EpilepsyPhase 3NCT01648101

Assessment of the Efficacy and Safety of 2 Doses of Retigabine Immediate Release (900 mg/Day and 600 mg/Day) Used as Adjunctive Therapy in Adult Asian Subjects With Drug-resistant Partial-onset Seizures

A Phase 3 study testing Retigabine 900mg/day and Retigabine 600mg/day in people with Epilepsy, run by GlaxoSmithKline at 41 sites in 7 countries.

Terminated

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

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Epilepsy
What is being tested?: Retigabine 900mg/day and Retigabine 600mg/day
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 76 participants
Where: 41 sitesin 7 countries
Study dates: 29 Aug 2012to 23 Dec 2013
Phase: Phase 3
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects eligible for enrolment in the study must meet all of the following criteria:
Asian men or women ≥18 years of age at the time of consent.
Have a confident diagnosis of epilepsy with POS with or without secondary generalisation (classified according to International League Against Epilepsy, 1981) for ≥2 years and is having POS despite having been treated in the past with ≥2 approved AEDs either alone or together at adequate doses for a sufficient length of time in the opinion of the investigator.
Have had, within the last 10 years, 1 electroencephalogram or video electroencephalogram and 1 brain magnetic resonance imaging or computerised tomography scan with results consistent with a diagnosis of POS. If diagnostic studies are negative and if history during clinical assessment suggests a diagnosis of POS, and other diseases have been excluded, the subject can be enrolled.
Have a documented 28-day partial seizure frequency rate of ≥4 partial seizures over the 8 weeks preceding the screening visit. subjects should not be seizure free for ≥21 consecutive days. In subjects with simple partial seizures, only seizures with motor signs will be counted towards meeting the inclusion criteria.
Currently being treated with a stable regimen of 1, 2, or 3 AEDs for ≥1 month prior to the screening visit. If the subject is taking barbiturates (e.g., phenobarbital), the dose of the barbiturate must have been stable for ≥3 months prior to the screening visit Note: Vagus Nerve Stimulator: VNS will not be counted as a concurrent AED. Subjects with surgically implanted VNS will be allowed to enter the study provided that all of the following conditions are met: a. The VNS has been in place for ≥6 months prior to the screening visit; b. The settings must have remained constant for ≥1 month prior to the screening visit and remain constant throughout the study; c. The battery is expected to last for the duration of the study; d. Subjects who are considering implantation of a VNS are excluded from participation in the study. Note: Benzodiazepines: The chronic use of a benzodiazepine as a concurrent AED is permitted as long as the dose is kept constant for ≥1 month prior to the screening visit and remains constant throughout the study.

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Able and willing to maintain an accurate and complete daily written seizure calendar or has a caregiver who is able and willing to maintain an accurate and complete daily written seizure calendar.
Able to understand and willing to provide written informed consent, or has a legally authorised representative able to so, before any protocol-specific procedures are performed.
A female subject is eligible to enter and participate in the study if she is: a. Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is postmenopausal); Premenopausal females with a documented (medical report verification) hysterectomy with or without oophorectomy or bilateral oophorectomy when reproductive status has been confirmed by hormone level assessment; Postmenopausal females defined as being amenorrheic for greater than 1 year with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms). However, if indicated, this should be confirmed by estradiol and follicle-stimulating hormone levels consistent with menopause (according to local laboratory ranges). Women who have not been confirmed as postmenopausal should be advised to use contraception as listed in the protocol: b. Of childbearing potential, has a negative serum pregnancy test at Screening and a negative urine and serum pregnancy test at randomisation, and agrees to satisfy one of the requirements listed in the protocol: c. Not pregnant or lactating (breastfeeding) or planning to become pregnant during the study.
Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2 times the upper limit of normal (ULN); alkaline phosphatase (ALP) and bilirubin </=1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%).

Who cannot join

Subjects meeting any of the following criteria must not be enrolled in the study:
Have generalised epilepsy (such as Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, absence epilepsy, etc.), innumerable seizures within the 12-month period prior to study entry where the individual seizures cannot be counted, or nonepileptic seizures.
Have had status epilepticus (other than simple partial status epilepticus) within the 12 months prior to Screening.
Have had previous exposure to retigabine.
Have impaired renal function as judged by a creatinine clearance of <50 mL/min.
Have a history of substance abuse (alcohol or drugs) or substance dependence within 12 months prior to Screening.

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Have taken an investigational drug, or used an investigational device, within the 30 days prior to Screening or plans to take another investigational drug at any time during the study.
Are currently following or planning to follow a ketogenic diet.
Have been treated with felbamate or vigabatrin within the 6 months prior to Screening. If a subject has been previously treated with vigabatrin >6 months prior to Screening, a visual perimetry test performed within 6 months prior to Screening must show normal visual fields or no worsening of recognised visual field abnormalities as compared with prior to vigabatrin treatment.
Are using central nervous system (CNS)-active medication (other than concomitant AED therapy), unless the subject has been stabilised on such medication for more than 1 month prior to Screening; or currently taking medications known to lower seizure threshold (e.g., antipsychotics) and monoamine oxidase (MAO) inhibitors.
Are using herbal treatments with CNS activity within 1 month prior to Screening.
Are planning surgery during the study to control seizures.
Are suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that are likely to interfere with the objectives of the study.
Have a history of urinary retention or risk factors for urinary retention that in the investigator's judgment could potentially affect subject safety.
Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, or hepatic conditions; or a condition that affects the absorption, distribution, metabolism or excretion of drugs.
Have an average corrected QT interval (QTc; either QTcB Bazett's correction or QTcF Fridericia's correction) ≥450 msec or ≥480 msec for subjects with bundle branch block at the time of Screening.
Have active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Have a history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
Have a history of malignancy within the past 2 years, with the exception of basal cell carcinoma.
Have a known hypersensitivity to any components of the study medication.
Randomisation Criteria:
Subjects must also meet the following criteria at the end of the Baseline Phase (Visit 3) and before randomisation and administration of the first dose of study medication:
Have a documented 28-day total POS frequency rate of ≥4 POS over an 8 week Baseline Phase. Note: In subjects with simple partial seizures, although all seizures occurring during the Baseline Phase will be collected, only seizures with motor signs will be counted toward qualification for meeting the randomisation criteria.
Have not had a seizure-free period of ≥21 consecutive days during the Baseline Phase.
Have not had innumerable seizures (defined as an episode of seizure activity lasting <30 minutes during which several seizures occur with such frequency that the initiation and termination of each individual seizure cannot be distinguished) during the 8 week Baseline Phase.
Have not had an episode of status epilepticus (other than simple partial status epilepticus) during the 8 week Baseline Phase
Have not required dose adjustments of concurrent AEDs, addition of new AEDs, discontinuation of existing AEDs, changes to VNS settings, or acute use of benzodiazepines for the treatment of seizures during the Baseline Phase.

Trial locations and contacts

41 sites in 7 countries.

Country

City, postcode or hospital

41 sites in 7 countries

South Korea17 sites

GSK Investigational Site
Busan, 602-715
GSK Investigational Site
Busan, 612-865
GSK Investigational Site
Daegu, 700-712
GSK Investigational Site
Daegu, 705-718
GSK Investigational Site
Daejeon, 301-721
GSK Investigational Site
Gyeonggi-do, 442-723
GSK Investigational Site
Gyeonggi-do, 463-707
GSK Investigational Site
Incheon, 405-760
GSK Investigational Site
Seoul, 110-744
GSK Investigational Site
Seoul, 120-752
GSK Investigational Site
Seoul, 135-710
GSK Investigational Site
Seoul, 135-720
GSK Investigational Site
Seoul, 136-705
GSK Investigational Site
Seoul, 137-701
GSK Investigational Site
Seoul, 138-736
GSK Investigational Site
Seoul, 143-729
GSK Investigational Site
Seoul, 150-713

Other trials in South Korea

Taiwan10 sites

GSK Investigational Site
Changhua, 50006
GSK Investigational Site
Kaohsiumg, 386
GSK Investigational Site
Kaohsiung City, 83301
GSK Investigational Site
New Taipei City, 10016
GSK Investigational Site
Taichung, 40705
GSK Investigational Site
Tainan, 70403
GSK Investigational Site
Tainan, 71004
GSK Investigational Site
Taipei, 11031
GSK Investigational Site
Taipei, 110
GSK Investigational Site
Tau-Yuan, 333

Other trials in Taiwan

Hong Kong4 sites

GSK Investigational Site
Hang Hau
GSK Investigational Site
Hong Kong
GSK Investigational Site
Kowloon
GSK Investigational Site
Shatin

Other trials in Hong Kong

Thailand4 sites

GSK Investigational Site
Bangkok, 10330
GSK Investigational Site
Bangkok, 10400
GSK Investigational Site
Chiang Mai, 50200
GSK Investigational Site
Khon Kaen, 40002

Other trials in Thailand

Philippines3 sites

GSK Investigational Site
Cebu City, 6000
GSK Investigational Site
Davao City, 8000
GSK Investigational Site
Manila, 1003

Other trials in Philippines

Malaysia2 sites

GSK Investigational Site
Kuala Lumpur, 59100
GSK Investigational Site
Seberang Jaya, 13700

Other trials in Malaysia

Singapore1 site

GSK Investigational Site
Singapore, 119074

Other trials in Singapore

About this study

Official title: A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multicentre Study to Determine the Efficacy and Safety of 2 Doses of Retigabine Immediate Release (900 mg/Day and 600 mg/Day) Used as Adjunctive Therapy in Adult Asian Subjects With Drug-resistant Partial-onset Seizures.

The immediate release (IR) formulation of retigabine has been shown to be superior to placebo as adjunctive therapy in 3 adequate and well-controlled studies in subjects with drug-resistant partial-onset seizures (POS) who had previously failed to respond to two or more antiepileptic drugs (AEDs) and were still having seizures despite current treatment with 1, 2, or 3 AEDs. However, of 1244 subjects randomly assigned to treatment in these 3 clinical studies, only 10 were Asian subjects and only 5 of these Asian subjects were randomly assigned to treatment with retigabine. Therefore, this Phase III study is being conducted to evaluate the efficacy, safety and tolerability, and health outcomes of retigabine, at doses of 900 mg/day and 600 mg/day, compared with placebo in adult Asian subjects with drug-resistant POS.

Read the detailed description

This is a Phase III study evaluating the efficacy, safety and tolerability, and health outcomes of 2 doses of retigabine immediate release (IR) (GW582892) compared with placebo in adult Asian subjects with drug-resistant partial-onset seizures (POS) who are already taking 1, 2, or 3 antiepileptic drugs (AEDs). This randomised, double-blind, placebo-controlled, parallel-group study will compare retigabine IR at doses of 900 mg/day and 600 mg/day taken in equally divided doses three times a day with placebo.

The study design includes an 8-week Screening/Baseline Phase, a 16-week Treatment Phase (4-week Titration Phase and 12-week Maintenance Phase), and a 4-week Transition or Taper/Follow-up Phase. Approximately 500 subjects will be screened and enrolled with approximately 354 subjects randomly assigned to 1 of 3 treatment groups in a ratio of 1:1:1 (retigabine 900 mg/day, retigabine 600 mg/day, or placebo). The total duration of the study for each subject will be approximately 28 weeks. At the end of the Maintenance Phase, eligible subjects will be given the opportunity to enrol in an open-label extension study.

The primary efficacy endpoint is the proportion of responders, defined as subjects with >/=50% reduction in 28 day total POS frequency, from the Baseline Phase to the Maintenance Phase, in subjects randomly assigned to retigabine 900 mg/day compared with placebo. The key secondary efficacy endpoint is the proportion of responders, defined as subjects with >/=50% reduction in 28 day total POS frequency, from the Baseline Phase to the Maintenance Phase, in subjects randomly assigned to retigabine 600 mg/day compared with placebo.

The safety and tolerability endpoints are incidence and severity of adverse events (AEs); proportion of subjects with AEs leading to discontinuation; change from Baseline in vital sign measurements and weight; change from Baseline in electrocardiogram parameters; change from Baseline in haematology, chemistry, and urinalysis parameters; changes from Baseline in American Urological Association Symptom Index and post-void residual bladder ultrasound volumes; and summary of the Columbia-Suicide Severity Rating Scale.

Conditions: Epilepsy
Being tested: Retigabine 900mg/day, Retigabine 600mg/day, Placebo
Keywords: Retigabine IR, Asian Subjects, Adjunctive Therapy, Efficacy, Drug-Resistant, Safety & tolerability, Partial-Onset Seizures, Epilepsy
Medical subject headings: Epilepsy

What participants receive

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

Retigabine 900mg/dayDrug
Study drug will be administered three times a day in a double blind manner. The starting dose of retigabine will be 300 mg/day. This dose will be increased by 150 mg/day per week to reach the target dose of 900mg/day over a 4 week Titration Phase). The subject will then continue to receive 900mg/day for the next 12 weeks (Maintenance Phase). Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. After a 4 week transition phase, eligible subjects will start the OLE on retigabine 900mg/day.
Retigabine 600mg/dayDrug
Study drug will be administered three times a day in a double blind manner. The starting dose of retigabine will be 300mg/day. This dose will be increased by 150 mg/day per week to reach the target dose of 600mg/day over 2 weeks. The subject will then continue to receive 600mg/day for the next 14 weeks (2 weeks of the Titration Phase and 12 weeks of the Maintenance Phase). Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. After a 4 week Transition Phase (3 weeks on retigabine 600mg/day, 1 week on retigabine 750mg/day) eligible subjects will start the OLE on retigabine 900mg/day.
PlaceboOther
Study drug will be administered three times a day in a double blind manner. Subjects randomised to placebo will receive the same number, size and colour of tablets as the 600mg/day and 900mg/day treatment arms for the duration of the 4 week Titration Phase and the 12 week Maintenance Phase. Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. The starting dose of retigabine will be 300 mg/day. This dose will be increased by 150 mg/day per week to reach dose of 750mg/day over the 4 weeks of the Transition Phase. On completion of the Transition Phase eligible subjects will start the OLE on retigabine 900mg/day.

Study groups in NCT01648101
Study group	Role	What they receive
Retigabine 900mg	Experimental	900mg total daily dose Receives: Drug: Retigabine 900mg/day
Retigabine 600mg	Experimental	600mg total daily dose Receives: Drug: Retigabine 600mg/day
Placebo	Placebo comparator	Placebo Receives: Other: Placebo

What is being measured

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

Number of Placebo and Retigabine 900 mg Responders During the Maintenance Phase (MP)
A responder is defined as a par. with >=50% reduction in the 28 day total partial on-set seizure (POS) frequency from the Baseline Phase (BP) to the MP, randomly assigned to retigabine 900 mg/day compared with placebo. The total 28-day POS rate was defined as: (total number of POS over the evaluable period (MP) / number of days of seizure (sz) data in the evaluable period) *28 days. In the event of one or more innumerable seizures (IS) occurring on a day, these were to be counted as an additional 10 seizures for that day, regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of MP minus start date of the MP minus days on which seizures were recorded as "Not done" + 1). Each occurrence of status epilepticus (SE) was counted as 1 seizure (whether partial or not).
Measured: Baseline (BL); Week 4 up to Week 16

Secondary outcomes (13)

Number of Placebo and Retigabine 600 mg Responders During the MP
A "responder" is defined as a participant experiencing a >=50% reduction in the 28-day total POS frequency from the BP to the MP, randomly assigned to retigabine 600 mg/day compared to placebo. The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [MP] / number of applicable days in that period) * 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1). Each occurrence of SE was counted as 1 seizure (whether partial status or not).
Measured: Baseline; Week 4 up to Week 16
Number of Responders From the BP to the Treatment Phase (TrP)
A "responder" is defined as a participant experiencing a >=50% reduction in the 28-day total POS frequency from the BP to the TrP (TiP plus MP). The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [TrP] / number of applicable days in that period) * 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1). Each occurrence of SE was counted as 1 seizure (whether partial status or not).
Measured: From Baseline up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the MP
The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [MP] / number of applicable days in that period) * 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1. Percent change from Baseline was calculated as: ([the 28-day PS rate for the period of interest (MP) minus the Baseline 28-day PS rate] / Baseline 28-day PS rate) * 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.
Measured: Baseline; Week 4 up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the TrP
The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [TrP; TiP plus MP] / number of applicable days in that period) * 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1. Percent change from Baseline was calculated as: ([the 28-day PS rate for the period of interest (TrP) minus the Baseline 28-day PS rate] / Baseline 28-day PS rate) * 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.
Measured: From Baseline up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the MP Categorized as: no Change/Increase, >0% to <50% Decrease, 50% to 75% Decrease, and >75% to 100% Decrease
The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [MP] / number of applicable days in that period) * 28. In a case of >=1 occurrence of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1. Percent change from Baseline was calculated as: ([the 28-day PS rate for the period of interest (MP) minus the Baseline 28-day PS rate] / Baseline 28-day PS rate) * 100. A negative percent change indicates a reduction (improvement) from Baseline. There was no theoretical upper limit for worsening. Each occurrence of status epilepticus (SE) was counted as 1 seizure (whether partial status or not).
Measured: Baseline; Week 4 up to Week 16
Percent Change From Baseline in 28 Day Total POS Frequency During the TrP Categorized as: no Change/Increase, >0% to <50% Decrease, 50% to 75% Decrease, and >75% to 100% Decrease
The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [TrP; TiP plus MP] / number of applicable days in that period) * 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1. Percent change from Baseline was calculated as: ([the 28-day PS rate for the period of interest (TrP) minus the Baseline 28-day PS rate] / Baseline 28-day PS rate) * 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.
Measured: From Baseline up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the MP Categorized as: >25% Increase and 0% to 25% Increase
The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [MP] / number of applicable days in that period) * 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the MP minus the start date of the MP minus days on which seizures were recorded as "Not Done" during the MP plus 1. Percent change from Baseline was calculated as: ([the 28-day PS rate for the period of interest (MP) minus the Baseline 28-day PS rate] / Baseline 28-day PS rate) * 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.
Measured: Baseline; Week 4 up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the TrP Categorized as: >25% Increase and 0% to 25% Increase
The 28-day total POS frequency was calculated as: (total number of PS over the time period of interest [TrP; TiP plus MP] / number of applicable days in that period) * 28. In a case of one or more occurrences of IS on a day, these seizures were to be counted as an additional 10 seizures for that day, regardless of whether the IS were PS or not, and regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of the TrP minus the start date of the TrP minus days on which seizures were recorded as "Not Done" during the TrP plus 1. Percent change from Baseline was calculated as: ([the 28-day PS rate for the period of interest (TrP) minus the Baseline 28-day PS rate] / Baseline 28-day PS rate) * 100. A negative percent change indicates a reduction (improvement) from Baseline; thus, the best possible outcome is -100% (100% reduction). There was no theoretical upper limit for worsening.
Measured: From Baseline up to Week 16
Number of Participants Who Were Seizure Free During the MP, ITT Population
A seizure free-day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the MP if he/she had no record of countable seizures of any type, no IS, and no SE during the MP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day. Participants who did not complete the study or experienced any seizures in the MP were not considered to be seizure free. A participant who completed the study AND had no seizures during the maintenance phase were counted to be seizure free. Also, a completer who only had seizures during the TiP is considered seizure free.
Measured: Baseline; Week 4 up to Week 16
Number of Participants Who Were Seizure Free During the TrP
A seizure free-day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the TrP if he/she had no record of countable seizures of any type, no IS, and no SE during the TrP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day. A participant was considered to be seizure free if they experienced no seizures in the TiP or MP regardless of how long they were in the study.
Measured: From Baseline up to Week 16
Percentage of Seizure-free Days in the MP
The percentage of seizure-free days was calculated as: (total number of days without seizures in the MP / number of applicable days in the MP) * 100. A seizure-free day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the MP if he/she had no record of countable seizures of any type, no IS, and no SE during the MP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day.
Measured: From Week 4 up to Week 16
Percentage of Seizure-free Days in the TrP
The percentage of seizure-free days was calculated as: (total number of days without seizures in the TrP (TiP plus MP) / number of applicable days in the TrP) * 100. A seizure-free day is defined as a day with non-missing seizure data but without any seizures. A participant was considered to be seizure free during the TrP if he/she had no record of countable seizures of any type, no IS, and no SE during the TrP. Participants who had one or more days on which they recorded seizures as "Not Done" on the seizure calendar were not disqualified from being considered as seizure free for that day.
Measured: From Baseline up to Week 16
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline
A participant was considered to have new seizure types during the TrP if they experienced a new seizure types (such as SE, myoclonic, absence, secondary generalization) and had no prior history of these seizure types. At Screening, a history of previous seizure types was collected, with "Yes," "No," "IS," "SE," or "Unknown" being recorded for each of the seizures types. The history of seizure types was updated during the 8-week BP as pre-treatment status. New types of seizures during the TrP were recorded as A1=simple PS with motor signs; AX=simple PS without motor signs; B=complex PS; C=PS evolving to secondary generalized seizures; D1=absence of seizures; D2=myoclonic seizures; D3=clonic seizures; D4=tonic seizures; D5=tonic-clonic seizures; D6=atonic seizures; E=unclassified seizures; and SE=status epilepticus.
Measured: From Baseline up to Week 16

