Lennox-Gastaut SyndromePhase 3LGSNCT01160770

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

A Phase 3 study testing Clobazam in people with Lennox-Gastaut Syndrome, run by Lundbeck LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 2 to 60 years
Conditions the study is for: Lennox-Gastaut Syndrome
What is being tested?: Clobazam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 267 participants
Where: No sites listed yet
Study dates: Dec 2005to Feb 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 60 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

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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.

Who cannot join

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.

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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.

About this study

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.

Read the 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.

Conditions: Lennox-Gastaut Syndrome
Being tested: Clobazam
Keywords: Lennox-Gastaut Syndrome (LGS), Epilepsy, Drop Seizures, Clobazam
Medical subject headings: Lennox Gastaut Syndrome, Epilepsy, Syncope

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ClobazamDrug
Also called Aedon, Antacastill, Castilium, Clarmyl, Frisium, Karidium, Mefrilan, Mystan, Noiafren, Onfi, Psiton, Psyton, Sentil, Seryl, Urbadan, Urbanil, Urbanol, Urbanyl.
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).

Study groups in NCT01160770
Study group	Role	What they receive
Clobazam	Experimental	Not described Receives: Drug: Clobazam

What is being measured

The primary outcome is the main question the study is designed to answer.

Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the 7-day Assessment
Number of drop seizures was obtained from seizure diaries
Measured: Baseline to month 36
Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the Last 30-day Assessment
Number of drop seizures was obtained from seizure diaries
Measured: Baseline to month 36

Secondary outcomes (4)

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
Number of drop seizures obtained from seizure diaries
Measured: 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
Number of drop seizures obtained from seizure diaries
Measured: Baseline to month 36
Investigator Global Evaluations of the Patient's Overall Change in Symptoms
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".
Measured: Baseline to month 36
Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms
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".
Measured: Baseline to month 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2005Feb 2012

First posted12 Jul 2010 (estimated)
Study startDec 2005
Primary completionFeb 2012
Study completionFeb 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Lennox-Gastaut SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 267 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01160770
Sponsor's protocol ID: 13109A
Other IDs: OV1004
Acronym: LGS
Status last verified: Feb 2018
First submitted: 18 Jun 2010
Last updated: 21 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Ng YT, Conry J, Paolicchi J, Kernitsky L, Mitchell W, Drummond R, Isojarvi J, Lee D, Owen R; OV-1004 study investigators. Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study. Epilepsy Behav. 2012 Dec;25(4):687-94. doi: 10.1016/j.yebeh.2012.09.039. Epub 2012 Nov 7.
PubMed 23141144
Ng YT, Conry J, Kernitsky L, Mitchell W, Veidemanis R, Drummond R, Muniz R, Isojarvi J, Lee D, Paolicchi J. Long-Term Safety and Efficacy of Clobazam for Lennox-Gastaut Syndrome: Final Results of an Open-Label Extension Study. Late-Breaking Abstract #1.363 presented at the 66th annual meeting of the American Epilepsy Society, Nov. 30-Dec. 4, 2012, San Diego, California.
Gidal BE, Wechsler RT, Sankar R, Montouris GD, White HS, Cloyd JC, Kane MC, Peng G, Tworek DM, Shen V, Isojarvi J. Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study. Neurology. 2016 Oct 25;87(17):1806-1812. doi: 10.1212/WNL.0000000000003253. Epub 2016 Sep 28.
PubMed 27683846

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
Not yet recruitingPhase 4
A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS
Lennox-Gastaut Syndrome
Enrolling by invitationPhase 3
A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
Developmental and Epileptic Encephalopathy
RecruitingPhase 3
An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
Lennox Gastaut Syndrome
Enrolling by invitation
Clinical Utility of Reduced EEG Home Monitoring in Fenfluramine Titration for Dravet and LGS
Dravet Syndrome (DS), Lennox Gastaut Syndrome (LGS)

All Lennox-Gastaut Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome
ClinicalTrials.gov ID: NCT01160770
Acronym / sponsor ID: LGS / 13109A
Conditions: Lennox-Gastaut Syndrome
Keywords: Lennox-Gastaut Syndrome (LGS), Epilepsy, Drop Seizures, Clobazam
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 267 participants (actual)
Lead sponsor: Lundbeck LLCIndustry (pharma, biotech, devices)
Study start: Dec 2005
Primary completion: Feb 2012 (actual)
Study completion: Feb 2012 (actual)
First posted: 12 Jul 2010 (estimated)
Results: Posted 6 May 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Clobazam	Experimental	Drug: Clobazam

Who may qualify

Ages: 2 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (9 listed)

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:

Key exclusion criteria (20 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ClobazamAlso: Aedon, Antacastill, Castilium, Clarmyl, Frisium, Karidium, Mefrilan, Mystan, Noiafren, Onfi, Psiton, Psyton, Sentil, Seryl, Urbadan, Urbanil, Urbanol, Urbanyl.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).	Drug	Clobazam

Primary outcome

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
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

4 secondary outcomes

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
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
Investigator Global Evaluations of the Patient's Overall Change in Symptoms
Time frame: Baseline to month 36
Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms
Time frame: Baseline to month 36

Results and safety

Results posted to the registry on 6 May 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Clobazam	267	188

Primary outcome: Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the 7-day Assessment

Time frame: Baseline to month 36. Median (Full Range). Unit: percentage of drop seizures

Measure	Clobazam n = 113
Value	92.3 (-588 to 100)

Primary outcome: Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the Last 30-day Assessment

Time frame: Baseline to month 36. Median (Full Range). Unit: percentage of drop seizures

Measure	Clobazam n = 121
Value	92.7 (-752 to 100)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: The protocol was written to go up to 60 months treatment however a percentage of patients went beyond 60 months until study completion when commercial product was made available.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Clobazam	115 of 267 (43.1%)	241 of 267 (90.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23141144Ng YT, Conry J, Paolicchi J, Kernitsky L, Mitchell W, Drummond R, Isojarvi J, Lee D, Owen R; OV-1004 study investigators. Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study. Epilepsy Behav. 2012 Dec;25(4):687-94. doi: 10.1016/j.yebeh.2012.09.039. Epub 2012 Nov 7.
Results publicationNg YT, Conry J, Kernitsky L, Mitchell W, Veidemanis R, Drummond R, Muniz R, Isojarvi J, Lee D, Paolicchi J. Long-Term Safety and Efficacy of Clobazam for Lennox-Gastaut Syndrome: Final Results of an Open-Label Extension Study. Late-Breaking Abstract #1.363 presented at the 66th annual meeting of the American Epilepsy Society, Nov. 30-Dec. 4, 2012, San Diego, California.
Derived from this study: PubMed 27683846Gidal BE, Wechsler RT, Sankar R, Montouris GD, White HS, Cloyd JC, Kane MC, Peng G, Tworek DM, Shen V, Isojarvi J. Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study. Neurology. 2016 Oct 25;87(17):1806-1812. doi: 10.1212/WNL.0000000000003253. Epub 2016 Sep 28.

Related trials for Lennox-Gastaut Syndrome

RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
Not yet recruitingPhase 4
A Study to Investigate the Effect of Gradual Titration to Optimize Cannabidiol Treatment in Adults With LGS
Lennox-Gastaut Syndrome
Enrolling by invitationPhase 3
A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
Developmental and Epileptic Encephalopathy
RecruitingPhase 3
An Efficacy and Safety Study of Clemizole HCl in Patients With Lennox-Gastaut Syndrome
Lennox Gastaut Syndrome
Enrolling by invitation
Clinical Utility of Reduced EEG Home Monitoring in Fenfluramine Titration for Dravet and LGS
Dravet Syndrome (DS), Lennox Gastaut Syndrome (LGS)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Email contact via H. Lundbeck A/S study director

LundbeckClinicalTrials@lundbeck.com

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clobazam in people with Lennox-Gastaut Syndrome, run by Lundbeck LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the 7-day Assessment (time frame: Baseline to month 36). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01160770, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2018.