A Long-term, Safety, Tolerability, and Efficacy Study of Retigabine Immediate-release (IR) in Asian Adults With Partial Onset Seizures

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01777139
First received: January 24, 2013
Last updated: July 24, 2014
Last verified: March 2014
  Purpose

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).


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, Tolerability, and Efficacy Study of Retigabine Immediate-release (IR) in Asian Adults With Partial Onset Seizures (Extension of Study RTG114855)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Incidence of AEs [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Safety and tolerability as assessed by incidence of adverse events (AEs).

  • Severity of AEs [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Safety and tolerability as assessed by severity of AEs

  • Proportion of subjects with AEs leading to discontinuation [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Safety and tolerability as assessed by number of AEs leading to study discontinuation

  • Vital signs [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Change from Baseline in vital signs (blood pressure and heart rate) measurements will be calculated.

  • Body weight [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Change from Baseline in body weight measurements will be calculated.

  • ECG parameters [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Changes from Baseline in electrocardiogram (ECG) parameters (heart rate, PR interval, QRS interval, and QTc interval) will be calculated.

  • Hematology parameters [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Change from Baseline in hematology parameters will be calculated.

  • Clinical chemistry parameters [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Change from Baseline in clinical chemistry parameters will be calculated.

  • Urinalysis parameters [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Change from Baseline in urinalysis parameters will be calculated.

  • AUA Symptom Index [ Time Frame: Over 4 years. ] [ Designated as safety issue: Yes ]
    The investigator will complete an American Urological Association (AUA) Symptom Index, a 7-item Likert-scored scale describing urinary bladder function. Change from Baseline in AUA Symptom Index will be calculated.

  • PVR bladder ultrasound volumes [ Time Frame: Over 4 years. ] [ Designated as safety issue: Yes ]
    The post-void residual (PVR) bladder ultrasound volumes will be performed. Change from Baseline in PVR bladder ultrasound volumes will be calculated.

  • Assessment of suicidality via use of the C-SSRSAssessment of suicidality via use of the C-SSRS [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Suicidality will be assessed based on the Columbia Suicide Severity Rating Scale (C-SSRS).

  • Time to premature study discontinuation [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Safety and tolerability as assessed by recording the time to premature study discontinuation.


Secondary Outcome Measures:
  • Proportion of responders [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Proportion of responders, defined as subjects with>=50% reduction in 28 day total partial-onset seizures (POS) frequency from Baseline (overall and by duration of exposure.

  • The 28 day total POS frequency [ Time Frame: Over 4 years. ] [ Designated as safety issue: No ]
    Percent change from Baseline in 28 day total POS frequency (overall and by duration of exposure) will be calculated.


Estimated Enrollment: 37
Study Start Date: April 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Retigabine IR
All subjects will initially receive a starting dose of retigabine IR at 900 mg/day and after the first week of the OLE study, the dose of retigabine IR may be increased or decreased in increments or decrements of decrements of 150 mg/day on weekly basis based on efficacy and tolerability. The overall daily dose of retigabine IR must be maintained between a minimum dose of 600 mg/day and a maximum dose of 1200 mg/day.
Drug: Retigabine IR
Retigabine IR tablets will be available in 5 strengths: 50 mg, 100 mg, 200 mg, 300 mg, and 400 mg.

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

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 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.
  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: NCT01777139

Locations
Korea, Republic of
GSK Investigational Site
Busan, Korea, Republic of, 602-715
GSK Investigational Site
Busan, Korea, Republic of, 612-865
GSK Investigational Site
Daegu, Korea, Republic of, 700-712
GSK Investigational Site
Daejeon, Korea, Republic of, 301-721
GSK Investigational Site
Gyeonggi-do, Korea, Republic of, 463-707
GSK Investigational Site
Seoul, Korea, Republic of, 138-736
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 135-720
GSK Investigational Site
Seoul, Korea, Republic of, 143-729
GSK Investigational Site
Seoul, Korea, Republic of, 135-710
Malaysia
GSK Investigational Site
Kuala Lumpur, Malaysia, 59100
Thailand
GSK Investigational Site
Bangkok, Thailand, 10400
GSK Investigational Site
Bangkok, Thailand, 10330
GSK Investigational Site
Khon Kaen, Thailand, 40002
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01777139     History of Changes
Other Study ID Numbers: 114873
Study First Received: January 24, 2013
Last Updated: July 24, 2014
Health Authority: Korea: Food and Drug Administration
Malaysia: Ministry of Health
Singapore: Health Sciences Authority
Thailand: Food and Drug Administration
Philippines: Bureau of Food and Drugs
Hong Kong: Department of Health
Taiwan : Food and Drug Administration
Vietnam: Ministry of Health of Vietnam

Keywords provided by GlaxoSmithKline:
Retigabine
Drug-Resistant
Epilepsy
Partial-Onset Seizures
Safety and Tolerability
Immediate Release
Long-Term
Adjunctive Therapy
Asian Subjects
Efficacy
GW582892

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 September 16, 2014