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.

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10048816Term: Lennox-Gastaut syndrome; ennox-Gastaut Syndrome

• Registration Number: EUCTR2007-004322-24-BG
• Lead Sponsor: Ovation Pharmaceuticals Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11-03
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified