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EpilepsyPhase 3NCT00518713

Clobazam in Patients With Lennox-Gastaut Syndrome

A Phase 3 study testing Clobazam Low Dose, Clobazam Medium Dose and Clobazam High Dose in people with Epilepsy and Epilepsy, Generalized, run by Lundbeck LLC at 53 sites in 5 countries.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the safety and efficacy of clobazam as adjunctive therapy in the treatment of seizures which lead to drop attacks (drop seizures) in patients 2 to 60 years of age with Lennox-Gastaut Syndrome (LGS). Patients will be enrolled at approximately 65 sites in the U.S. Read more about this study

Who is it for?
Ages 2 to 60 years
Conditions the study is for
Epilepsy, Epilepsy, Generalized, Seizures
What is being tested?
Clobazam Low Dose, Clobazam Medium Dose and Clobazam High Dose
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
238 participants
Where
53 sitesin 5 countries
Study dates
Aug 2007to Apr 2010
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

  • Patient must have been <11 years of age at the onset of LGS.
  • Patient must have LGS.
  • Patient must be on at least 1 AED.
  • Parent or caregiver must be able to keep an accurate seizure diary.

Who cannot join

  • 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.
  • Patient has had an episode of status epilepticus within 12 weeks of baseline.
  • Patient has had an anoxic episode requiring resuscitation within 6 months of screening.
  • Patient has a clinically significant history of an allergic reaction or significant sensitivity to benzodiazepines.
  • Patient is taking more than 3 concurrent AEDs.
  • Patient has been on the ketogenic diet for less than 30 days prior to screening or suffers from frequent stooling.
Show all 11Show fewer
  • If the patient has a Vagal Nerve Stimulator (VNS), the settings have not been stable for at least 30 days prior to screening.
  • Patient has taken corticotropins in the 6 months prior to screening.
  • Patient is currently taking long-term systemic steroids (excluding inhaled mediation 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 patient is taking felbamate, has been taking it for less than 1 year prior to screening.
  • Other protocol-defined inclusion and exclusion criteria may apply.

Trial locations and contacts

53 sites in 5 countries.

53 sites in 5 countries

United States34 sites

  • Medical College of Georgia

    Augusta, Georgia, 30912

  • The Children's Hospital

    Aurora, Colorado, 80045

  • Mid-Atlantic Epilepsy and Sleep Center

    Bethesda, Maryland, 20817

  • Pediatric Neurology of Idaho Children's Specialty Center

    Boise, Idaho, 83712

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • The Comprehensive Epilepsy Care Center for Children and Adults

    Chesterfield, Missouri, 63017

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Children's Memorial Hospital

    Chicago, Illinois, 61516

  • University Neurology, Inc.

    Cincinnati, Ohio, 45219

  • Children's Medical Center at UT Southwestern-Dallas

    Dallas, Texas, 75235

  • Cook Children's Health Care System

    Fort Worth, Texas, 76104

  • Baylor College of Medicine Pediatric Neurology

    Houston, Texas, 77030

  • University of Alabama at Birmingham

    Huntsville, Alabama, 35081

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky, Kentucky Clinic, Department of Neurology

    Lexington, Kentucky, 40536-0284

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • Pediatric Neurology and Epilepsy Center

    Loxahatchee Groves, Florida, 33470

  • UTMG Pediatric Neurology

    Memphis, Tennessee, 38105

  • Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08901

  • St. Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Child Neurology Center of NW FL

    Pensacola, Florida, 32504

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Jefferson Epilepsy Center

    Philadelphia, Pennsylvania, 19107

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85216

  • Virginia Commonwealth University

    Richmond, Virginia, 23298-0211

  • University of Rochester Medical Center

    Rochester, New York, 14450

  • Minnesota Epilepsy Group

    Saint Paul, Minnesota, 55012

  • LSU Health Sciences Center

    Shreveport, Louisiana, 71103

  • University of South Florida

    Tampa, Florida, 33606

  • Pediatric Epilepsy & Neurology Specialists

    Tampa, Florida, 33609

  • Clinical Research Center of New Jersey (CRCNJ)

    Voorhees Township, New Jersey, 08043

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

India14 sites

  • Neurology Center

    Ahmedabad, Gujarat, 380006

  • St. John's Medical College Hospital

    Bangalore, Karnataka, 560034

  • Dr. Kamakshi Memorial Hospital

    Chennai, Tamil Nadu, 600 100

  • Institute of Human Behaviour and Allied Sciences

    Delhi, New Delhi, 110095

  • Deenanath Mangeshkar Hospital and Research Center

    Erandawane, Pune, 411004

  • Apollo Gleneagles Hospitals

    Kolkata, West Bengal, 700054

  • Chhatrapati Sahu Ji Maharaj Medical University

    Lucknow, Uttra Pradesh, 226 003

  • Christian Medical College

    Ludhiana, Punjab, 1410108

  • Malikatta Neuro Center

    Mangalore, Karnataka, 575002

  • K. S. Hedge Medical Academy

    Mangalore, Karnataka, 575018

  • Jaslok Hospital & Research Centre

    Mumbai, Maharashtra, 400026

  • P.D. Hinduja National Hospital Medical Research Centre

    Mumbai, Mumbai, 400016

  • Maulana Azad Medical College and Associated Lok Nayak Govind Ballabh Pant Hospitals and Guru Nanak Eye centre

    New Delhi, National Capital Territory of Delhi, 110002

  • KEM Hospital & Research Centre

    Pune, Maharashtra, 411 011

Other trials in India

Australia3 sites

  • Strategic Health Evaluators

    Chatswood, New South Wales, 2067

  • Royal Melbourne Hospital Department of Neurology

    Melbourne, Victoria, 3050

  • Austin & Repatriation Hospital (Austin Health) Epilepsy Research Centre

    Melbourne, Victoria, 3081

Other trials in Australia

Belarus1 site

  • Vitebsk Regional Diagnostic Center

    Vitebsk, 210023

Other trials in Belarus

Lithuania1 site

  • Kaunas University of Medicine Hospital

    Kaunas, LT 50009

Other trials in Lithuania

About this study

Official title: Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome

The purpose of this study is to evaluate the safety and efficacy of clobazam as adjunctive therapy in the treatment of seizures which lead to drop attacks (drop seizures) in patients 2 to 60 years of age with Lennox-Gastaut Syndrome (LGS). Patients will be enrolled at approximately 65 sites in the U.S. and ex-US for up to 23 weeks. Patients will be randomly assigned to either a low, medium or high dose, or placebo. The study will include a baseline period, a titration period and a maintenance period. After the maintenance period, patients will either continue into an open-label extension study or enter the taper period with a final visit 1 week after the last dose.

Read the detailed description

LGS poses a significant treatment challenge. No single antiepileptic drug (AED) provides satisfactory relief for all or most patients with LGS and a combination of treatments is often required. Even with combination therapy, many LGS patients show resistance to treatment. Adjunctive therapy with newer anticonvulsant medications has demonstrated efficacy for some patients, although polytherapy and high medication doses are often associated with unfavorable adverse event profiles.

More effective and better-tolerated treatment options are needed for this population of medically intractable epilepsy patients. Clobazam may provide an improved safety profile compared to other AEDs currently approved for the treatment of LGS and may have less hypotonia and drooling effects than other benzodiazepines.

Being tested
Clobazam Low Dose, Clobazam Medium Dose, Clobazam High Dose, Placebo
Keywords
Epilepsy, Lennox-Gastaut Syndrome, Drop seizures, Clobazam
Medical subject headings
Epilepsy, Epilepsy, Generalized, Seizures, Lennox Gastaut Syndrome, Syncope

What participants receive

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

  • Clobazam Low DoseDrug

    Also called Onfi™

    0.25 mg/kg/day; tablets; orally; for 15-18 weeks

  • Clobazam Medium DoseDrug

    Also called Onfi™

    0.5 mg/kg/day; tablets; orally; for 15-18 weeks

  • Clobazam High DoseDrug

    Also called Onfi™

    1.0 mg/kg/day; tablets; orally; for 15-18 weeks

  • PlaceboDrug

    tablets; orally; daily for 15-18 weeks

Study groups in NCT00518713
Study groupRoleWhat they receive
Clobazam Low DoseExperimentalNot described
Receives: Drug: Clobazam Low Dose
Clobazam Medium DoseExperimentalNot described
Receives: Drug: Clobazam Medium Dose
Clobazam High DoseExperimentalNot described
Receives: Drug: Clobazam High Dose
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

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

  1. Percent Reduction in Number of Drop Seizures (12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and 12-week maintenance period

Secondary outcomes (10)

  1. Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and the first 4 weeks of the 12-week maintenance period

  2. Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period

  3. Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and the last 4 weeks of the 12-week maintenance period

  4. Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and the 12-week maintenance period

  5. Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and the first 4 weeks of the 12-week maintenance period

  6. Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period

  7. Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).

    Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal.

    Measured: 4-week baseline period and the last 4 weeks of the 12-week maintenance period

  8. Tolerance

    Study responders who have ≥50% reduction in their drop seizure rate during the first 4 or first 8 weeks of maintenance compared to the 4 week baseline period.

    Measured: 4-week baseline period and first 4/first 8 weeks of the maintenance period

  9. Investigator Global Evaluations of the Patient's Overall Change in Symptoms.

    The physician was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life 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: Week 15

  10. 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 and overall change in seizure activity and Quality of Life 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: Week 15

Timeline

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

  1. First posted21 Aug 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionDec 2009
  4. Study completionApr 2010

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
238 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00518713
Sponsor's protocol ID
13110A
Other IDs
OV1012
Status last verified
Jan 2012
First submitted
20 Aug 2007
Last updated
9 Feb 2012
Data monitoring committee
Yes

Publications

  • Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011 Oct 11;77(15):1473-81. doi: 10.1212/WNL.0b013e318232de76. Epub 2011 Sep 28.

    PubMed 21956725

  • Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 7;4(4):CD003277. doi: 10.1002/14651858.CD003277.pub4.

    PubMed 33825230

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Clobazam Low Dose, Clobazam Medium Dose and Clobazam High Dose in people with Epilepsy and Epilepsy, Generalized, run by Lundbeck LLC at 53 sites in 5 countries.

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 4 inclusion and 11 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 9 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States, India, Australia, Belarus, Lithuania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 9 Feb 2012). 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?

Percent Reduction in Number of Drop Seizures (12-week Maintenance Period). (time frame: 4-week baseline period and 12-week maintenance period). 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 NCT00518713, 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 9 Feb 2012.

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