Last updated: 07/17/2024 15:26:18
Long-Term Safety Study of Retigabine Immediate Release (IR) as Adjunctive Therapy in the Treatment of Adults with Partial-Onset Seizures (POS)IR
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:
Number of participants with treatment emergent adverse events (TEAEs) and serious AEs (TESAEs): Safety Population
Timeframe: Up to 5.8 years
Number of participants with AEs and SAEs: All SFUCP subjects
Timeframe: Up to 2.6 years
Number of participants withdrawn due to TEAEs
Timeframe: Up to 5.8 years
Number of participants with retinal pigmentary abnormalities
Timeframe: Up to 5.8 years
Number of participants with pigmentation of non-retinal ocular tissue(s)
Timeframe: Up to 5.8 years
Number of participants with abnormal discoloration of skin
Timeframe: Up to 5.8 years
Number of participants with a clinically significant decrease in visual acuity from initial examination
Timeframe: Up to 5.8 years
Number of participants with decrease in confrontational visual field from initial examination
Timeframe: Up to 5.8 years
Number of participants with potential clinical concern (PCC) values of change from Baseline in vital signs and weight
Timeframe: Up to 5.8 years
Change from Baseline in electrocardiogram (ECG) parameter including HR
Timeframe: Baseline and up to 5.8 years
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
Number of participants with clinical chemistry parameters of PCC
Timeframe: Up to 5.8 years
Number of participants with hematology parameters of PCC
Timeframe: Up to 5.8 years
Number of participants with urinalysis parameters of PCC
Timeframe: Up to 5.8 years
Change from Baseline in albumin and total protein
Timeframe: Baseline and up to 5.8 years
Change from Baseline in alk. phosphatase, ALT, AST, creatine kinase and LD levels
Timeframe: Baseline and up to 5.8 years
Change from Baseline in direct bilirubin, total bilirubin and creatinine
Timeframe: Baseline and up to 5.8 years
Change from Baseline in BUN/creatinine ratio
Timeframe: Baseline and up to 5.8 years
Change from Baseline in calcium, chloride, CO2, glucose, potassium, magnesium, sodium and BUN
Timeframe: Baseline and up to 5.8 years
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
Change from Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) levels
Timeframe: Baseline and up to 5.8 years
Change from Baseline in hematocrit levels
Timeframe: Baseline and up to 5.8 years
Change from Baseline in mean corpuscle hemoglobin (MCH) levels
Timeframe: Baseline and up to 5.8 years
Change from Baseline in mean corpuscle volume (MCV) and mean platelet volume (MPV) levels
Timeframe: Baseline and up to 5.8 years
Change from Baseline in RBC count
Timeframe: Up to 5.8 years
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
Change from Baseline in urine albumin creatinine ratio
Timeframe: Baseline and up to 5.8 years
Change from Baseline in urine albumin levels
Timeframe: Baseline and up to 5.8 years
Change from baseline in urine creatinine levels
Timeframe: Baseline and up to 5.8 years
Changes from Baseline in American Urological Association Symptom Scale (AUA SS) score
Timeframe: Baseline and up to 5.8 years
Change from Baseline in Post-Void Residual (PVR) bladder ultrasound urine volume
Timeframe: Baseline and up to 5.8 years
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
Number of participants experiencing new seizure types
Timeframe: Up to 5.8 years
Number of participants experiencing worsening of seizures
Timeframe: Up to 5.8 years
Duration of retigabine exposure
Timeframe: Up to 5.8 years
Number of participants with resolution of abnormal eye pigmentation after discontinuation of retigabine
Timeframe: Up to 2.6 years
Number of participants with resolution of dermatologist confirmed abnormal discoloration after discontinuation of retigabine
Timeframe: Up to 2.6 years
Time from discontinuation of retigabine to resolution of abnormal eye pigmentation
Timeframe: Up to 2.6 years
Time from discontinuation of retigabine to resolution of all dermatologist-confirmed abnormal discoloration
Timeframe: Up to 2.6 years
Secondary outcomes:
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
Percent change from Baseline in 28-day partial-onset seizure frequency
Timeframe: Baseline and up to 5.8 years
Number of participants experiencing an increase in 28-day partial-onset seizure frequency from Baseline
Timeframe: Baseline and up to 5.8 years
Number of participants who remained seizure-free
Timeframe: Up to 5.8 years
Interventions:
Enrollment:
98
Primary completion date:
2016-14-12
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Neil Brickel, Karen Hewett, Kirsty Rayner, Susan McDonald, Jeni De’Ath, Jerzy Daniluk, Kalpesh Joshi, Marie Catherine Boll, Tiamkao Somsak, Olga Vorobyeva, James Cooper.Safety of retigabine in adults with partial-onset seizures after long-term exposure: focus on unexpected ophthalmological and dermatological events.Epilepsy Behav.2020;102:106580
DOI: 10.1016/j.yebeh.2019.106580
PMID: 31731109
Medical condition
Epilepsy
Product
retigabine
Collaborators
Not applicable
Study date(s)
February 2011 to September 2017
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Bielefeld, Nordrhein-Westfalen, Germany, 33617
Status
Study Complete
Showing 1 - 6 of 31 Results
Study documents
Clinical study report
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2016-14-12
Actual study completion date
2017-13-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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