Efficacy, Safety and Tolerability of TRI476 (Oxcarbazepine) in Children With Inadequately Controlled Partial Onset Seizures

A Multicentre, Randomized, Double-blind, Placebo Controlled, Parallel-group Study in Children With Inadequately Controlled Partial Onset Seizures to Investigate Efficacy, Safety and Tolerability of TRI476 (Oxcarbazepine) as Adjunctive Therapy

This study is designed to provide short term efficacy and safety data of TRI476 in children with inadequately-controlled partial seizures. Patients will be randomized into either drug treatment or placebo group at 1:1 ratio, and receive their respective treatment for 8 weeks. The purpose of study is to confirm that TRI476 as adjunctive therapy is effective and safe.

Study Overview

• Status: Completed
• Conditions: Partial Onset Seizures
• Intervention / Treatment: Drug: TRI476; Drug: Benzodiazepines; Drug: Placebo to TRI476

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Gifu, Japan, 502-8558
    • Novartis Investigative Site
  • Niigata, Japan, 950-2085
    • Novartis Investigative Site
  • Saitama, Japan, 339-8551
    • Novartis Investigative Site
  • Shizuoka, Japan, 420-8688
    • Novartis Investigative Site
  • Yamagata, Japan, 990-0876
    • Novartis Investigative Site
  • Aichi
    • Nagoya-shi, Aichi, Japan, 460-0004
      • Novartis Investigative Site
    • Ohbu, Aichi, Japan, 474-0031
      • Novartis Investigative Site
  • Ehime
    • Matsuyama, Ehime, Japan, 790-8524
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 814-0180
      • Novartis Investigative Site
  • Hokkaido
    • Kameda-gun, Hokkaido, Japan, 041-1111
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 060-8648
      • Novartis Investigative Site
  • Hyogo
    • Himeji, Hyogo, Japan, 670-8540
      • Novartis Investigative Site
    • Kobe, Hyogo, Japan, 658-0032
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 244-0842
      • Novartis Investigative Site
  • Kumamoto
    • Koshi-city, Kumamoto, Japan, 861-1196
      • Novartis Investigative Site
  • Niigata
    • Kashiwazaki, Niigata, Japan, 945-8585
      • Novartis Investigative Site
  • Oita
    • Yufu, Oita, Japan, 879-5593
      • Novartis Investigative Site
  • Okayama
    • Kurashiki, Okayama, Japan, 710-8522
      • Novartis Investigative Site
    • Okayama-city, Okayama, Japan, 700-8558
      • Novartis Investigative Site
  • Osaka
    • Neyagawa, Osaka, Japan, 572-0085
      • Novartis Investigative Site
  • Saitama
    • Higashimatsuyama-shi, Saitama, Japan, 355-0008
      • Novartis Investigative Site
  • Shiga
    • Moriyama-shi, Shiga, Japan, 524-0022
      • Novartis Investigative Site
  • Tochigi
    • Shimotsuke-city, Tochigi, Japan, 329-0498
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Novartis Investigative Site
  • Yamanashi
    • Chuo-city, Yamanashi, Japan, 409-3898
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female outpatients, aged 4 to 14 years (inclusive), with a minimum body weight of 15 kg.
• A diagnosis of partial onset seizures, which include the seizure subtypes of simple, complex, and secondarily generalized seizures (based on the International League Against Epilepsy (ILAE) Classification, as modified in 1981).

Exclusion Criteria:

• A document history of generalized status epileptics in the past 6 months.
• Seizures having a metabolic, neoplastic, or active infectious origin.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRI476; Participants received TRI476 based on body weight with titration up to the maintenance dose, in addition to their traditional antiepileptics dosage.	Drug: TRI476; TRI476 oral suspension doses, based on body weight twice daily; Drug: Benzodiazepines; Benzodiazepines could be used as needed as rescue medication during the duration of the study.
Placebo Comparator: Placebo; Participants received placebo to TRI476 without any adjustment to the dosing regimen, in addition to their traditional antiepileptics dosage.	Drug: Benzodiazepines; Benzodiazepines could be used as needed as rescue medication during the duration of the study.; Drug: Placebo to TRI476; Placebo oral suspension, taken twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Double-blind Phase, by Treatment Group	Percent change in partial onset seizure frequency per 28 days during the double-blind phase from the screening phase, was calculated according to the following formula: "Percent change in partial onset seizure frequency per 28 days from the screening phase" = (partial onset seizure frequency per 28 days during the double-blind phase - partial onset seizure frequency per 28 days during the screening phase) / partial onset seizure frequency per 28 days during the double-blind phase x 100 "Partial onset seizure frequency per 28 days" = Number of partial onset seizures during each phase (screening phase or double-blind phase) / number of days during the screening or double-blind phase × 28.	screening and 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial Seizure Frequency Per 28 Days, by Study Period (Every 28 Days) and Treatment Group	Partial onset seizure frequency per 28 days during a period between baseline and Week 4 was measured. Partial onset seizure frequency per 28 days (count/28 days)" = Number of partial onset seizures during each phase (screening phase or double-blind phase) / Number of days during the phase x 28.	baseline, 28 days and 56 days
Percent of Participants With Response During Double-blind Phase, by Treatment Group	Responder rate was defined as the percent of participants with an at least 50% reduction in partial onset seizure frequency per 28 days from the screening phase.	screening to 28 days
Percent Change in Partial Onset Seizure Frequency During the Double-blind Phase by Seizure Type	Percent change in seizure frequency from baseline = 100 (T-B)/B, B=Seizure frequency per 28 days during baseline phase, T=Seizure frequency per 28 days during the double-blind phase. Seizure frequency per 28 days is calculated as: (seizure frequency during the double-blind phase / the number of days the seizure information were provided) x 28. Only patients with both baseline and corresponding post-baseline values are included.	28 days
Number of Participants With Clinical Global Impression of Change (CGIC) at Final Assessment, by Treatment Group	Clinical Global Impression of Change (CGI) is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse).	56 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (Estimate): September 11, 2009

Study Record Updates

• Last Update Posted (Estimate): July 16, 2014
• Last Update Submitted That Met QC Criteria: July 9, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: child; Seizures; oxcarbazepine
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures
• Other Study ID Numbers: CTRI476B1301