Study of Retigabine Immediate Release as Adjunctive Therapy to Specified Monotherapy Antiepileptic Treatments in Adults With Partial-Onset Seizures

NCT01227902 | Completed Phase 3 Results

• 1 other identifier: 113905
• Study Type: interventional
• Target: 203
• Locations: 12 countries
• Sites: 66

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.

Conditions

Epilepsy

Keywords

Seizures; retigabine IR; GW582892; Epilepsy; Open label, flexible dose; Partial-onset seizures

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a >=50% Reduction in Partial-onset Seizure (POS) Frequency From Baseline

  The number of participants experiencing a \>=50% reduction from Baseline (BL) in POS frequency during the Treatment Phase (TP) (i.e., Titration Phase and Flexible Dose Evaluation \[FDE\] Phase) was measured. A POS has its onset in a limited area on one side of the brain. POSs may remain limited or may spread to involve both sides of the brain. For both the Baseline Phase and the TP, seizure frequency was calculated as a 28-day rate using the following formula: 28 x {\[(number of countable partial seizures in Phase) + (10 x number of days with innumerable seizures in Phase) + (number of occurrences of status epilepticus in Phase)\] / number of applicable days in the Phase}, where all days in the Phase are considered applicable (including days with 0 seizures), except for days on which the participant failed to complete the Seizure Diary. \>= 50% reduction from BL is calculated as 100 x (28-day partial seizure rate \[PSR\] for the TP - 28-day PSR for the BL Phase) / 28-day PSR for the BL Phase.

  From Baseline through Week 20 (Day 140)/Early Withdrawal

Secondary Outcomes (16)

• Number of Participants With the Indicated Reduction or Increase From Baseline in Partial-onset Seizure Frequency

  From Baseline through Week 20 (Day 140)/Early Withdrawal

• Number of Participants With a >=25%, >=75%, or 100% Reduction in Partial-onset Seizure Frequency From Baseline

  From Baseline through Week 20 (Day 140)/Early Withdrawal

• Percent Change From Baseline in Partial-onset Seizure Frequency

  From Baseline through Week 20 (Day 140)/Early Withdrawal

• Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Worry

  Baseline through Week 20/Early Withdrawal

• Functional Status Diary (FSD): Percent Change From Baseline in Epilepsy-related Limitation of Ability to do What You Needed to

  Baseline through Week 20/Early Withdrawal

Study Arms (1)

Retigabine IR

EXPERIMENTAL

Open Label flexible dose between 300 mg/day (minimum) and 1200 mg/day (maximum).

Drug: Retigabine IR

Interventions

Retigabine IR DRUG

Flexible dose between 300 mg/day (minimum) and 1200 mg/day (maximum).

Retigabine IR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (66)

GSK Investigational Site

Ghent, 9000, Belgium

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GSK Investigational Site

Leuven, 3000, Belgium

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GSK Investigational Site

Liège, 4000, Belgium

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GSK Investigational Site

Pleven, 5800, Bulgaria

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GSK Investigational Site

Plovdiv, 4000, Bulgaria

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GSK Investigational Site

Sofia, 1113, Bulgaria

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GSK Investigational Site

Sofia, 1431, Bulgaria

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GSK Investigational Site

Dianalund, 4293, Denmark

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GSK Investigational Site

Glostrup Municipality, 2600, Denmark

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GSK Investigational Site

Koebenhavn Oe, 2100, Denmark

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GSK Investigational Site

Lille, 59037, France

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GSK Investigational Site

Limoges, 87042, France

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GSK Investigational Site

Lyon, 69677, France

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GSK Investigational Site

Nancy, 54035, France

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GSK Investigational Site

Rennes, 35033, France

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GSK Investigational Site

Strasbourg, 67098, France

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GSK Investigational Site

Kehl-Kork, Baden-Wurttemberg, 77694, Germany

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GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70372, Germany

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GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

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GSK Investigational Site

Marburg, Hesse, 35043, Germany

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GSK Investigational Site

Bielefeld, North Rhine-Westphalia, 33617, Germany

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GSK Investigational Site

Bonn, North Rhine-Westphalia, 53105, Germany

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GSK Investigational Site

Kiel, Schleswig-Holstein, 24105, Germany

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GSK Investigational Site

Berlin, State of Berlin, 13509, Germany

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GSK Investigational Site

Foggia, Apulia, 71100, Italy

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GSK Investigational Site

Reggio Calabria, Calabria, 89100, Italy

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GSK Investigational Site

Bologna, Emilia-Romagna, 40139, Italy

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GSK Investigational Site

Rome, Lazio, 00163, Italy

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GSK Investigational Site

Rome, Lazio, 00185, Italy

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GSK Investigational Site

Genoa, Liguria, 16153, Italy

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GSK Investigational Site

Palermo, Sicily, 90129, Italy

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GSK Investigational Site

Torrette Di Ancona, The Marches, 60126, Italy

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GSK Investigational Site

Pisa, Tuscany, 56126, Italy

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GSK Investigational Site

Siena, Tuscany, 53100, Italy

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GSK Investigational Site

Breda, 4818 CK, Netherlands

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GSK Investigational Site

Heemstede, 2103 SW, Netherlands

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GSK Investigational Site

Heeze, 5591 VE, Netherlands

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GSK Investigational Site

The Hague, 2512 VA, Netherlands

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GSK Investigational Site

Iława, 13-300, Poland

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GSK Investigational Site

Katowice, 40-662, Poland

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GSK Investigational Site

Krakow, 31-209 Krakow, Poland

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GSK Investigational Site

Warsaw, 00-453, Poland

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GSK Investigational Site

Warsaw, 02-952, Poland

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GSK Investigational Site

Belgorod, 308007, Russia

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GSK Investigational Site

Kazan', 420064, Russia

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GSK Investigational Site

Krasnodar, 350007, Russia

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GSK Investigational Site

Moscow, 107150, Russia

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GSK Investigational Site

Moscow, 117049, Russia

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GSK Investigational Site

Saint Petersburg, 193019, Russia

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GSK Investigational Site

Samara, 443095, Russia

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GSK Investigational Site

Smolensk, 214 019, Russia

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Seville, 41009, Spain

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GSK Investigational Site

Valencia, 46026, Spain

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GSK Investigational Site

Vigo, 36204, Spain

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GSK Investigational Site

Bangkok, 10400, Thailand

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GSK Investigational Site

Khon Kaen, 40002, Thailand

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GSK Investigational Site

Songkhla, 90110, Thailand

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GSK Investigational Site

Dnipro, 49005, Ukraine

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GSK Investigational Site

Donetsk, 83037, Ukraine

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GSK Investigational Site

Kharkiv, 61068, Ukraine

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GSK Investigational Site

Luhansk, 91045, Ukraine

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GSK Investigational Site

Lviv, 79010, Ukraine

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GSK Investigational Site

Odesa, 65014, Ukraine

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GSK Investigational Site

Oleksandrivka Village, Odesa, 67513, Ukraine

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GSK Investigational Site

Poltava, Ukraine

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MeSH Terms

Conditions

Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2010
• First Posted: October 25, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: October 17, 2014
• Results First Posted: November 11, 2013

Record last verified: 2014-10

Locations

UA (8); BU (4); PL (5); DK (3); ES (4); TH (3); RU (8); FR (6); NL (4); DE (8); BE (3); IT (10)