Clinical trial NCT01777139: A Long-term, Safety, Tolerability, and Efficacy Study of Retigabine Immediate-release (IR) in Asian Adults With Partial Onset Seizures
Official title: A Multicentre, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of Retigabine Immediate-release (IR) in Asian Adults With Partial Onset Seizures (Extension of Study RTG114855)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epilepsy
Keywords: Retigabine
Drug-Resistant
Epilepsy
Partial-Onset Seizures
Safety and Tolerability
Immediate Release
Long-Term
Adjunctive Therapy
Asian Subjects
Efficacy
GW582892
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-01-28
Enrollment: 30
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: This is a multicentre, long-term, open-label extension (OLE) study to assess the long-term safety, tolerability and efficacy of retigabine immediate-release (IR) as adjunctive therapy in adult Asian subjects with drug-resistant partial-onset seizures (POS).

Detailed description: Subjects who successfully complete the Maintenance Phase of Study RTG114855 (parent study) and are expected to benefit from therapy with retigabine IR will be eligible for this OLE study. The study will consist of Screening (1 day), Open-Label Treatment and Follow-up (3 weeks) phase. Subjects will initially receive a starting dose of retigabine IR at 900 milligram (mg)/day and the same concurrent antiepileptic drug (AED) regimen that they were receiving at the final visit of the Transition Phase of the parent study. After the first week of the OLE study, the dose of retigabine IR may be adjusted to between 600 and 1200 mg/day, with dose adjustments in increments or decrements of 150 mg/week, based on efficacy and tolerability. In addition, the dose and number of concurrent AEDs may also be adjusted to meet each individual subject's needs. The efficacy and safety issues will be assessed throughout the study; subjects will be instructed to call the investigator if they experience any efficacy or tolerability issues between the study visits. As the duration of the study will be determined based on the following four conditions: 1) regulatory approval and commercialisation of retigabine IR; 2) retigabine IR is not approved by the regulatory authorities; 3) the study is terminated by the Sponsor for reasons including, but not limited to, safety issues; or 4) the subject is withdrawn or withdraws consent, 4 years will be considered as a guide to the duration of the study. 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. Efficacy will be assessed by calculating the percent change from Baseline (parent study) in 28-day total POS frequency for the entire open-label Treatment Phase of this OLE study. This will also be calculated based on duration of exposure. Responder rate (defined as a \>/=50% reduction from Baseline in 28-day total POS frequency) will also be summarised for the entire open-label Treatment Phase and by duration of exposure.

Eligibility criteria: Inclusion Criteria:

* The subject has successfully completed the Maintenance Phase and Transition Phase of Study RTG114855.
* The subject is expected, in the opinion of the investigator, to benefit from participation in this OLE study.
* The subject or the caregiver is able and willing to maintain an accurate and complete written daily 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 enrol and participate in the study if she is of: nonchildbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is premenarchal or 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, and postmenopausal females defined as being amenorrhoeic for \>1 year with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms). However, if indicated, this should be confirmed by oestradiol 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.
* Childbearing potential, has a negative urine or serum pregnancy test at Screening.
* Is not pregnant or lactating or planning to become pregnant during the study.

Exclusion Criteria:

* Has met any of the withdrawal criteria in the parent study (RTG114855) or has, in the opinion of the investigator, clinically significant abnormal laboratory or ECG findings that preclude entry into RTG114873.
* Is planning to begin treatment with an investigational drug (other than retigabine) and/or an experimental device for the treatment of epilepsy or any other medical condition.
* Has any medical condition that, in the investigator's judgement, 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 condition; or a condition that affects the absorption, distribution, metabolism, or excretion of drugs.
* Is unwilling or unable to follow the study procedures or reporting of AEs.
* Has active suicidal plan/intent or has had active suicidal thoughts in the past 6 months or has history of suicide attempt in the last 2 years or \>1 lifetime suicide attempt.

Primary outcomes:
measure: Number of Participants With Treatment Emergent (TE) Serious Adverse Events (SAEs) and Non-SAEs
timeFrame: Up to 4 years
measure: Percentage of Participants With TEAEs Leading to Study Discontinuation
timeFrame: Up to 4 years
measure: Number of Participants With Potential Clinical Concern (PCC) Values of Change From Baseline for Vital Signs
timeFrame: Baseline and up to 4 years
measure: Number of Participants With PCC Values of Change From Baseline for Body Weight
timeFrame: Baseline and up to 4 years
measure: Number of Participants With PCC Values of Change From Baseline for Electrocardiogram (ECG) Parameters
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Total Neutrophils, and White Blood Cell Count (WBC)
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Hematocrit
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC)
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) Level
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Mean Corpuscle Volume (MCV) and Mean Platelet Volume (MPV)
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Red Blood Cell (RBC) Count
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Red Cell Distribution Width (RDW)
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (Alk. Phosph.), Aspartate Aminotransferase (AST), Creatine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LD)
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Albumin and Total Protein
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Blood Urea Nitrogen (BUN)/Creatinine Ratio
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Calcium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicarb), Chloride, Glucose, Magnesium, Potassium, Sodium, Urea/BUN
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Urine Albumin/Creatinine Ratio
timeFrame: Baseline and up to 4 years
measure: Number of Participants With Abnormal Urinalysis Values (Categorical Data)
timeFrame: Up to 4 years
measure: Specific Gravity of Urine at Indicated Time Points
timeFrame: Up to 4 years
measure: Potential of Hydrogen (pH) of Urine at Indicated Time Points
timeFrame: Up to 4 years
measure: Change From Baseline in Urine Creatinine Concentration
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in American Urological Association (AUA) Symptom Scale Scores
timeFrame: Baseline and up to 4 years
measure: Change From Baseline in Post-void Residual (PVR) Bladder Ultrasound Volumes
timeFrame: Baseline and up to 4 years
measure: Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to 4 years
measure: Number of Participants Who Discontinued From RTG
timeFrame: Up to 4 years
measure: Percentage of Participants With Retinal Pigmentary Abnormalities
timeFrame: Up to 4 years
measure: Percentage of Participants With Pigmentation of Non-retinal Ocular Tissues
timeFrame: Up to 4 years
measure: Percentage of Participants With Dermatologist-confirmed Abnormal Discoloration
timeFrame: Up to 4 years
measure: Percentage of Participants With a Clinically Significant Decrease in Visual Acuity From Initial Examination
timeFrame: Up to 4 years
measure: Percentage of Participants With Decrease in Confrontational Visual Field From Initial Examination
timeFrame: Up to 4 years
measure: Percentage of Responders to POS Frequency
timeFrame: Up to 4 years
measure: Percent Change From Baseline in 28-day Total POS Frequency
timeFrame: Baseline and up to 4 years
measure: Number of Participants With Resolution of Abnormal Eye Pigmentation After Discontinuation of RTG
timeFrame: Up to 1.4 years
measure: Number of Participants With Resolution of Dermatologist-confirmed Abnormal Discoloration After Discontinuation of RTG
timeFrame: Up to 1.4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Daejeon
country: Korea, Republic of
facility: GSK Investigational Site
city: Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: