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Assessment of the Efficacy and Safety of 2 Doses of Retigabine Immediate Release (900 mg/Day and 600 mg/Day) Used as Adjunctive Therapy in Adult Asian Subjects With Drug-resistant Partial-onset Seizures

This study has been terminated.
(Registration of the medicine is no longer being pursued in South Korea, Taiwan or Vietnam)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01648101
First received: June 28, 2012
Last updated: September 4, 2014
Last verified: August 2014
Results First Received: August 14, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Epilepsy
Interventions: Drug: Retigabine 900mg/day
Drug: Retigabine 600mg/day
Other: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants with drug-resistant partial-onset seizures (POS) who were taking 1, 2, or 3 antiepileptic drugs (AEDs) with or without vagus nerve stimulator (VNS); had a 28-day total POS frequency rate >=4 seizures; and did not have a period of >=21 consecutive days without a POS over the 8-week Baseline Phase were enrolled in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
76 participants (par.) were randomized to study treatment; 75 par. comprised the Intent-to-Treat Population (par. who were randomly assigned to treatment, received >=1 dose/any portion of a dose of study medication, had Baseline [BL] seizure data, and had >=1 post-BL seizure record between the Titration Phase and the end of the Maintenance Phase).

Reporting Groups
  Description
Placebo Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Retigabine 600 mg Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Retigabine 900 mg Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.

Participant Flow for 4 periods

Period 1:   Titration Phase (4 Weeks)
    Placebo     Retigabine 600 mg     Retigabine 900 mg  
STARTED     25     26     24  
COMPLETED     23     23     18  
NOT COMPLETED     2     3     6  
Protocol Violation                 2                 1                 2  
Adverse Event                 0                 2                 3  
Reached Protocol Defined Criteria                 0                 0                 1  

Period 2:   Maintenance Phase (12 Weeks)
    Placebo     Retigabine 600 mg     Retigabine 900 mg  
STARTED     23     23     18  
COMPLETED     20     20     12  
NOT COMPLETED     3     3     6  
Withdrew Consent                 1                 0                 1  
Lack of Efficacy                 1                 0                 1  
Adverse Event                 1                 3                 4  

Period 3:   Transition Phase (4 Weeks)
    Placebo     Retigabine 600 mg     Retigabine 900 mg  
STARTED     17 [1]   18 [1]   9 [1]
COMPLETED     12     13     5  
NOT COMPLETED     5     5     4  
Adverse Event                 4                 3                 2  
Lack of Efficacy                 0                 2                 0  
Withdrawal by Subject                 0                 0                 2  
Study Terminated                 1                 0                 0  
[1] After completing the MP, only those par. that chose to enter the OLE study started the TnP

Period 4:   Taper/Follow-up Phase (4 Weeks)
    Placebo     Retigabine 600 mg     Retigabine 900 mg  
STARTED     1 [1]   2 [1]   3 [1]
COMPLETED     1     1     3  
NOT COMPLETED     0     1     0  
Lack of Efficacy                 0                 1                 0  
[1] Includes only those par. who completed the Titration + MN phase, but opted not to enroll in the OLE



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Retigabine 900 mg Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of RTG 300 mg/day that increased by 150 mg/day per week until a target dose of 900 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 900 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 900 mg/day for 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Retigabine 600 mg Participants entered a 16-week TrP consisting of a 4-week TiP and a 12-week MP. In the TiP, participants received a starting dose of retigabine (RTG) 300 mg/day that increased by 150 mg/day per week until a target dose of 600 mg/day was reached. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the TaP/FUP. Participants who tolerated titration entered the MP and continued to receive 600 mg/day for 12 weeks. After completing the MP, participants who opted to enroll in the OLE study entered the 4-week TnP. In the TnP, participants received RTG 600 mg/day for 3 weeks and RTG 750 mg/day in the last week. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Placebo Participants entered a 16-week Treatment Phase (TrP) consisting of a 4-week Titration Phase (TiP) and a 12-week Maintenance Phase (MP). In the TiP, participants received matching placebo in increasing doses. Participants that could not tolerate the titration or withdrew were discontinued from the study and entered the Taper/Follow-up Phase (TaP/FUP). Participants who tolerated titration entered the MP and continued to receive the same dose regimen for 12 weeks. After completing the MP, participants who opted to enroll in the open-label extension (OLE) study entered the 4-week Transition Phase (TnP). In the TnP, participants received active retigabine in increasing doses starting at 300 milligrams per day (mg/day), 450 mg/day, 600 mg/day, and 750 mg/day, respectively, in each of 4 weeks. Participants that did not enroll in the OLE study completed a 3-week TaP and 1 week of FUP.
Total Total of all reporting groups

Baseline Measures
    Retigabine 900 mg     Retigabine 600 mg     Placebo     Total  
Number of Participants  
[units: participants]
  24     26     25     75  
Age [1]
[units: Years]
Mean ± Standard Deviation
  36.0  ± 9.43     37.1  ± 10.90     36.3  ± 13.50     36.5  ± 11.27  
Gender [1]
[units: Participants]
       
Female     10     10     10     30  
Male     14     16     15     45  
Race/Ethnicity, Customized [1]
[units: Participants]
       
Asian - East Asian Heritage     17     16     15     48  
Asian - South East Asian Heritage     7     10     10     27  
[1] Baseline data are reported for members of the Safety Population: all randomized participants who received at least one dose of study medication.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Placebo and Retigabine 900 mg Responders During the Maintenance Phase (MP)   [ Time Frame: Baseline (BL); Week 4 up to Week 16 ]

2.  Secondary:   Number of Placebo and Retigabine 600 mg Responders During the MP   [ Time Frame: Baseline; Week 4 up to Week 16 ]

3.  Secondary:   Number of Responders From the BP to the Treatment Phase (TrP)   [ Time Frame: From Baseline up to Week 16 ]

4.  Secondary:   Percent Change From Baseline in the 28-day Total POS Frequency During the MP   [ Time Frame: Baseline; Week 4 up to Week 16 ]

5.  Secondary:   Percent Change From Baseline in the 28-day Total POS Frequency During the TrP   [ Time Frame: From Baseline up to Week 16 ]

6.  Secondary:   Percent Change From Baseline in the 28-day Total POS Frequency During the MP Categorized as: no Change/Increase, >0% to <50% Decrease, 50% to 75% Decrease, and >75% to 100% Decrease   [ Time Frame: Baseline; Week 4 up to Week 16 ]

7.  Secondary:   Percent Change From Baseline in 28 Day Total POS Frequency During the TrP Categorized as: no Change/Increase, >0% to <50% Decrease, 50% to 75% Decrease, and >75% to 100% Decrease   [ Time Frame: From Baseline up to Week 16 ]

8.  Secondary:   Percent Change From Baseline in the 28-day Total POS Frequency During the MP Categorized as: >25% Increase and 0% to 25% Increase   [ Time Frame: Baseline; Week 4 up to Week 16 ]

9.  Secondary:   Percent Change From Baseline in the 28-day Total POS Frequency During the TrP Categorized as: >25% Increase and 0% to 25% Increase   [ Time Frame: From Baseline up to Week 16 ]

10.  Secondary:   Number of Participants Who Were Seizure Free During the MP, ITT Population   [ Time Frame: Baseline; Week 4 up to Week 16 ]

11.  Secondary:   Number of Participants Who Were Seizure Free During the TrP   [ Time Frame: From Baseline up to Week 16 ]

12.  Secondary:   Percentage of Seizure-free Days in the MP   [ Time Frame: From Week 4 up to Week 16 ]

13.  Secondary:   Percentage of Seizure-free Days in the TrP   [ Time Frame: From Baseline up to Week 16 ]

14.  Secondary:   Incidence of New Seizure Types During the TrP in Participants Without a History of the Indicated Seizure Types at Baseline   [ Time Frame: From Baseline up to Week 16 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
RTG114855 was designed for registration of retigabine as add-on treatment of drug-resistant POS in South Korea/Taiwan/ Vietnam. GSK decided not to pursue registration in these countries and terminated the study early based on new safety information.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01648101     History of Changes
Other Study ID Numbers: 114855
Study First Received: June 28, 2012
Results First Received: August 14, 2014
Last Updated: September 4, 2014
Health Authority: Korea: Food and Drug Administration
Taiwan: Food and Drug Administration, Department of Health, Executive Yuan
Singapore: Health Sciences Authority
Philippines: Bureau of Food and Drugs
Thailand: International Affairs and Investigational New Drug Section, Drug Control Division, FDA
Hong Kong: Department of Health
Malaysia: National Pharmaceutical Control Bureau
Vietnam: Ministry of Health of Vietnam