Overview

This trial is active, not recruiting.

Condition epilepsy
Treatment retigabine ir
Phase phase 3
Sponsor GlaxoSmithKline
Start date February 2011
End date December 2020
Trial size 100 participants
Trial identifier NCT01336621, 113413

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Open label flexible dose between 300 mg/day (Minimum) and 1200 mg/day (maximum).
retigabine ir
Flexible dose between 300 mg/day (minimum) and 1200 mg/day (maximum)

Primary Outcomes

Measure
Incidence of adverse events (AEs) and serious adverse events (SAEs)
time frame: Up to Week 156

Secondary Outcomes

Measure
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
The percent change from baseline in 28-day partial-onset seizure frequency during the treatment period.
time frame: Up to Week 156
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
The proportion of subjects who remain seizure free throughout the treatment period.
time frame: Up to Week 156
Proportion of subjects withdrawing due to adverse events.
time frame: Up to Week 156
Change from baseline in vital signs (blood pressure and heart rate) and weight.
time frame: Up to Week 156
Change from baseline in ECG parameters.
time frame: Up to Week 156
Changes from baseline in American Urological Association Symptom Scale (AUA SS) and Post-Void Residual (PVR) bladder ultrasound.
time frame: Up to Week 156
Summary of the Columbia Suicide Severity Rating Scale (C-SSRS).
time frame: Up to Week 156
Worsening of seizures
time frame: Up to Week 156
Time to withdrawal
time frame: Up to Week 156
Incidence of haematology, chemistry, and urinalysis parameters of clinical concern
time frame: Up to Week 156
Change from baseline in haematology, chemistry and urinalysis parameters.
time frame: Up to Week 156

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

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)
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.