Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome (LGS)

February 22, 2018 updated by: Lundbeck LLC
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This multi-center, open-label study is designed to evaluate the long-term safety and effectiveness of clobazam as adjunctive therapy in subjects with LGS. Subjects enrolled in Lundbeck LLC (formerly Ovation Pharmaceuticals, Inc.) sponsored studies 13108A/OV1002/NCT00162981 and 13110A/OV1012/NCT00518713 who either completed the study or who prematurely discontinued were offered the opportunity to rollover into this open-label study. 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 48 hours, investigators will be able to increase, decrease or maintain the subject's dose, up to a maximum target daily dose of 2.0 mg/kg (maximum dose of 80 mg/day). During the treatment period, seizures will be recorded during the week preceding each study visit or 30 days immediately following each study visit (dependent on Amendment approval). The subject or subject's caregiver will record daily counts of seizures, including drop seizures in the subject's seizure diary.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
267

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 56 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Clobazam
Drug: Clobazam
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).
Other Names:
  • Aedon, Antacastill, Castilium, Clarmyl, Frisium, Karidium, Mefrilan, Mystan, Noiafren, Onfi, Psiton, Psyton, Sentil, Seryl, Urbadan, Urbanil, Urbanol, Urbanyl.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the 7-day Assessment
Time Frame: Baseline to month 36
Number of drop seizures was obtained from seizure diaries
Baseline to month 36
Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the Last 30-day Assessment
Time Frame: Baseline to month 36
Number of drop seizures was obtained from seizure diaries
Baseline to month 36

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the 7-day Assessment
Time Frame: Baseline to month 36
Number of drop seizures obtained from seizure diaries
Baseline to month 36
Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the Last 30-day Assessment
Time Frame: Baseline to month 36
Number of drop seizures obtained from seizure diaries
Baseline to month 36
Investigator Global Evaluations of the Patient's Overall Change in Symptoms
Time Frame: Baseline to month 36
The physician was asked to rate the patient's overall change in symptoms since the beginning of clobazam treatment by checking "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse".
Baseline to month 36
Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms
Time Frame: Baseline to month 36
The parent/caregiver was asked to rate the patient's overall change in symptoms since the beginning of clobazam treatment by checking "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", or "very much worse".
Baseline to month 36

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lundbeck LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 18, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 12, 2010

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 21, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13109A
  • OV1004 (Other Identifier: Lundbeck LLC ((Formerly Lundbeck Inc. and before that Ovation Pharmaceuticals (OV)))

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