Clobazam in Patients With Lennox-Gastaut Syndrome

NCT ID: NCT00518713

Last Updated: 2012-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 238 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2010-04-30

Brief 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. 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.

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.

Conditions

Epilepsy; Epilepsy, Generalized; Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Clobazam Low Dose

Group Type: EXPERIMENTAL

Clobazam Low Dose

Intervention Type: DRUG

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

Clobazam Medium Dose

Group Type: EXPERIMENTAL

Clobazam Medium Dose

Intervention Type: DRUG

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

Clobazam High Dose

Group Type: EXPERIMENTAL

Clobazam High Dose

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

tablets; orally; daily for 15-18 weeks

Interventions

Clobazam Low Dose

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

Intervention Type: DRUG

Clobazam Medium Dose

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

Intervention Type: DRUG

Clobazam High Dose

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

Intervention Type: DRUG

Placebo

tablets; orally; daily for 15-18 weeks

Intervention Type: DRUG

Other Intervention Names

Onfi™; Onfi™; Onfi™

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lundbeck LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Email contact via H. Lundbeck A/S

Role: STUDY_DIRECTOR

LundbeckClinicalTrials@lundbeck.com

Locations

University of Alabama at Birmingham

Huntsville, Alabama, United States

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

Childrens Hospital Los Angeles

Los Angeles, California, United States

The Children's Hospital

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Pediatric Neurology and Epilepsy Center

Loxahatchee Groves, Florida, United States

Child Neurology Center of NW FL

Pensacola, Florida, United States

University of South Florida

Tampa, Florida, United States

Pediatric Epilepsy & Neurology Specialists

Tampa, Florida, United States

Medical College of Georgia

Augusta, Georgia, United States

Pediatric Neurology of Idaho Children's Specialty Center

Boise, Idaho, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Children's Memorial Hospital

Chicago, Illinois, United States

University of Kentucky, Kentucky Clinic, Department of Neurology

Lexington, Kentucky, United States

LSU Health Sciences Center

Shreveport, Louisiana, United States

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Minnesota Epilepsy Group

Saint Paul, Minnesota, United States

The Comprehensive Epilepsy Care Center for Children and Adults

Chesterfield, Missouri, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

St. Joseph's Regional Medical Center

Paterson, New Jersey, United States

Clinical Research Center of New Jersey (CRCNJ)

Voorhees Township, New Jersey, United States

University of Rochester Medical Center

Rochester, New York, United States

University Neurology, Inc.

Cincinnati, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Jefferson Epilepsy Center

Philadelphia, Pennsylvania, United States

UTMG Pediatric Neurology

Memphis, Tennessee, United States

Children's Medical Center at UT Southwestern-Dallas

Dallas, Texas, United States

Cook Children's Health Care System

Fort Worth, Texas, United States

Baylor College of Medicine Pediatric Neurology

Houston, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Strategic Health Evaluators

Chatswood, New South Wales, Australia

Royal Melbourne Hospital Department of Neurology

Melbourne, Victoria, Australia

Austin & Repatriation Hospital (Austin Health) Epilepsy Research Centre

Melbourne, Victoria, Australia

Vitebsk Regional Diagnostic Center

Vitebsk, , Belarus

Neurology Center

Ahmedabad, Gujarat, India

St. John's Medical College Hospital

Bangalore, Karnataka, India

Malikatta Neuro Center

Mangalore, Karnataka, India

K. S. Hedge Medical Academy

Mangalore, Karnataka, India

Jaslok Hospital & Research Centre

Mumbai, Maharashtra, India

KEM Hospital & Research Centre

Pune, Maharashtra, India

P.D. Hinduja National Hospital Medical Research Centre

Mumbai, Mumbai, India

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

New Delhi, National Capital Territory of Delhi, India

Institute of Human Behaviour and Allied Sciences

Delhi, New Delhi, India

Deenanath Mangeshkar Hospital and Research Center

Erandawane, Pune, India

Christian Medical College

Ludhiana, Punjab, India

Dr. Kamakshi Memorial Hospital

Chennai, Tamil Nadu, India

Chhatrapati Sahu Ji Maharaj Medical University

Lucknow, Uttra Pradesh, India

Apollo Gleneagles Hospitals

Kolkata, West Bengal, India

Kaunas University of Medicine Hospital

Kaunas, , Lithuania

Countries

United States; Australia; Belarus; India; Lithuania

References

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.

Reference Type: RESULT

PMID: 21956725 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33825230 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27683846 (View on PubMed)

Other Identifiers

OV1012

Identifier Type: OTHER

Identifier Source: secondary_id

13110A

Identifier Type: -

Identifier Source: org_study_id