Efficacy and Safety of Diazepam in the Management of Refractory Epilepsy in Selected Patients Who Require Intermittent Medical Intervention for Acute Repetitive Seizures.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00319501
First received: April 27, 2006
Last updated: July 6, 2016
Last verified: July 2016
  Purpose
To evaluate the efficacy and safety of diazepam in the management of refractory epilepsy in selected patients who require intermittent medical intervention for the control of episodes of acute repetitive seizures. In addition, to assess the support provided by caregivers who are not themselves or not under the direct supervision of health care professionals at the time of administration.

Condition Intervention Phase
Seizures
Epilepsies, Partial
Epilepsy, Complex Partial
Epilepsy, Generalized
Epilepsy
Drug: Placebo
Drug: Vanquix Auto-Injector (Diazepam Injection)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Parallel, Placebo-controlled, Multicenter Study, With Optional Open-label Continuation, Of The Efficacy And Safety Of Vanquix(tm) Auto-injector (Diazepam Injection) For The Management Of Selected, Refractory, Patients With Epilepsy Who Require Intermittent Medical Intervention To Control Episodes Of Acute Repetitive Seizures

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Time to Next Seizure or Rescue Medication During the Double-blind Period (Kaplan-Meier 50th Percentile) [ Time Frame: From 15 minutes to 12 hours after study drug administration for an episode of ARS during the Double-blind Period ] [ Designated as safety issue: No ]
    An event was defined as an episode of or required rescue medication for an episode of acute repetitive seizures (ARS) within 15 minutes to 12 hours following study drug administration. Patients without an ARS event were censored at 12 hours. Diaries were provided; if no diary was returned, or the diary did not provide answers to questions about seizures and rescue during the 12-hour follow-up period, the patient was considered censored as of 15 minutes past the treatment time, unless another contact was documented. If seizure control following study drug administration was inadequate, diazepam rectal gel was provided as a rescue medication, given only in the first 4 hours after study drug administration and only if the caregiver was directed to do so by the Investigator or designee at the time of the ARS episode. Patients and their caregivers were trained to recognize the onset of an episode of ARS and when and how to administer study drug.

  • Percentage of Participants With an Event (Next Seizure or Rescue Medication) During the Open-label Period [ Time Frame: From 15 minutes to 12 hours after study drug administration for an episode of ARS during the Double-blind Period ] [ Designated as safety issue: No ]
    An event was defined as an episode of or required rescue medication for an episode of acute repetitive seizures (ARS) within 15 minutes to 12 hours following study drug administration. Patients without an ARS event were censored at 12 hours. Diaries were provided; if no diary was returned, or the diary did not provide answers to questions about seizures and rescue during the 12-hour follow-up period, the patient was considered censored as of 15 minutes past the treatment time, unless another contact was documented. If seizure control following study drug administration was inadequate, diazepam rectal gel was provided as a rescue medication, given only in the first 4 hours after study drug administration and only if the caregiver was directed to do so by the Investigator or designee at the time of the ARS episode. Patients and their caregivers were trained to recognize the onset of an episode of ARS and when and how to administer study drug.


Secondary Outcome Measures:
  • Number of Participants Requiring Rescue Medication During the Double-blind Period [ Time Frame: From 15 minutes to 12 hours following study drug administration for an episode of ARS during the Double-blind Period ] [ Designated as safety issue: No ]
    If seizure control following study drug administration was inadequate, diazepam rectal gel was provided as a rescue medication, given only in the first 4 hours after study drug administration and only if the caregiver was directed to do so by the Investigator or designee at the time of the acute repetitive seizure (ARS) episode. Each patient's specific criteria for seizure and an episode of ARS were determined by the Investigator. Patients and their caregivers were trained to use these criteria to recognize the onset of an episode of ARS and when and how to administer study drug. An episode of ARS was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

  • Number of Participants Requiring Emergency Department Visits During the Double-blind Period [ Time Frame: From 15 minutes to 12 hours following study drug administration for onset of an episode of ARS during the Double-blind Period ] [ Designated as safety issue: No ]
    Any use of emergency treatment (such as an emergency room visit) was recorded in the patient's diary, along with the date, time, and reason for the emergency treatment. Emergency department visits required some type of rescue action taken, other than the visit itself. An episode of acute repetitive seizures (ARS) was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

