Clinical trial NCT01227902: Study of Retigabine Immediate Release as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults With Partial-Onset Seizures
Official title: An Open-Label, Flexible-Dose Study of Retigabine Immediate Release (IR) as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults With Partial -Onset Seizures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Seizures
retigabine IR
GW582892
Epilepsy
Open label, flexible dose
Partial-onset seizures
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-10-25
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this Phase III study is to evaluate the efficacy, safety and tolerability and health outcomes of retigabine Immediate Release (IR) as adjunctive therapy to each of the following monotherapy Antiepileptic Drug (AED) treatments: carbamazepine/oxcarbazepine, lamotrigine, levetiracetam, or valproic acid in adult subjects with partial-onset seizures (POS) using a flexible dosing regimen.

Detailed description: This is an open-label, multi-centre, flexible dose study of retigabine immediate release (IR). The study will enroll male and female outpatients (≥ 18 years of age) with partial-onset seizures (POS) who are inadequately controlled on their current monotherapy Antiepileptic Drug (AED). Following a Screening Period of up to 2 weeks, subjects will enter an 8-week Baseline Phase to determine baseline seizure frequency. At the end of the Baseline Phase, subjects who meet or exceed the minimum seizure frequency of 4 partial seizures per 56 days, will enter the Treatment Period (4 weeks Titration, 16 weeks Flexible Dose Evaluation Phase). All subjects will receive retigabine IR starting at 150 mg/day and will be titrated to 600 mg/day by Week 4. From Week 5 onwards, subjects' doses will be maintained between 300 to 1200 mg/day using a flexible dosing regimen to optimise response and tolerability. The maximum duration of the study is approximately 33 weeks (inclusive of a 3 week Taper/Follow-up Phase).

Eligibility criteria: Inclusion Criteria:

* Is 18 years of age (men or women)
* Has a confident diagnosis of epilepsy with partial-onset seizures i.e., simple or complex partial seizures with or without secondary generalization (International League Against Epilepsy (ILAE) classification; 1981) for more than 24 weeks prior to the start of Baseline phase.
* Has experienced at least 4 partial-onset seizures (i.e., simple or complex partial seizures with or without secondary generalization) during an 8-week (i.e., 56 days) prospective Baseline Phase with at least one partial seizure occurring during each 4 week (i.e., 28-day) period.
* Receiving a stable dose of one of the following AEDs: carbamazepine/oxcarbazepine, lamotrigine, levetiracetam or valproic acid. The AED dose must be stable 4 weeks prior to start of collection of baseline seizure data (retrospective or prospective) and during the Baseline period.
* Is able and willing to maintain an accurate and complete daily written seizure calendar and functional status diary or has a caregiver who is able and willing to do so for the entire duration of the study.
* Is able to comply with dosing of study drug, background AED and all study procedures.
* Has given written informed consent, or has a legally authorized representative who has given written informed consent, prior to the performance of any study assessments.
* A female subject is eligible to enter and participate in the study if she is either of non-childbearing potential or child-bearing potential but has a negative pregnancy test at Screening and agrees to satisfy one of the contraception methods as listed in the protocol, and is not pregnant or lactating or planning to become pregnant during the study.
* French subjects only: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

* Has a history of generalised epilepsy (e.g. Lennox-Gastaut, Juvenile Myoclonic etc.)
* Has had status epilepticus (other than simple partial status epilepticus) within the 24 weeks prior to Baseline Visit.
* Has participated in a previous retigabine study (subjects with documented evidence of having received placebo will be eligible).
* Is currently or has been abusing substance(s) or other medications in the 12 months prior to Baseline visit.
* Has taken an investigational drug, or used an investigational device, within the previous 30 days prior to screening or plans to take an investigational drug anytime during the study.
* Is currently following or planning to follow the ketogenic diet.
* Has been treated with vigabatrin within the past 6 months prior to collection of baseline seizure data.
* Is planning surgery or implantation of a Vagus Nerve Stimulator (VNS) to control seizures during the study.
* Is 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.
* Has any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome.
* Has a QTc ≥450 millisecond (msec) or greater than or equal to 480 msec for subjects with Bundle Branch Block at the time of screening.
* Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months. Has history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt.
* French Subjects: the French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).