Timeline

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

29 Aug 201223 Dec 2013

First posted24 Jul 2012 (estimated)
Study start29 Aug 2012
Primary completion1 Dec 2013
Study completion23 Dec 2013

Why it stopped: Registration of the medicine is no longer being pursued in South Korea, Taiwan or Vietnam

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 76 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01648101
Sponsor's protocol ID: 114855
Status last verified: Jun 2018
First submitted: 28 Jun 2012
Last updated: 13 Aug 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981 Aug;22(4):489-501. doi: 10.1111/j.1528-1157.1981.tb06159.x. No abstract available.
PubMed 6790275

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All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multicentre Study to Determine the Efficacy and Safety of 2 Doses of Retigabine Immediate Release (900 mg/Day and 600 mg/Day) Used as Adjunctive Therapy in Adult Asian Subjects With Drug-resistant Partial-onset Seizures.
ClinicalTrials.gov ID: NCT01648101
Acronym / sponsor ID: 114855
Conditions: Epilepsy
Keywords: Retigabine IR, Asian Subjects, Adjunctive Therapy, Efficacy, Drug-Resistant, Safety & tolerability, Partial-Onset Seizures, Epilepsy
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Registration of the medicine is no longer being pursued in South Korea, Taiwan or Vietnam
Enrolment: 76 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 29 Aug 2012
Primary completion: 1 Dec 2013 (actual)
Study completion: 23 Dec 2013 (actual)
First posted: 24 Jul 2012 (estimated)
Results: Posted 8 Sep 2014

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Retigabine 900mg	Experimental	Drug: Retigabine 900mg/day900mg total daily dose
Retigabine 600mg	Experimental	Drug: Retigabine 600mg/day600mg total daily dose
Placebo	Placebo comparator	Other: PlaceboPlacebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Asian men or women ≥18 years of age at the time of consent.
Have a confident diagnosis of epilepsy with POS with or without secondary generalisation (classified according to International League Against Epilepsy, 1981) for ≥2 years and is having POS despite having been treated in the past with ≥2 approved AEDs either alone or together at adequate doses for a sufficient length of time in the opinion of the investigator.
Have had, within the last 10 years, 1 electroencephalogram or video electroencephalogram and 1 brain magnetic resonance imaging or computerised tomography scan with results consistent with a diagnosis of POS. If diagnostic studies are negative and if history during clinical assessment suggests a diagnosis of POS, and other diseases have been excluded, the subject can be enrolled.
Have a documented 28-day partial seizure frequency rate of ≥4 partial seizures over the 8 weeks preceding the screening visit. subjects should not be seizure free for ≥21 consecutive days. In subjects with simple partial seizures, only seizures with motor signs will be counted towards meeting the inclusion criteria.
Currently being treated with a stable regimen of 1, 2, or 3 AEDs for ≥1 month prior to the screening visit. If the subject is taking barbiturates (e.g., phenobarbital), the dose of the barbiturate must have been stable for ≥3 months prior to the screening visit Note: Vagus Nerve Stimulator: VNS will not be counted as a concurrent AED. Subjects with surgically implanted VNS will be allowed to enter the study provided that all of the following conditions are met: a. The VNS has been in place for ≥6 months prior to the screening visit; b. The settings must have remained constant for ≥1 month prior to the screening visit and remain constant throughout the study; c. The battery is expected to last for the duration of the study; d. Subjects who are considering implantation of a VNS are excluded from participation in the study. Note: Benzodiazepines: The chronic use of a benzodiazepine as a concurrent AED is permitted as long as the dose is kept constant for ≥1 month prior to the screening visit and remains constant throughout the study.

Key exclusion criteria (26 listed)

Have generalised epilepsy (such as Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, absence epilepsy, etc.), innumerable seizures within the 12-month period prior to study entry where the individual seizures cannot be counted, or nonepileptic seizures.
Have had status epilepticus (other than simple partial status epilepticus) within the 12 months prior to Screening.
Have had previous exposure to retigabine.
Have impaired renal function as judged by a creatinine clearance of <50 mL/min.
Have a history of substance abuse (alcohol or drugs) or substance dependence within 12 months prior to Screening.

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
Retigabine 900mg/dayStudy drug will be administered three times a day in a double blind manner. The starting dose of retigabine will be 300 mg/day. This dose will be increased by 150 mg/day per week to reach the target dose of 900mg/day over a 4 week Titration Phase). The subject will then continue to receive 900mg/day for the next 12 weeks (Maintenance Phase). Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. After a 4 week transition phase, eligible subjects will start the OLE on retigabine 900mg/day.	Drug	Retigabine 900mg
Retigabine 600mg/dayStudy drug will be administered three times a day in a double blind manner. The starting dose of retigabine will be 300mg/day. This dose will be increased by 150 mg/day per week to reach the target dose of 600mg/day over 2 weeks. The subject will then continue to receive 600mg/day for the next 14 weeks (2 weeks of the Titration Phase and 12 weeks of the Maintenance Phase). Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. After a 4 week Transition Phase (3 weeks on retigabine 600mg/day, 1 week on retigabine 750mg/day) eligible subjects will start the OLE on retigabine 900mg/day.	Drug	Retigabine 600mg
PlaceboStudy drug will be administered three times a day in a double blind manner. Subjects randomised to placebo will receive the same number, size and colour of tablets as the 600mg/day and 900mg/day treatment arms for the duration of the 4 week Titration Phase and the 12 week Maintenance Phase. Eligible subjects will then be offered an opportunity to enter an open label extension (OLE) study. The starting dose of retigabine will be 300 mg/day. This dose will be increased by 150 mg/day per week to reach dose of 750mg/day over the 4 weeks of the Transition Phase. On completion of the Transition Phase eligible subjects will start the OLE on retigabine 900mg/day.	Other	Placebo

Primary outcome

Number of Placebo and Retigabine 900 mg Responders During the Maintenance Phase (MP)
Time frame: Baseline (BL); Week 4 up to Week 16
A responder is defined as a par. with >=50% reduction in the 28 day total partial on-set seizure (POS) frequency from the Baseline Phase (BP) to the MP, randomly assigned to retigabine 900 mg/day compared with placebo. The total 28-day POS rate was defined as: (total number of POS over the evaluable period (MP) / number of days of seizure (sz) data in the evaluable period) *28 days. In the event of one or more innumerable seizures (IS) occurring on a day, these were to be counted as an additional 10 seizures for that day, regardless of the number of occurrences of IS on that day. The number of applicable days in a phase for seizure data is calculated as: the end date of MP minus start date of the MP minus days on which seizures were recorded as "Not done" + 1). Each occurrence of status epilepticus (SE) was counted as 1 seizure (whether partial or not).

13 secondary outcomes

Number of Placebo and Retigabine 600 mg Responders During the MP
Time frame: Baseline; Week 4 up to Week 16
Number of Responders From the BP to the Treatment Phase (TrP)
Time frame: From Baseline up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the MP
Time frame: Baseline; Week 4 up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the TrP
Time frame: From Baseline up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the MP Categorized as: no Change/Increase, >0% to <50% Decrease, 50% to 75% Decrease, and >75% to 100% Decrease
Time frame: Baseline; Week 4 up to Week 16
Percent Change From Baseline in 28 Day Total POS Frequency During the TrP Categorized as: no Change/Increase, >0% to <50% Decrease, 50% to 75% Decrease, and >75% to 100% Decrease
Time frame: From Baseline up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the MP Categorized as: >25% Increase and 0% to 25% Increase
Time frame: Baseline; Week 4 up to Week 16
Percent Change From Baseline in the 28-day Total POS Frequency During the TrP Categorized as: >25% Increase and 0% to 25% Increase
Time frame: From Baseline up to Week 16
Number of Participants Who Were Seizure Free During the MP, ITT Population
Time frame: Baseline; Week 4 up to Week 16
Number of Participants Who Were Seizure Free During the TrP
Time frame: From Baseline up to Week 16
Percentage of Seizure-free Days in the MP
Time frame: From Week 4 up to Week 16
Percentage of Seizure-free Days in the TrP
Time frame: From Baseline up to Week 16
Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline
Time frame: From Baseline up to Week 16

Results and safety

Results posted to the registry on 8 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
Placebo	25	23
Retigabine 600 mg/Day	26	23
Retigabine 900 mg/Day	24	18

Primary outcome: Number of Placebo and Retigabine 900 mg Responders During the Maintenance Phase (MP)

Time frame: Baseline (BL); Week 4 up to Week 16. Number. Unit: Participants

Measure	Placebo n = 25	Retigabine 600 mg/Day n = 0	Retigabine 900 mg/Day n = 24
Responders	0	–	4
Non-Responders	25	–	20

Population analysed: ITT Population: all par. who were randomly assigned to treatment; rec'd≥1 dose (or any portion of dose) of study medication; had BL sz data; and had ≥1 post-BL sz record (whether or not they had a sz) between start of TiP and end of MP. Par. who dropped out during TiP were classified as non-responders. For all other par. only MP data were used.

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent SAEs and non-serious AEs were collected from start of study treatment until the end of the TnP for participants who entered the OLE study (up to Week 20), or until the follow-up visit for par. who entered the TaP (up to Week 20).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Retigabine 900 mg/Day	2 of 24 (8.3%)	20 of 24 (83.3%)	Not reported
Retigabine 600 mg/Day	1 of 26 (3.8%)	24 of 26 (92.3%)	Not reported
Placebo	1 of 25 (4%)	18 of 25 (72%)	Not reported

Limitations and caveats (from the sponsor): RTG114855 was designed for registration of retigabine as add-on treatment of drug-resistant POS in South Korea/Taiwan/ Vietnam. GSK decided not to pursue registration in these countries and terminated the study early based on new safety information.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 6790275Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1981 Aug;22(4):489-501. doi: 10.1111/j.1528-1157.1981.tb06159.x. No abstract available.
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Related trials for Epilepsy

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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

41 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Retigabine 900mg/day and Retigabine 600mg/day in people with Epilepsy, run by GlaxoSmithKline at 41 sites in 7 countries.

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 10 inclusion and 26 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 13 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in South Korea, Taiwan, Hong Kong, Thailand, Philippines and 2 more countries. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 8 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?

Number of Placebo and Retigabine 900 mg Responders During the Maintenance Phase (MP) (time frame: Baseline (BL); Week 4 up to Week 16). 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 NCT01648101, 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 13 Aug 2018.