| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10048816 |
| E.1.2 | Term | Lennox-Gastaut syndrome |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To determine the long-term safety and effectiveness of open-label clobazam in
the treatment of seizures in subjects with Lennox-Gastaut Syndrome (LGS).
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| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) The subject or subject’s LAR must sign and date the IRB/IEC approved Informed Consent Form/HIPAA Authorization (if required) prior to study participation.
2) Previous participation in Ovation-sponsored LGS study.
3) Subject must weigh greater or equal 12.5 kilograms.
4) 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 (protocol number OV-1012) or between 2 and 30 years of age at the time of the enrollment in the Phase 2 double-blind study (protocol number OV-1002) study.
5) If female:
a. 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.
b. Subject is not breastfeeding.
c. Subjects of childbearing potential must have a negative serum pregnancy test at Study Day 1.
6) In the investigator’s opinion, parent or caregiver must be able to keep an accurate seizure diary.
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| E.4 | Principal exclusion criteria |
1) Greater than 14 days have elapsed since the subject received his/her last dose of study medication in the previous Ovation-sponsored LGS study.
2) Subject had a serious or severe adverse event in the previous Ovation sponsored LGS study that in the opinion of the investigator was probably or definitely related to clobazam use and precludes safe use of clobazam.
3) Subject has had an anoxic episode requiring resuscitation within 6 months of study entry.
4) Subject has a history of an allergic reaction or significant sensitivity to benzodiazepines or to any of the other ingredients in clobazam tablets.
5) Subject is taking more than 3 concurrent AEDs. NOTE: Vagal Nerve Stimulator (VNS) or ketogenic diet is allowed and will not be counted in the three allowed AEDs.
6) 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.
7) 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.
8) 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.
9) Subject has shown any clinically significant history of hyper-sensitivity to CNS-active medications leading to neurobehavioral aberrations (e.g., increased biting, scratching, kicking, or hitting).
10) Subject has taken or used any investigational drug or device in the 30 days prior to screening, with the exception of clobazam in an Ovation-sponsored study.
11) Subject has a clinically significant unstable hepatic, hematological, renal, cardiovascular, gastrointestinal, or pulmonary disease or ongoing malignancy.
12) Subject has a diagnosis of sleep apnea.
13) Subject has a compromised respiratory function or severe respiratory insufficiency.
14) Subject has a history of severe muscle weakness, including myasthenia gravis.
15) Subject has a clinically significant abnormal laboratory value or electrocardiogram (ECG) abnormality.
16) Subject has progressive lesion confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
17) Subject has a history of drug or alcohol abuse.
18) Subject has a history of poor compliance on past antiepileptic therapy.
19) Subject has inadequate supervision by parent or guardian.
20) For any reason, the subject is considered by the investigator to be an unsuitable candidate for the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percent reduction at various time intervals in number of drop seizures (average per week in the week preceding each study visit) compared to the baseline period of the study from which the subject rolled over (previous Ovation sponsored study) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 15 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 21 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
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