Primary outcomes:
measure: Number of Participants With a >=50% Reduction in Partial-onset Seizure (POS) Frequency From Baseline
timeFrame: From Baseline through Week 20 (Day 140)/Early Withdrawal
Secondary outcomes:
measure: Number of Participants With the Indicated Reduction or Increase From Baseline in Partial-onset Seizure Frequency
timeFrame: From Baseline through Week 20 (Day 140)/Early Withdrawal
measure: Number of Participants With a >=25%, >=75%, or 100% Reduction in Partial-onset Seizure Frequency From Baseline
timeFrame: From Baseline through Week 20 (Day 140)/Early Withdrawal
measure: Percent Change From Baseline in Partial-onset Seizure Frequency
timeFrame: From Baseline through Week 20 (Day 140)/Early Withdrawal
measure: Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Worry
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Limitation of Ability to do What You Needed to
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Limitation of Ability to do What You Wanted to
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Percent Change From Baseline in Functional Status: Percentage of Days With no Missed Work or School Time
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Change From Baseline in the Short Form 36 Health Survey, Version 2 (SF-36v2) Domain Scores at Week 20/Early Withdrawal
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Change From Baseline in the SF-36v2 Physical Component Summary Score at Week 20/Early Withdrawal
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Change From Baseline in the SF-36v2 Mental Component Summary Score at Week 20/Early Withdrawal
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Number of Participants With the Indicated Response for the Epilepsy-related Worry Component of the Patient Global Impression of Change (PGI-C) Score
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Change From Baseline in the PGI-C Score: Epilepsy-related Worry
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Number of Participants With the Indicated Response for the Current Ability to do the Things You Need to do Component of the PGI-C Score
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Change From Baseline in the PGI-C Score: Current Ability to do the Things You Need to do
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Number of Participants With the Indicated Response for the Current Ability to do the Things You Want to do Component of the PGI-C Score
timeFrame: Baseline through Week 20/Early Withdrawal
measure: Change From Baseline in the PGI-C Score: Current Ability to do the Things You Want to do
timeFrame: Baseline through Week 20/Early Withdrawal
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Pleven
country: Bulgaria
facility: GSK Investigational Site
city: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Dianalund
country: Denmark
facility: GSK Investigational Site
city: Glostrup
country: Denmark
facility: GSK Investigational Site
city: Koebenhavn Oe
country: Denmark
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Limoges
country: France
facility: GSK Investigational Site
city: Lyon
country: France
facility: GSK Investigational Site
city: Nancy cedex
country: France
facility: GSK Investigational Site
city: Rennes Cedex
country: France
facility: GSK Investigational Site
city: Strasbourg Cedex
country: France
facility: GSK Investigational Site
city: Kehl-Kork
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Marburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Bielefeld
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Reggio Calabria
country: Italy
facility: GSK Investigational Site
state: Calabria
city: Bologna
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Torrette di Ancona
country: Italy
facility: GSK Investigational Site
state: Marche
city: Foggia
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Palermo
country: Italy
facility: GSK Investigational Site
state: Sicilia
city: Pisa
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Siena
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Den Haag
country: Netherlands
facility: GSK Investigational Site
city: Heemstede
country: Netherlands
facility: GSK Investigational Site
city: Heeze
country: Netherlands
facility: GSK Investigational Site
city: Ilawa
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Belgorod
country: Russian Federation
facility: GSK Investigational Site
city: Kazan
country: Russian Federation
facility: GSK Investigational Site
city: Krasnodar
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: Smolensk
country: Russian Federation
facility: GSK Investigational Site
city: St.-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vigo
country: Spain
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Songkla
country: Thailand
facility: GSK Investigational Site
city: Dnepropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Donetsk
country: Ukraine
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Lugansk
country: Ukraine
facility: GSK Investigational Site
city: Lviv
country: Ukraine
facility: GSK Investigational Site
city: Odesa
country: Ukraine
facility: GSK Investigational Site
city: Oleksandrivka village, Odesa
country: Ukraine
facility: GSK Investigational Site
city: Poltava
country: Ukraine
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: