunctive Treatment in Subjects Aged From 12 Years to Less Than 18 Years With Partial Onset Seizures or Lennox-Gastaut Syndrome
ClinicalTrials.gov ID: NCT01494584
Acronym / sponsor ID: 113284
Conditions: Epilepsy
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Terminated after placing the study on hold at the request of the FDA
Enrolment: 5 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Collaborators: Bausch Health Americas, Inc.
Study start: 25 Jul 2012 (actual)
Primary completion: 29 Apr 2013 (actual)
Study completion: 29 Apr 2013 (actual)
First posted: 19 Dec 2011 (estimated)
Results: Posted 4 Sep 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ezogabine/retigabine	Experimental	Drug: ezogabine/retigabineezogabine dose escalation

Who may qualify

Ages: 12 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

Between 12 and 18 years of age.
Diagnosis of uncontrolled partial onset seizures (with or without secondarily generalized seizures) or Lennox-Gastaut syndrome.
Taking between one and three antiepileptic drugs.
Able to swallow tablets.
Females must be of : (1) Non-childbearing potential or (2) Child-bearing potential and agrees to use acceptable contraception.

Key exclusion criteria (15 listed)

Epilepsy secondary to progressive cerebral disease, tumor or any progressive neurodegenerative disease.
History of status epilepticus in the last six months.
Currently treated with felbamate or has been treated with vigabatrin within the past 6 months.
Following the ketogenic diet.
Suicidal intent or history of suicide attempt in the last 2 years.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ezogabine/retigabineezogabine dose escalation	Drug	ezogabine/retigabine

Primary outcome

The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
The steady state pharmacokinetic profile following oral administration of ezogabine/retigabine included determining the area under the curve over the dosing interval (AUC[0-tau]). The area under the plasma concentration-time curve over the dosing interval (AUC[0-tau]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate AUC(0-tau).
Apparent Clearance (CL/F) Following Oral Administration of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Clearance (CL/F) is defined as dose/AUC(0-tau). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate CL/F.
Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Cmax is defined as the first occurrence of the maximum observed plasma concentration. Ctau refers to the pre-dose (trough) concentration after the dosing interval which is equal to the minimum observed concentration (Cmin) at Steady State. Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate Cmax and Ctau.
Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
The volume of distribution (Vd/F) is defined as MRT*CL/F, where MRT is the mean residence time (calculated as AUMC[0-tau]/AUC[0-tau], where AUMC[0-tau] is the area under the first moment curve determined as the area under the concentration*time versus time curve). Blood samples were collected at pre-dose and at 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35 to estimate the apparent volume of distribution.

22 secondary outcomes

Number of Participants With Any Adverse Event (AE)
Time frame: From the start of the first titration until follow-up (assessed up to 46 days)
Change From Baseline in Albumin and Total Protein at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, and Gamma Glutamyl Transferase at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Direct Bilirubin, Total Bilirubin, Creatinine, and Uric Acid at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Calcium, Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, Inorganic Phosphorus, and Urea/Blood Urea Nitrogen (BUN) at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC [Total Absolute Neutrophil Count]), Platelet Count, and White Blood Cell Count at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Hematocrit at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Mean Corpuscle Hemoglobin at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Mean Corpuscle Volume at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Change From Baseline in Red Blood Cell Count at Day 7 Post Each Up-titration
Time frame: Baseline (Screening), Day 7, Day 21, and Day 35
Number of Participants With the Indicated Urinalysis Parameter Dipstick Test Results From Screening to Follow-up
Time frame: Screening, Day 1 (D1), Day 7 (D7), Day 14 (D14), Day 21 (D21), Day 28 (D28), Day 35 (D35), and at the Follow-up Visit (up to Day 46)
Percent Change From Baseline in 28-day Seizure Frequency Rate
Time frame: Baseline (Screening) and until Follow-up or early discontinuation (assessed up to 46 days)
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Last Time of Quantifiable Concentration (AUC [0-t]) for the N-acetyl Metabolite of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) for the N-acetyl Metabolite of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Time to Maximum Concentration (Tmax) Following Oral Administration of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Plasma Half Life at Steady State (t1/2) Following Oral Administration of Ezogabine/Retigabine
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Baseline (Screening) and Day 7 post up-titration, up to Day 35
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
Time frame: Baseline (Screening) and Day 7 post up-titration, up to Day 35
Change From Baseline in Heart Rate (HR)
Time frame: Baseline (Screening) and Day 7 post up-titration, up to Day 35
Change From Baseline in Post Void Residual Ultrasound at Day 21
Time frame: Screening and Day 7 of Titration 3 (Day 21)
Number of Participants With the Indicated Neurological Abnormality
Time frame: Screening and Day 7 of Titration 3 (Day 21)

