NCT00518713

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
238

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Aug 2007

Typical duration for phase_3

Geographic Reach
5 countries

53 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2007

Completed
19 days until next milestone

First Submitted

Initial submission to the registry

August 20, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 21, 2007

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2009

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2010

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

February 9, 2012

Completed
Last Updated

February 9, 2012

Status Verified

January 1, 2012

Enrollment Period

2.3 years

First QC Date

August 20, 2007

Results QC Date

November 7, 2011

Last Update Submit

January 6, 2012

Conditions

Keywords

EpilepsyLennox-Gastaut SyndromeDrop seizuresClobazam

Outcome Measures

Primary Outcomes (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.

    4-week baseline period and 12-week maintenance period

Secondary Outcomes (10)

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

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

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

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

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

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

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

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

  • 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).

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

  • +5 more secondary outcomes

Other Outcomes (2)

  • Percent Reduction in the Number of Non-drop Seizures.

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

  • Percent Reduction of Total (Drop and Non-Drop) Seizures.

    4-week baseline period and 12-week maintenance period

Study Arms (4)

Clobazam Low Dose

EXPERIMENTAL
Drug: Clobazam Low Dose

Clobazam Medium Dose

EXPERIMENTAL
Drug: Clobazam Medium Dose

Clobazam High Dose

EXPERIMENTAL
Drug: Clobazam High Dose

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

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

Also known as: Onfiâ„¢
Clobazam Low Dose

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

Also known as: Onfiâ„¢
Clobazam Medium Dose

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

Also known as: Onfiâ„¢
Clobazam High Dose

tablets; orally; daily for 15-18 weeks

Placebo

Eligibility Criteria

Age2 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (53)

University of Alabama at Birmingham

Huntsville, Alabama, 35081, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85216, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Pediatric Neurology and Epilepsy Center

Loxahatchee Groves, Florida, 33470, United States

Location

Child Neurology Center of NW FL

Pensacola, Florida, 32504, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Pediatric Epilepsy & Neurology Specialists

Tampa, Florida, 33609, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Pediatric Neurology of Idaho Children's Specialty Center

Boise, Idaho, 83712, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 61516, United States

Location

University of Kentucky, Kentucky Clinic, Department of Neurology

Lexington, Kentucky, 40536-0284, United States

Location

LSU Health Sciences Center

Shreveport, Louisiana, 71103, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Minnesota Epilepsy Group

Saint Paul, Minnesota, 55012, United States

Location

The Comprehensive Epilepsy Care Center for Children and Adults

Chesterfield, Missouri, 63017, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

Location

St. Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

Location

Clinical Research Center of New Jersey (CRCNJ)

Voorhees Township, New Jersey, 08043, United States

Location

University of Rochester Medical Center

Rochester, New York, 14450, United States

Location

University Neurology, Inc.

Cincinnati, Ohio, 45219, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Jefferson Epilepsy Center

Philadelphia, Pennsylvania, 19107, United States

Location

UTMG Pediatric Neurology

Memphis, Tennessee, 38105, United States

Location

Children's Medical Center at UT Southwestern-Dallas

Dallas, Texas, 75235, United States

Location

Cook Children's Health Care System

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine Pediatric Neurology

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298-0211, United States

Location

Strategic Health Evaluators

Chatswood, New South Wales, 2067, Australia

Location

Royal Melbourne Hospital Department of Neurology

Melbourne, Victoria, 3050, Australia

Location

Austin & Repatriation Hospital (Austin Health) Epilepsy Research Centre

Melbourne, Victoria, 3081, Australia

Location

Vitebsk Regional Diagnostic Center

Vitebsk, 210023, Belarus

Location

Neurology Center

Ahmedabad, Gujarat, 380006, India

Location

St. John's Medical College Hospital

Bangalore, Karnataka, 560034, India

Location

Malikatta Neuro Center

Mangalore, Karnataka, 575002, India

Location

K. S. Hedge Medical Academy

Mangalore, Karnataka, 575018, India

Location

Jaslok Hospital & Research Centre

Mumbai, Maharashtra, 400026, India

Location

KEM Hospital & Research Centre

Pune, Maharashtra, 411 011, India

Location

P.D. Hinduja National Hospital Medical Research Centre

Mumbai, Mumbai, 400016, India

Location

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, India

Location

Institute of Human Behaviour and Allied Sciences

Delhi, New Delhi, 110095, India

Location

Deenanath Mangeshkar Hospital and Research Center

Erandawane, Pune, 411004, India

Location

Christian Medical College

Ludhiana, Punjab, 1410108, India

Location

Dr. Kamakshi Memorial Hospital

Chennai, Tamil Nadu, 600 100, India

Location

Chhatrapati Sahu Ji Maharaj Medical University

Lucknow, Uttra Pradesh, 226 003, India

Location

Apollo Gleneagles Hospitals

Kolkata, West Bengal, 700054, India

Location

Kaunas University of Medicine Hospital

Kaunas, LT 50009, Lithuania

Location

Related Publications (3)

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

EpilepsyEpilepsy, GeneralizedSeizuresLennox Gastaut SyndromeSyncope

Interventions

Clobazam

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsEpileptic SyndromesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUnconsciousnessConsciousness DisordersNeurobehavioral Manifestations

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Email contact via H. Lundbeck A/S
Organization
Lundbeck LLC

Study Officials

  • Email contact via H. Lundbeck A/S

    LundbeckClinicalTrials@lundbeck.com

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 20, 2007

First Posted

August 21, 2007

Study Start

August 1, 2007

Primary Completion

December 1, 2009

Study Completion

April 1, 2010

Last Updated

February 9, 2012

Results First Posted

February 9, 2012

Record last verified: 2012-01

Locations