Clinical trial NCT01336621: Long-Term Safety Study of Retigabine Immediate Release (IR) as Adjunctive Therapy in the Treatment of Adults With Partial-Onset Seizures (POS)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Partial-onset seizures
retigabine IR
Open Label Extension
GW582892
Epilepsy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-04-18
Enrollment: 98
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 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.

Detailed description: RTG113413 is an open-label, multicentre extension study of RGB113905. This study will enroll 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 If concurrent AED therapy is removed, the subject must be withdrawn from the study.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: 1) regulatory approval and commercial availability of retigabine IR or 2) retigabine IR is not approved by the regulatory authorities or 3) the study is terminated by the sponsor for reasons including, but not limited to, safety issues or 4) subject is withdrawn or withdraws consent or 5) 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 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 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 of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre- menarcheal 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs (TESAEs): Safety Population
timeFrame: Up to 5.8 years
measure: Number of Participants With AEs and SAEs: All SFUCP Subjects
timeFrame: Up to 2.6 years
measure: Number of Participants Withdrawn Due to TEAEs
timeFrame: Up to 5.8 years
measure: Number of Participants With Retinal Pigmentary Abnormalities
timeFrame: Up to 5.8 years
measure: Number of Participants With Pigmentation of Non-retinal Ocular Tissue(s)
timeFrame: Up to 5.8 years
measure: Number of Participants With Abnormal Discoloration of Skin
timeFrame: Up to 5.8 years
measure: Number of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination
timeFrame: Up to 5.8 years
measure: Number of Participants With Decrease in Confrontational Visual Field From Initial Examination
timeFrame: Up to 5.8 years
measure: Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline in Vital Signs and Weight
timeFrame: Up to 5.8 years
measure: Change From Baseline in Electrocardiogram (ECG) Parameter Including HR
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in ECG Parameter Including PR Interval, QRS Duration, Uncorrected QT Interval, Corrected QT by Bazett's Formula (QTcB), Corrected QT by Fridericia's Formula (QTcF) and RR Interval
timeFrame: Baseline and up to 5.8 years
measure: Number of Participants With Clinical Chemistry Parameters of PCC
timeFrame: Up to 5.8 years
measure: Number of Participants With Hematology Parameters of PCC
timeFrame: Up to 5.8 years
measure: Number of Participants With Urinalysis Parameters of PCC
timeFrame: Up to 5.8 years
measure: Change From Baseline in Albumin and Total Protein
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Alk. Phosphatase, ALT, AST, Creatine Kinase and LD Levels
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Direct Bilirubin, Total Bilirubin and Creatinine
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in BUN/Creatinine Ratio
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Calcium, Chloride, CO2, Glucose, Potassium, Magnesium, Sodium and BUN
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Absolute Basophils, Absolute Eosinophils, Absolute Lymphocytes, Absolute Monocytes, Absolute Total Neutrophils, Platelet Count and WBC Count
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Levels
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Hematocrit Levels
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Levels
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV) Levels
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in RBC Count
timeFrame: Up to 5.8 years
measure: Change From Baseline in Percent Basophils, Percent Eosinophils, Percent Lymphocytes, Percent Monocytes, Percent Neutrophils and RBC Distribution Width (RDW) Levels
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Urine Albumin Creatinine Ratio
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Urine Albumin Levels
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Urine Creatinine Levels
timeFrame: Baseline and up to 5.8 years
measure: Changes From Baseline in American Urological Association Symptom Scale (AUA SS) Score
timeFrame: Baseline and up to 5.8 years
measure: Change From Baseline in Post-Void Residual (PVR) Bladder Ultrasound Urine Volume
timeFrame: Baseline and up to 5.8 years
measure: Number of Participants With Suicidal Ideation or Behavior Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Up to 5.8 years
measure: Number of Participants Experiencing New Seizure Types
timeFrame: Up to 5.8 years
measure: Number of Participants Experiencing Worsening of Seizures
timeFrame: Up to 5.8 years
measure: Duration of Retigabine Exposure
timeFrame: Up to 5.8 years
measure: Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of Retigabine
timeFrame: Up to 2.6 years
measure: Number of Participants With Resolution of Dermatologist Confirmed Abnormal Discoloration After Discontinuation of Retigabine
timeFrame: Up to 2.6 years
measure: Time From Discontinuation of Retigabine to Resolution of Abnormal Eye Pigmentation
timeFrame: Up to 2.6 years
measure: Time From Discontinuation of Retigabine to Resolution of All Dermatologist-confirmed Abnormal Discoloration
timeFrame: Up to 2.6 years
Secondary outcomes:
measure: Number of Participants Experiencing a 0 to <25, 25 to <50, 50 to <75 and 75 to 100 Percent Reduction in 28 Day POS Frequency From Baseline
timeFrame: Baseline and up to 5.8 years
measure: Percent Change From Baseline in 28-day Partial-onset Seizure Frequency
timeFrame: Baseline and up to 5.8 years
measure: Number of Participants Experiencing an Increase in 28-day Partial-onset Seizure Frequency From Baseline
timeFrame: Baseline and up to 5.8 years
measure: Number of Participants Who Remained Seizure-free
timeFrame: Up to 5.8 years
Other outcomes:
Locations:
city: Gent
country: Belgium
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: Limoges
country: France
facility: GSK Investigational Site
city: Strasbourg Cedex
country: France
facility: GSK Investigational Site
city: Bielefeld
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
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: Pisa
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Heemstede
country: Netherlands
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: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Dnepropetrovsk
country: Ukraine
facility: GSK Investigational Site
city: Lugansk
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: