Meta-Analysis Plan for Pooled Data for Studies VRX-RET-E22-303 and VRX-RET-E22-304

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01457989
First received: October 20, 2011
Last updated: October 25, 2012
Last verified: October 2012

October 20, 2011
October 25, 2012
August 2011
August 2011   (final data collection date for primary outcome measure)
Incidence of Adverse Events [ Time Frame: during open-label drug exposure up to database cutoff (max 40 months) ] [ Designated as safety issue: Yes ]
Adverse events were the primary means to assess safety.
Same as current
Complete list of historical versions of study NCT01457989 on ClinicalTrials.gov Archive Site
  • Time to Discontinuation [ Time Frame: during open-label extension up to date of discontinuation; subjects who continue in the study are censored at database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Time to discontinuation in number of days since first dose in open-label extension until subject discontinues
  • The number and percent of subjects exposed to study drug [ Time Frame: for at least 3, 6, 12, 18, 24 and 32 months ] [ Designated as safety issue: No ]
    The number and percent of subjects exposed to study drug
  • Listing of abnormal liver function test results and liver adverse events [ Time Frame: during open-label drug exposure up to database cutoff (max 40 months) ] [ Designated as safety issue: Yes ]
    Abnormal lab results if reported as adverse events or values of alkaline phosphatase, alanine transaminase, aspartate transaminase [>3, >5, >10xupper limit of normal (ULN)] or total bilirubin (>1.5, >2, >4xULN); treatment emergent adverse events related to liver function test abnormalities
  • Observed values and change from baseline summaries for American Urological Association symptom index scores, Post-Void Residual bladder ultrasound, Vital Signs and Weight [ Time Frame: baseline (parent study) and at 1, 3, 12, 24 and 36 months ] [ Designated as safety issue: Yes ]
    Univariate statistics summarizing the observed values and change from baseline, using parent study baseline value
  • Percent change from baseline in seizure frequency [ Time Frame: entire open-label extension period up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Percent change from baseline in 28-day total partial seizure frequency, using parent study baseline value.
  • Number and percent of responders [ Time Frame: entire open-label extension period up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Number and percent of responders (defined as subjects with >=50% reduction from baseline in 28-day total partial seizure frequency) using parent study baseline value
  • Number and percent of seizure free subjects [ Time Frame: during open-label drug exposure up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Percent of subjects seizure free for any 6 continuous months or longer for subjects treated for at least 6, 12 and 24 months; percent of seizure free subjects for any 12 continuous months or longer for subjects treated for at least 12 and 24 months
  • Proportion of subjects retained in the study [ Time Frame: at 3, 6, 12, 24 and 32 months after exposure to first dose in open-label extension study. ] [ Designated as safety issue: No ]
    Length of time subjects retained in OLE as summarized by proportion of subjects remaining in both studies at given timepoints.
  • Mean of average dose [ Time Frame: entire open-label drug extension period up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Mean average dose for all subjects combined and by modal dose category [the range of doses (<=750 mg/day, >750 to 1050 mg/day, >1050 mg/day) taken most frequently].
  • Time to Discontinuation [ Time Frame: during open-label extension up to date of discontinuation; subjects who continue in the study are censored at database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Time to discontinuation in number of days since first dose in open-label extension until subject discontinues
  • The number and percent of subjects exposed to study drug [ Time Frame: for at least 3, 6, 12, 18, 24 and 32 months ] [ Designated as safety issue: No ]
    The number and percent of subjects exposed to study drug
  • Listing of abnormal liver function test results and liver adverse events [ Time Frame: during open-label drug exposure up to database cutoff (max 40 months) ] [ Designated as safety issue: Yes ]
    Abnormal lab results if reported as AEs or values of alkaline phosphatase, ALT, AST (>3, >5, >10xULN) or total bilirubin (>1.5, >2, >4xULN); treatment emergent adverse events related to liver function test abnormalities
  • Observed values and change from baseline summaries for American Urological Association symptom index scores, Post-Void Residual bladder ultrasound, Vital Signs and Weight [ Time Frame: baseline (parent study) and at 1, 3, 12, 24 and 36 months ] [ Designated as safety issue: Yes ]
    Univariate statistics summarizing the observed values and change from baseline, using parent study baseline value
  • Percent change from baseline in seizure frequency [ Time Frame: entire open-label extension period up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Percent change from baseline in 28-day total partial seizure frequency, using parent study baseline value.
  • Number and percent of responders [ Time Frame: entire open-label extension period up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Number and percent of responders (defined as subjects with >=50% reduction from baseline in 28-day total partial seizure frequency) using parent study baseline value
  • Number and percent of seizure free subjects [ Time Frame: during open-label drug exposure up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Percent of subjects seizure free for any 6 continuous months or longer for subjects treated for at least 6, 12 and 24 months; percent of seizure free subjects for any 12 continuous months or longer for subjects treated for at least 12 and 24 months
  • Proportion of subjects retained in the study [ Time Frame: at 3, 6, 12, 24 and 32 months after exposure to first dose in open-label extension study. ] [ Designated as safety issue: No ]
    Length of time subjects retained in OLE as summarized by proportion of subjects remaining in both studies at given timepoints.
  • Mean of average dose [ Time Frame: entire open-label drug extension period up to database cutoff (max 40 months) ] [ Designated as safety issue: No ]
    Mean average dose for all subjects combined and by modal dose category [the range of doses (<=750 mg/day, >750 to 1050 mg/day, >1050 mg/day) taken most frequently].
Not Provided
Not Provided
 
Meta-Analysis Plan for Pooled Data for Studies VRX-RET-E22-303 and VRX-RET-E22-304
Meta-Analysis of VRX-RET-E22-303 and VRX-RET-E22-304: Two Multicenter, Open-Label, Long-Term, Safety, Tolerability and Efficacy Studies of Retigabine in Adult Epilepsy Patients With Partial-onset Seizures (Extensions of Studies VRX-RET-E22-301 and VRX-RET-E22-302)

The objective of this meta-analysis is to provide data on long-term safety and efficacy following the recent positive Committee for Medicinal Products for Human Use (CHMP) opinion for retigabine using pooled data from ongoing open-label extension (OLE) Studies VRX-RET-E22-303 and VRX-RET-E22-304.

Data from the October 2009 data-cut of ongoing Studies VRX-RET-E22-303 (Study 303) and VRX-RET-E22-304 (Study 304) will be pooled, summarized, and published with the goal of providing updated long-term safety and efficacy information for subjects and prescribers following the recent positive CHMP opinion for retigabine for adjunctive use in patients with partial seizures. Studies 303 and 304 are the open-label extensions of two Phase 3 studies (VRX-RET-E22-301 and VRX-RET-E22-302), respectively. Studies 301 and 302 were randomized, double-blind, placebo-controlled, parallel-group, multicenter studies of 600 mg and 900 mg per day (Study 302) and 1200 mg per day (Study 301). All subjects who wished to enter the OLE studies and, in the opinion of the investigator, were expected to benefit from participation in the OLEs, entered a 6-week (Study 301) or 4-week (Study 302) transition phase in which their dose of retigabine was titrated to or maintained at 400 mg TID (Study 301) or 300 mg TID (Study 302). Upon completion of the Transition phase, subjects enrolled into the extension studies. Once enrolled in the OLE, doses could be adjusted within the range of 600 mg to 1200 mg per day. Treatment in Studies 303 and 304 is planned to continue until regulatory approval and commercialization of retigabine or until the program is discontinued.

Observational
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

Adult patients with partial onset seizures who have successfully completed the transition phase of VRX-RET-E22-301 and VRX-RET-E22-302.

Epilepsy, Partial
Drug: retigabine/ezogabine
dose range up to 1200 mg/day
Other Name: Trobalt
retigabine/ezogabine
retigabine/ezogabine; dose range up to 1200 mg/day
Intervention: Drug: retigabine/ezogabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1
August 2011
August 2011   (final data collection date for primary outcome measure)

This is meta-analysis therefore Inclusion/Exclusion criteria are not applicable.

Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01457989
115476
No
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP