Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000600246
Ethics application status
Approved
Date submitted
17/07/2009
Date registered
20/07/2009
Date last updated
17/04/2020
Date data sharing statement initially provided
17/04/2020
Date results information initially provided
17/04/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Carisbamate Retention Study (CaReS): Comparative Study on the Long Term Effectiveness, Safety and Tolerability of Carisbamate Compared to Two Other Frequently Prescribed Anti-Epileptic Drugs (AEDs) in Patients With Epilepsy.
Scientific title
A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Evaluate the Retention Rate, Efficacy, Safety, and Tolerability of Carisbamate, Topiramate and Levetiracetam as Adjunctive Therapy in Subjects With Partial Onset Seizures
Secondary ID [1] 934 0
http://www.clinicaltrials.gov identifier NCT00563459
Universal Trial Number (UTN)
Trial acronym
CARISEPY3007
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy Seizures 237291 0
Condition category
Condition code
Neurological 239613 239613 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
carisbamate oral capsule, daily dose range 400mg to 1200mg in 2 equally divided daily doses for twelve months. Actual dose is determined by the investigator on a case by case basis depending on participant tolerability and efficacy. If the patient then enters the open label carisbamate phase, treatment will continue until registration in Australia.
Intervention code [1] 236965 0
Treatment: Drugs
Comparator / control treatment
Topiramate oral capsule, daily dose range 200mg to 400mg in 2 equally divided daily doses for twelve months. Actual dose is determined by the investigator on a case by case basis depending on participant tolerability and efficacy.

Levetiracetam oral capsule, daily dose range 1000mg to 3000mg in 2 equally divided daily doses for twelve months. Actual dose is determined by the investigator on a case by case basis depending on participant tolerability and efficacy.
Control group
Active

Outcomes
Primary outcome [1] 238399 0
The primary efficacy endpoint is time from the first intake of study medication to discontinuation (all causes) of study medication during the 6 month core double-blind phase. Determined by analysis of the date of first dose to the last dose taken for discontinued patients on or before the six month time period.
Timepoint [1] 238399 0
Assessed at the six month time period following randomisation.
Secondary outcome [1] 244867 0
Cognitive side effect profiles of Carisbamate and Topiramate. Examples include memory, response time and speech changes. Determined by a variety of assessment s and questionnaires including computerised cognitive test battery and mental effects questionnaire - patient and observer.
Timepoint [1] 244867 0
Assessed at the six month and Twelve month time period following randomisation.
Secondary outcome [2] 244868 0
Neuropsychiatric side effect profiles of Carisbamate and Levetiracetam. Examples include behaviour, mood, inability to sleep, motivation and depression. Determined by a variety of assessments and questionnaires including, profiles of mood questionnaire, depression scales, mental effects questionnaire - patient and observer.
Timepoint [2] 244868 0
Assessed at the six month and Twelve month time period following randomisation.
Secondary outcome [3] 244875 0
Reasons for discontinuation among the 3 treatment arms. Discontinuation will be determined by lab assessments, seizure diary, cognitive assments, adverse event review, required background anti epileptic drug dosage changes, required investigational product dosage changes, inability to tolerate minimum investigational product dosage as outlined, patient and investigator discretion.
Timepoint [3] 244875 0
Assessed at the six month and Twelve month time period following randomisation.
Secondary outcome [4] 244876 0
Seizures rates among the 3 treatment arms as determined by review of the patient seizure diary.
Timepoint [4] 244876 0
Assessed at the six month and Twelve month time period following randomisation.
Secondary outcome [5] 244877 0
Subject reported mood states, behavioral and cognitive side effect changes among the 3 treatment arms assessed by the use of patient questionnaires.
Timepoint [5] 244877 0
Assessed at the six month and Twelve month time period following randomisation.

Eligibility
Key inclusion criteria
Patients must weigh >= 45 kg (~100lbs)
Established diagnosis, for at least 3 months prior to screening, of partial onset seizures, including simple partial motor, complex partial, or secondarily generalized seizures
At least 1 but no more than 120 partial onset seizures during the 3-month retrospective baseline period prior to screening
History of monotherapy Anti Epileptic Drug (AED) treatment failure at at least 1 but not more than 4 AEDs in the past
Females must be postmenopausal for at least 2 years, surgically sterile, abstinent, or, if sexually active, practicing an acceptable method of birth control (eg, intrauterine device, double barrier method, male partner sterilization) before entry and throughout the study
Females must have a negative serum beta chorionic gonadotropin pregnancy test result at screening/randomization
Current AED treatment with at least 1 and no more than 2 AEDs given at a stable dose 30 days prior to screening
For adolescents (as defined by local regulations), a responsible person must be available to accompany the patient to the study center at each visit, to provide reliable information for the safety and effectiveness evaluations, and to accurately and reliably dispense the study drug as directed, if required in the opinion of the investigator
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Must not have a generalized epileptic syndrome, primary generalized seizures, atonic seizures, typical or atypical absence seizures nor only simple partial type seizures with manifestations other than motor symptoms (i.e, simple partial sensory)
No history of unprovoked status epilepticus in the last 6 months prior to screening nor history of Lennox-Gastaut or West Syndrome
More than 3 days of sedative or benzodiazepine use for seizures in the 3 months months prior to screening
No clinical evidence of significant cardiac disease
Alanine transaminase (ALT) > 1.5 times the upper limit of normal or total bilirubin above the upper limit of normal at screen
No history of drug-induced liver injury, diagnosis of any form of chronic liver disease, cirrhosis, or liver cancer nor positive hepatitis serology as determined by multiantigen enzyme immunoassay (EIA)
No past or current treatment with topiramate or levetiracetam for any reason
No current use of vagal nerve stimulator
No diagnosis of psychotic disorder, bipolar disease, or major depression or other neurologic conditions, serious or medically unstable systemic disease, suicidal ideation or attempts, or homicide attempts at any time in the past 2 years
Unable to swallow solid oral dosage forms whole with the aid of water (patients may not chew, divide, dissolve, or crush the study drug)
Anyone who falls under the precautions, warnings or contraindications outlined in the local topiramate and/or local levetiracetam package insert

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Treatment, Randomized, Double Blind, parallel Group Assignment, Safety Study, active-comparator, multi-center study.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Carisbamate partial onset seizures studies lacked consistent efficacy data so trials in this indication were terminated.
Date of first participant enrolment
Anticipated
1/08/2009
Actual
15/11/2007
Date of last participant enrolment
Anticipated
Actual
3/09/2009
Date of last data collection
Anticipated
Actual
19/04/2010
Sample size
Target
600
Accrual to date
Final
89
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 1953 0
6001
Recruitment postcode(s) [2] 1954 0
5011
Recruitment postcode(s) [3] 1955 0
3168
Recruitment postcode(s) [4] 1956 0
4029
Recruitment postcode(s) [5] 1957 0
2050
Recruitment postcode(s) [6] 1958 0
3065
Recruitment postcode(s) [7] 1959 0
4558
Recruitment postcode(s) [8] 1960 0
3081
Recruitment postcode(s) [9] 1961 0
2031
Recruitment postcode(s) [10] 1962 0
5042
Recruitment postcode(s) [11] 1963 0
3065
Recruitment outside Australia
Country [1] 1888 0
India
State/province [1] 1888 0
Country [2] 1889 0
Korea, Democratic People's Republic Of
State/province [2] 1889 0
Country [3] 1890 0
United States of America
State/province [3] 1890 0
Country [4] 1891 0
Poland
State/province [4] 1891 0
Country [5] 1892 0
Belgium
State/province [5] 1892 0
Country [6] 1893 0
Czech Republic
State/province [6] 1893 0
Country [7] 1894 0
Finland
State/province [7] 1894 0
Country [8] 1895 0
France
State/province [8] 1895 0
Country [9] 1896 0
Italy
State/province [9] 1896 0
Country [10] 1897 0
South Africa
State/province [10] 1897 0
Country [11] 1898 0
Spain
State/province [11] 1898 0
Country [12] 1899 0
Turkey
State/province [12] 1899 0
Country [13] 1900 0
United Kingdom
State/province [13] 1900 0
Country [14] 1901 0
Mexico
State/province [14] 1901 0
Country [15] 1902 0
Russian Federation
State/province [15] 1902 0
Country [16] 1903 0
Argentina
State/province [16] 1903 0
Country [17] 1904 0
Portugal
State/province [17] 1904 0
Country [18] 1905 0
Taiwan, Province Of China
State/province [18] 1905 0
Country [19] 1906 0
Thailand
State/province [19] 1906 0

Funding & Sponsors
Funding source category [1] 237351 0
Commercial sector/Industry
Name [1] 237351 0
Ortho-McNeil Janssen Scientific Affairs, Limited Liability Company,(LLC)
Country [1] 237351 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Ortho-McNeil Janssen Scientific Affairs, LLC
Address
1125 Trenton-Harbourton Road
P.O. Box 200
Titusville, NJ 08560-200
Country
United States of America
Secondary sponsor category [1] 236850 0
Commercial sector/Industry
Name [1] 236850 0
Quintiles Pty Ltd
Address [1] 236850 0
Level 8 67 Albert Avenue Chatswood NSW 2067
Country [1] 236850 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239487 0
Royal Brisbane and Womens Hospital Human Research Ethics Committee Metro North District
Ethics committee address [1] 239487 0
Butterfield Street
Herston
Queensland 4029
Ethics committee country [1] 239487 0
Australia
Date submitted for ethics approval [1] 239487 0
16/03/2009
Approval date [1] 239487 0
08/05/2009
Ethics approval number [1] 239487 0
HREC/09/QRBW/58

Summary
Brief summary
This study has resumed recruitment following a protocol amendment. This is a randomized, double-blind, parallel-group, active-comparator, multi-center study. The study consists of 5 phases: pretreatment (screening), double-blind titration phase, double blind maintenance phase, a transition phase, and an open-label phase. Patients who are not eligible or choose not to enter the transition and open-label phases of the study will complete an exit phase following double-blind treatment.The primary outcome variable is long term retention rate and safety of adjunctive therapy with carisbamate vs.

topiramate and levetiracetam over a six month period. This primary endpoint is a clinically meaningful measure of efficacy, safety and tolerability over time, reflecting the therapeutic effectiveness of antiepileptic drugs (AEDs). Safety evaluations including adverse event monitoring, blood tests, and vital signs will be conducted throughout the study.The hypothesis is that the 3 study medications at a minimum will have similar treatment retention rates, but based on their distinct efficacy and side effect profiles, will have discernible differences in the rates of selected adverse events and reasons for treatment discontinuation in patients with partial onset seizures.

Patients must be on at least 1, but not more than 2, baseline AEDs for 30 days prior to screening. By end of week 8 patients must have reached the following minimum dosages of study drug to be permitted to continue: carisbamate 400 mg/day, topiramate 200 mg/day, or levetiracetam 1000 mg/day.

Double-blind phases last approximately 12 months. Carisbamate 800 mg/day, topiramate 300 mg/day and levetiracetam 2000mg/day will be administered orally in two equally divided doses.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29922 0
Address 29922 0
Country 29922 0
Phone 29922 0
Fax 29922 0
Email 29922 0
Contact person for public queries
Name 13169 0
Nick Campbell
Address 13169 0
Executive Director, Corporate Affairs
J&J Australia/New Zealand
1-5 Khartoum
North Ryde
NSW 2113
Country 13169 0
Australia
Phone 13169 0
+61 2 8875 3240
Fax 13169 0
Email 13169 0
[email protected]
Contact person for scientific queries
Name 4097 0
Dr Augusto Grinspan
Address 4097 0
Ortho-McNeil Janssen Scientific Affairs, LLC
1125 Trenton-Harbourton Road - A32509
Titusville, NJ 08560
Country 4097 0
United States of America
Phone 4097 0
+1 609 730 2702
Fax 4097 0
Email 4097 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.