Results and safety

Results posted to the registry on 4 Sep 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ezogabine/Retigabine	5	4

Primary outcome: The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35. Geometric mean (95% Confidence Interval). Unit: Hour*Nanograms/Milliliter (h.ng/mL)

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n = 5	Regimen A: E/R 300/450 mg Then 600 mg n = 4	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n = 3
Value	1680.0 (1162.4 to 2428.2)	2558.8 (1873.4 to 3494.8)	3783.8 (1059.6 to 13512.0)

Population analysed: Pharmacokinetic Population: all participants in the All Subjects Population (defined as all participants who received at least one dose of study medication) for whom a pharmacokinetic sample was obtained and analyzed

Primary outcome: Apparent Clearance (CL/F) Following Oral Administration of Ezogabine/Retigabine

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35. Geometric mean (95% Confidence Interval). Unit: Liters/Hour

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n = 5	Regimen A: E/R 300/450 mg Then 600 mg n = 4	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n = 3
Value	178.6 (123.5 to 258.1)	234.5 (171.7 to 320.3)	237.9 (66.6 to 849.4)

Population analysed: Pharmacokinetic Population

Primary outcome: Maximum Observed Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) Following Oral Administration of Ezogabine/Retigabine

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35. Geometric mean (95% Confidence Interval). Unit: Nanograms/Milliliter (ng/mL)

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n = 5	Regimen A: E/R 300/450 mg Then 600 mg n = 4	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n = 3
Cmax	370.0 (260.9 to 524.7)	535.9 (344.4 to 833.8)	750.9 (289.8 to 1945.3)
Ctau	105.32 (58.70 to 188.98)	199.77 (140.67 to 283.72)	287.48 (44.38 to 1862.12)

Population analysed: Pharmacokinetic Population

Primary outcome: Apparent Volume of Distribution (Vd/F) Following Oral Administration of Ezogabine/Retigabine

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35. Geometric mean (95% Confidence Interval). Unit: Liters

Measure	Regimen A: Ezogabine/Retigabine (E/R) 300 mg n = 3	Regimen A: E/R 300/450 mg Then 600 mg n = 3	Regimen A: E/R 300/450/ 600/750 mg Then 900 mg n = 1
Value	1130.9 (511.1 to 2502.1)	2118.0 (539.4 to 8315.8)	1934.3 (NA to NA)

Population analysed: Pharmacokinetic Population. Only those participants available at the specified time points were analyzed.

22 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data, volunteered by the participant, discovered by the investigator, or detected by other means, were collected from the start of study treatment until the Follow-up contact (maximum of 46 days).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Regimen A: Ezogabine/Retigabine 300 mg	0 of 5 (0%)	1 of 5 (20%)	Not reported
Regimen A: Ezogabine/Retigabine 300 mg, Then 450 mg	0 of 5 (0%)	1 of 5 (20%)	Not reported
Regimen A: Ezogabine/Retigabine 300/450 mg, Then 600 mg	0 of 4 (0%)	1 of 4 (25%)	Not reported
Regimen A: Ezogabine/Retigabine 300/450/600 mg, Then 750 mg	0 of 4 (0%)	0 of 4 (0%)	Not reported
Regimen A: Ezogabine/Retigabine 300/450/600/750, Then 900 mg	0 of 3 (0%)	0 of 3 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 27877093Tompson DJ, Buraglio M, Andrews SM, Wheless JW. Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for Partial-Onset Seizures: Pharmacokinetics and Tolerability. J Pediatr Pharmacol Ther. 2016 Sep-Oct;21(5):404-412. doi: 10.5863/1551-6776-21.5.404.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ezogabine/retigabine in people with Epilepsy, run by GlaxoSmithKline at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) Following Oral Administration of Ezogabine/Retigabine (time frame: Pre-dose and 0.5, 1, 1.5, 2, 4, 6, and 8 hours post-dose on Day 7, Day 21, and Day 35). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01494584, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2020.