Long-Term Safety Study of Retigabine Immediate Release (IR) as Adjunctive Therapy in the Treatment of Adults With Partial-Onset Seizures (POS).

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01336621
First received: March 10, 2011
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

The purpose of this Phase III study is to assess the long-term safety, tolerability and efficacy of flexibly dosed retigabine Immediate Release (IR) as adjunctive therapy in adult subjects with partial-onset seizures. In addition, those subjects who successfully completed 20 weeks of adjunctive treatment with retigabine IR in the parent study, RGB113905, and who were thought to have benefitted from treatment will be provided continued access to retigabine IR.


Condition Intervention Phase
Epilepsy
Drug: Retigabine IR
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicentre, Open-Label, Long-Term, Safety and Tolerability Study of Retigabine Immediate Release (IR) in Adults With Partial-Onset Seizures (Extension of Study RGB113905)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The proportion of subjects experiencing a ≥25%, ≥50%, ≥75% or 100% reduction in 28-day partial-onset seizure frequency from baseline during the treatment period. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: No ]
  • The percent change from baseline in 28-day partial-onset seizure frequency during the treatment period. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: No ]
  • The proportion of subjects experiencing an increase in 28-day partial-onset seizure frequency from baseline during the treatment period. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • The proportion of subjects who remain seizure free throughout the treatment period. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: No ]
  • Proportion of subjects withdrawing due to adverse events. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Change from baseline in vital signs (blood pressure and heart rate) and weight. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Change from baseline in ECG parameters. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Changes from baseline in American Urological Association Symptom Scale (AUA SS) and Post-Void Residual (PVR) bladder ultrasound. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Summary of the Columbia Suicide Severity Rating Scale (C-SSRS). [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Worsening of seizures [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Time to withdrawal [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Incidence of haematology, chemistry, and urinalysis parameters of clinical concern [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]
  • Change from baseline in haematology, chemistry and urinalysis parameters. [ Time Frame: Up to Week 156 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: February 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Retigabine IR
Open label flexible dose between 300 mg/day (Minimum) and 1200 mg/day (maximum).
Drug: Retigabine IR
Flexible dose between 300 mg/day (minimum) and 1200 mg/day (maximum)

Detailed Description:

RTG113413 is an open-label, multicentre extension study of RGB113905. This study will enrol adult subjects with partial-onset seizures (POS) who successfully completed 20 weeks of adjunctive treatment with retigabine IR (4-weeks Titration Phase and 16-weeks Flexible Dose Evaluation Phase) in the parent study, RGB113905 and who were thought to have benefitted from the treatment.

The Screening Visit (Visit 1) will be performed on the same day as the final visit of the parent study (Visit 7/Week 20). Subjects entering the extension study will initially receive the same dose of retigabine IR and concurrent antiepileptic drug (AED) as they were receiving on the final visit of the parent study. After the first week of the extension study, the subject's retigabine dose can be adjusted based on efficacy and tolerability. The overall daily dose of retigabine IR must be maintained between 300 mg/day (minimum) and 1200 mg/day (maximum). In addition, the dose and the number of concurrent AEDs can be adjusted to meet the individual needs of the subject. Retigabine IR monotherapy is not permitted. If concurrent AED therapy is removed, the subject must be withdrawn from the study.

Subjects in this study will be eligible to receive retigabine IR treatment until one of the following criteria have been met: i) regulatory approval and commercial availability of retigabine IR or ii) retigabine IR is not approved by the regulatory authorities or iii) the study is terminated by the sponsor for reasons including, but not limited to, safety issues or iv) subject is withdrawn or withdraws consent or v) subject has received retigabine IR treatment for a total of 3 years and options i-iv have not been met. After the Screening Visit, subjects will be required to attend 4 further clinic visits at Weeks 13, 26, 39, and 52 in the first year of the study and a total of 3 clinic visits at approximately 4-monthly intervals during each of the second and third year of study. Upon completion or early withdrawal, subjects will begin a 3-week taper period and then return for a follow-up visit.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has successfully completed the 20-weeks (4-weeks Titration and 16-weeks of Flexible Dose Evaluation Phases) of treatment with retigabine IR as adjunctive therapy to one of the pre-specified AEDs in the parent study RGB113905.
  • The investigator and the subject, or caregiver, if applicable, should consider it beneficial for the subject to receive continued retigabine IR therapy.
  • The subject is 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 for the entire duration of the study.
  • The subject has given written informed consent, or has a legally authorised 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 of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre- menarchal or post menopausal).
  • A female subject is eligible to enter and participate in the study if she is child-bearing potential and has a negative pregnancy test at Screening, and agrees to use one of the contraceptive methods listed in Appendix 3 of the protocol.
  • A female subject is eligible to enter and participate in the study if she 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 met any of the withdrawal criteria in the previous RGB113905 study or has clinically significant abnormal clinical laboratory or ECG findings not resolved prior to entry to the open-label extension study.
  • Is suffering from acute or progressive neurological disease, severe psychiatric disease, or severe mental abnormalities that are likely to interfere with the study objectives.
  • 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, including but not limited to: clinically significant cardiac, renal, hepatic condition, or a condition that affects the absorption, distribution, metabolism or excretion of drugs.
  • Has any abnormality on 12-lead ECG at Screening which is clinically significant in the opinion of the investigator, or has QTc (either QTcB Bazett's correction or QTcF Fridericia's correction) >500 msec or >530 msec for subjects with Bundle Branch Block or an increase in QTc of >60 msec from Baseline in the parent study.
  • Is unwilling or inability to follow the study procedures or reporting of AEs.
  • Is planning on following a ketogenic diet or planning surgery or implantation of a Vagus Nerve Stimulator (VNS) to control seizures during the study. Note: Subjects who already have a VNS implanted which is functional may be permitted to enter the study.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01336621

  Show 34 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01336621     History of Changes
Other Study ID Numbers: 113413
Study First Received: March 10, 2011
Last Updated: April 17, 2014
Health Authority: Bulgaria: Bulgarian Drug Agency
Spain: Agencia Española del Medicamento y Productos Sanitarios
Belgium: Agence Fédérale des Medicaments et des Produits de la Santé
Denmark: Lægemiddelstyrelsen
Spain:Agencia Espanola de Medicamentos y Productos Sanitarios
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Netherlands: De Centrale Commissie Mensgebonden Onderzoek
Sweden: Läkemedelsverket
Italy: Comitato Per La Sperimentazione Clinica dei Medicinali Dell'azienda Ospedaliero

Keywords provided by GlaxoSmithKline:
Partial-onset seizures
retigabine IR
Open Label Extension
GW582892
Epilepsy

Additional relevant MeSH terms:
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Ezogabine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014