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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 19 March 2012
Main ID:  EUCTR2007-004322-24-LT
Date of registration: 21/01/2008
Prospective Registration: Yes
Primary sponsor: Lundbeck Inc
Public title: Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam (0.25, 0.5 and 1.0 mg/kg/day) in Patients with Lennox-Gastaut Syndrome.
Scientific title: Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam (0.25, 0.5 and 1.0 mg/kg/day) in Patients with Lennox-Gastaut Syndrome.
Date of first enrolment: 17/03/2008
Target sample size: 240
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004322-24
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no  
Phase: 
Countries of recruitment
Bulgaria Lithuania
Contacts
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Key inclusion & exclusion criteria
Inclusion criteria:
1. The patient or patient?s legally authorized representative (LAR) must sign and date the
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved
Informed Consent Form (ICF)/Health Insurance Portability and Accountability Act
(HIPAA) Authorization (if required) prior to study participation. If appropriate, the
patient will sign an Assent Form.
2. Male or female patients between 2 and 60 years of age (inclusive).
3. Patient must have been <11 years of age at the onset of LGS.
4. Patient must weigh ≥12.5 kg.
5. If female:
a. Patient is either not of childbearing potential, defined as premenarchal,
postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation,
bilateral oophorectomy or hysterectomy), or if of childbearing potential, must
comply with a method of birth control acceptable to the investigator during the
study, for at least 30 days prior to randomization and for 30 days following
completion of the study.
b. Patient is not breastfeeding.
c. Patients of childbearing potential must have a negative serum pregnancy test at
screening and a negative urine pregnancy test performed on Study Day -1.
6. Patients with LGS as evidenced by:
a. Greater than 1 type of generalized seizures, including drop seizures (atonic, tonic or
myoclonic) for at least 6 months.
b. Written documentation of having met the electroencephalogram (EEG) diagnostic
criteria for a diagnosis of LGS at some point in their history (must have abnormal
background activity accompanied by slow spike and wave pattern <2.5 Hz).
7. Patient must have experienced ≥2 drop seizures per week during the 4-week baseline
period.
8. Patient must be on at least 1 AED. Patient must be on a stable AED dosing regimen for
at least 30 days prior to screening. Neither a Vagal Nerve Stimulator (VNS) nor the
ketogenic diet will count as an AED.
9. Patients must not have been on any benzodiazepines chronically (for any indication) for
a period of at least 30 days prior to screening. Patients will be allowed to enter the study
if they have used benzodiazepines as a rescue therapy within the 30 days prior to
screening with a limit of 1 rescue per day up to an average of once per week.
10. In the investigator?s opinion, parent or caregiver must be able to keep an accurate
seizure diary.
11. In the investigator?s and parent/caregiver?s opinions, the patient is able to take study
drug.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Etiology of patient?s seizures is a progressive neurologic disease. Patients with tuberous
sclerosis will not be excluded from study participation, unless there is a progressive
tumor.
2. Patient has had an episode of status epilepticus within 12 weeks of baseline.
3. Patient has had an anoxic episode requiring resuscitation within 6 months of screening.
4. Patient has a clinically significant history of an allergic reaction or significant sensitivity
to benzodiazepines or to any of the other ingredients in clobazam tablets.
5. Patient is taking more than 3 concurrent AEDs. NOTE: VNS or ketogenic diet is
allowed and will not be counted in the three allowed AEDs.
6. Patient has been on the ketogenic diet for less than 30 days prior to screening or suffers
from frequent stooling.
7. If the patient has a VNS, the settings have not been stable for at least 30 days prior to
screening.
8. Patient has previously been treated with CLB.
9. Patient has taken corticotropins in the 6 months prior to screening.
10. Patient is currently taking long-term systemic steroids (excluding inhaled medication for
asthma treatment) or any other daily medication known to exacerbate epilepsy. An
exception will be made of prophylactic medication, for example, for idiopathic nephrotic
syndrome or asthma.
11. If the patient is taking felbamate, he/she has been taking it for less than 1 year prior to
screening.
12. Patient has experienced a clinically significant unresolved idiosyncratic reaction to an
AED, e.g., topiramate with resulting metabolic acidosis, felbamate with resulting
aplastic anemia or hepatic failure, or lamotrigine with resulting skin irritation and/or
rash.
13. Patient has shown any clinically significant history of hyper-sensitivity to central
nervous system (CNS)-active medications leading to neurobehavioral aberrations (e.g.,
increased biting, scratching, kicking or hitting).
14. If the patient is on any chronic medication, the dose has not been stable for at least 30
days prior to screening.
15. Patient has taken or used any investigational drug or device in the 30 days prior to
screening.
16. Patient has a clinically significant unstable hepatic, hematological, renal, cardiovascular,
gastrointestinal, or pulmonary disease or ongoing malignancy.
17. Patient has a diagnosis of sleep apnea.
18. Patient has compromised respiratory function or severe respiratory insufficiency.
19. Patient has a clinically significant abnormal laboratory value.
20. Patient has familial long QT syndrome, QT/QTc >500msec or a history of polymorphic
ventricular tachycardia.
21. Patient has a progressive CNS lesion confirmed by magnetic resonance imaging (MRI)
or computed tomography (CT) scan.
22. Patient has a history of drug or alcohol abuse.
23. Patient has a history of poor compliance on past antiepileptic therapy.
24. Patient has inadequate supervision by parent or guardian.
25. For any reason, the patient is considered by the investigator to be an unsuitable
candidate for the study.
26. Patient has a history of severe muscle weakness, including myasthenia gravis.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Lennox-Gastaut Syndrome
MedDRA version: 9.1 Level: LLT Classification code 10048816 Term: Lennox-Gastaut syndrome
Intervention(s)

Trade Name: Clobazam
Product Name: Clobazam Tablets 5mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Clobazam
CAS Number: 22316-47-8
Other descriptive name: Clobazam PhEur
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: 1. To determine the efficacy of clobazam (CLB) in the reduction of drop seizures at three
dose levels when compared to baseline during 12 weeks maintenance dosing in a
placebo controlled trial in patients with Lennox-Gastaut Syndrome (LGS).
2. To determine the safety of CLB when administered for up to 18 weeks at three different
dose levels in patients with LGS.
Primary end point(s): Percent reduction in number of drop seizures (average per week) from the 4-week
baseline period compared to the 12-week maintenance period.
Secondary Objective: 1. To determine the efficacy of CLB as determined by responder rates and global
evaluation of patient symptoms.
2. To determine population pharmacokinetic (PPK) parameters of CLB and its active
metabolite N-desmethylclobazam (N-CLB) at steady-state dosing of CLB in patients
with LGS and to describe sources of inter-patient variability (co-variates) including
patient demographics, concomitant antiepileptic drug (AED) medications and genotype.
3. To evaluate the development of tolerance during treatment for up to 12 weeks.
4. To determine the effect of CLB on behavior utilizing the Child Behavior Checklist
(CBCL).
5. To determine the impact of CLB on behavioral, cognitive and physical/neurologic
disability through use of the Impact of Childhood Neurologic Disability Scale (ICNDS).
Secondary Outcome(s)
Secondary ID(s)
OV-1012
Source(s) of Monetary Support
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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