Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome
Condition: Lennox-Gastaut Syndrome
MeSH terms: Lennox Gastaut Syndrome; Syndrome
Intervention: Clobazam
Intervention description: Clobazam will be provided in 5 mg, 10 mg and 20 mg tablets and will be dispensed in bottles as needed at each visit. Bottles may be dispensed between visits if necessary. Subjects will start at a common dose level of 0.5 mg/kg, not to exceed 40 mg/day, and must maintain the dose level for 48 hours. After the first 48 hours of the treatment period, investigators will be able to increase, decrease or maintain the subject's dose, up to an approximate maximum daily dose of 2.0 mg/kg (maximum dose of 80 mg/day).
Intervention MeSH terms: Clobazam
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 267.0
Sex: All
Minimum age: 2 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Lennox-Gastaut Syndrome (LGS); Epilepsy; Drop Seizures; Clobazam

Summary:

      The objective of this study is to evaluate the long-term safety and effectiveness of
      open-label clobazam in the treatment of drop seizures in subjects with LGS.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject or subject's legally authorized representative (LAR) must sign and date
             the institutional review board (IRB)/independent ethics committee (IEC) approved
             Informed Consent Form/Health Insurance Portability and Accountability Act (HIPAA)
             Authorization (if required) prior to study participation.

          -  Previous participation in Lundbeck-sponsored LGS study.

          -  Subject must weigh ≥12.5 kilograms.

          -  Male or female subjects must have been between 2 and 60 years of age at the time of
             the enrollment in the Phase 3 double-blind study (13110A/OV1012/NCT00518713) or
             between 2 and 30 years of age at the time of the enrollment in the Phase 2
             double-blind study (13108A/OV1002/NCT00162981) study.

          -  If female:

               -  Subject 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 4 weeks prior to study entry and for
                  4 weeks following completion of the study.

               -  Subject is not breastfeeding.

               -  Subjects of childbearing potential must have a negative serum pregnancy test at
                  Study Day 1.

          -  In the investigator's opinion, parent or caregiver must be able to keep an accurate
             seizure diary.

        Exclusion Criteria:

          -  Greater than 14 days have elapsed since the subject received his/her last dose of
             study medication in the previous Lundbeck-sponsored LGS study.

          -  Subject had a serious or severe adverse event in the previous Lundbeck-sponsored LGS
             study that in the opinion of the investigator was probably or definitely related to
             clobazam use and precludes safe use of clobazam.

          -  Subject has had an anoxic episode requiring resuscitation within 6 months of study
             entry.

          -  Subject has a history of an allergic reaction or significant sensitivity to
             benzodiazepines or to any of the other ingredients in clobazam tablets.

          -  Subject is taking more than 3 concurrent anti-epileptic drugs (AEDs). NOTE: Vagal
             Nerve Stimulator (VNS) or ketogenic diet is allowed and will not be counted in the
             three allowed AEDs.

          -  Subject 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.

          -  If the subject is taking felbamate, has been taking it for less than 1 year prior to
             study entry or previous treatment with felbamate resulted in withdrawal due to liver
             or bone marrow adverse events.

          -  Subject has experienced an idiosyncratic reaction to an AED, e.g., carbamazepine with
             resulting aplastic anemia or agranulocytosis, topiramate with resulting metabolic
             acidosis, felbamate with resulting aplastic anemia or hepatic failure, or lamotrigine
             with resulting skin irritation and/or rash.

          -  Subject 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).

          -  Subject has taken or used any investigational drug or device in the 30 days prior to
             screening, with the exception of clobazam in a Lundbeck-sponsored study.

          -  Subject has a clinically significant unstable hepatic, hematological, renal,
             cardiovascular, gastrointestinal, or pulmonary disease or ongoing malignancy.

          -  Subject has a diagnosis of sleep apnea.

          -  Subject has a compromised respiratory function or severe respiratory insufficiency.

          -  Subject has a history of severe muscle weakness, including myasthenia gravis.

          -  Subject has a clinically significant abnormal laboratory value or electrocardiogram
             (ECG) abnormality.

          -  Subject has progressive lesion confirmed by magnetic resonance imaging (MRI) or
             computed tomography (CT) scan.

          -  Subject has a history of drug or alcohol abuse.

          -  Subject has a history of poor compliance on past antiepileptic therapy.

          -  Subject has inadequate supervision by parent or guardian.

          -  For any reason, the subject is considered by the investigator to be an unsuitable
             candidate for the study.