  • Number of Participants Requiring Rescue Medical Care Other Than Rescue Medication or Emergency Department Visits During the Double-blind Period [ Time Frame: From 15 minutes to 12 hours following study drug administration for an episode of ARS during the Double-blind Period ] [ Designated as safety issue: No ]
    Other rescue medical care consisted of care other than rescue medication or emergency department visits. Each patient's specific criteria for seizure and an episode of acute repetitive seizure (ARS) were determined by the Investigator. Patients and their caregivers were trained to use these criteria to recognize the onset of an episode of ARS and when and how to administer study drug. An episode of ARS was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

  • Mean Score on Caregiver Global Treatment Assessment During the Double-blind Period [ Time Frame: Assessments completed at the end of each treated episode of ARS in the Double-blind Period ] [ Designated as safety issue: No ]
    Caregiver global evaluation is based on seizure frequency, severity, and overall outcome compared with previous episodes and is rated on a 10-cm visual analogue scale, where 0=much worse and 10=much better. A higher score indicates greater improvement. An episode of acute repetitive seizures (ARS) is defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

  • Mean Score on Physician Global Treatment Assessment During the Double-blind Period [ Time Frame: At Visit 2 and subsequent visits in the Double-blind Period ] [ Designated as safety issue: No ]
    Physician global evaluation is based on seizure frequency, severity, and overall outcome compared with previous episodes. The physician global evaluation is rated on a 10-cm visual analogue scale, where 0=much worse and 10=much better. A higher score indicates greater improvement. An episode of acute repetitive seizures (ARS) was defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

  • Number of Participants Requiring Rescue Medication During the Open-label Period [ Time Frame: From 15 minutes to 12 hours after study drug administration during the Open-label Period ] [ Designated as safety issue: No ]
    Each patient's specific criteria for seizure and an episode of acute repetitive seizure (ARS) were determined by the Investigator. Patients and their caregivers were trained to use these criteria to recognize the onset of an episode of ARS and when and how to administer study drug. If seizure control following study drug administration was inadequate, diazepam rectal gel was provided as a rescue medication, given only in the first 4 hours after study drug administration and only if the caregiver was directed to do so by the Investigator or designee at the time of the ARS episode.

  • Number of Participants Requiring Emergency Department Visits During the Open-label Period [ Time Frame: From 15 minutes to 12 hours after study drug administration for onset of an episode of ARS during the Open-label Period ] [ Designated as safety issue: No ]
    Any use of emergency treatment (such as an emergency room visit) was recorded in the patient's diary, along with the date, time, and reason for the emergency treatment. Emergency department visits required some type of rescue action taken, other than the visit itself.

  • Number of Participants Requiring Rescue Medical Care Other Than Medication or Emergency Department Visits During the Open-label Period [ Time Frame: From 15 minutes to 12 hours after study drug administration for onset of an episode of ARS during the Open-label Period ] [ Designated as safety issue: No ]
    Other rescue medical care consisted of care other than rescue medication or emergency department visits. Each patient's specific criteria for seizure and an episode of acute repetitive seizure (ARS) were determined by the Investigator. Patients and their caregivers were trained to use these criteria to recognize the onset of an episode of ARS and when and how to administer study drug.

  • Mean Score on Caregiver Global Treatment Assessment During the Open-label Period [ Time Frame: Assessments completed at the end of each treated episode of ARS in the Open-label Period ] [ Designated as safety issue: No ]
    Caregiver global evaluation is based on seizure frequency, severity, and overall outcome compared with previous episodes and is rated on a 10-cm visual analogue scale, where 0=much worse and 10=much better. A higher score indicates greater improvement. An episode of acute repetitive seizures (ARS) is defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.

  • Mean Score on Physician Global Treatment Assessment During the Open-label Period [ Time Frame: From Visit 2 and subsequent visits in the Open-label Period to discharge or study termination ] [ Designated as safety issue: No ]
    Physician global evaluation is based on seizure frequency, severity, and overall outcome compared with previous episodes and is rated on a 10-cm visual analogue scale, where 0=much worse and 10=much better. A higher score indicates greater improvement. An episode of acute repetitive seizures (ARS) is defined as an episode of multiple complex, partial, or generalized seizures occurring over a brief period (minutes to 12 hours) with the patient regaining consciousness between seizures, which were readily recognizable by the patient or a trained caregiver. ARS includes seizures sometimes referred to as serial, cluster, crescendo, or stuttering prolonged.


Enrollment: 234
Study Start Date: January 2006
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
During the Double-blind Period, participants received a single, age- and weight-appropriate dose of placebo solution as a deep intramuscular injection in the mid to outer thigh. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of acute repetitive seizures (ARS).
Drug: Placebo
Intramuscular autoinjector; administered at onset of an episode
Experimental: Diazepam
During the Double-blind Period, participants received a single, age- and weight-appropriate dose of diazepam solution, ranging from 0.2 to 0.5 mg/kg, as a deep intramuscular injection in the mid to outer thigh. Additional doses were permissible during the Open-label Period. Drug was administered by a caregiver using a spring-driven, pressure-activated, prefilled autoinjector at the onset of an episode of ARS.
Drug: Vanquix Auto-Injector (Diazepam Injection)
Intramuscular autoinjector: 5, 10, 15, or 20 mg (based on participant's age and weight); administered at the onset of an episode

  Eligibility

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria

For Patient:

  • Older than 2 years of age and between 6 and 136 kg body weight
  • Recipient of clinical diagnosis of epilepsy, taking a stable antiepileptic drug regimen for at least 2 weeks, and requiring intermittent medical intervention to control episodes of acute repetitive seizures (ARS)
  • Experienced at least 2 episodes of ARS in previous year, one of which occurred in previous 6 months
  • Has episodes of ARS that include complex partial or generalized seizures
  • Has a responsible caregiver available to participate
  • Is not pregnant or lactating and is practicing an acceptable method of birth control.

For Caregiver:

  • Age of 18 years or older and has demonstrated responsibility as a caregiver through training to:

    • Recognize an episode of repetitive seizures for which the injection was intended,
    • Administer study drug
    • Count and record seizures and respiratory rate in the patient diary,
    • Monitor the patient and record observations in the patient diary for 12 hours following study drug treatment
    • Recognize the need for immediate medical attention.

Key Exclusion Criteria

For Patient:

  • Petit mal status or petit mal variant status
  • History of ARS consistently progressing to status epilepticus
  • History of failure to respond to benzodiazepine treatment
  • Hypersensitivity to diazepam
  • Acute narrow angle glaucoma
  • Alcohol and/or other substance abuse
  • Has taken another investigational drug in previous 30 days
  • Acute or progressive neurologic or severe psychiatric disease or severe mental abnormality.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319501

  Hide Study Locations
Locations
United States, Alabama
Neurology Clinic, PC
Northport, Alabama, United States, 35476
United States, Arkansas
Clinical Trials, Inc
Little Rock, Arkansas, United States, 72205
United States, California
Stein Life Child Neurology Medical Specialists Inc.
Irvine, California, United States, 92606
Collaborative NeuroScience Network, LLC
Long Beach, California, United States, 90806
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States, 92658
Brain and Spine Surgeons of Orange County
Newport Beach, California, United States, 92663
Drug Shipment
Sacramento, California, United States, 95816
Sacramento Comprehensive Epilepsy Program
Sacramento, California, United States, 95816
Sutter Cancer Center Specialty Clinic
Sacramento, California, United States, 95816
Sutter Institute for Medical Research
Sacramento, California, United States, 95816
Northern California Cardiology
Sacramento, California, United States, 95819
United States, Florida
Bradenton Research Center, Inc.
Bradenton, Florida, United States, 34205
Morton Plant Hospital Epilepsy Clinic
Clearwater, Florida, United States, 33756
Morton Plant Hospital Pharmacy
Clearwater, Florida, United States, 33756
Child Neurology Center of NorthWest Florida
Gulf Breeze, Florida, United States, 32561
NorthWest Florida Clinical Research Group, LLC
Gulf Breeze, Florida, United States, 32561
Emery Neuroscience Center
Lighthouse Point, Florida, United States, 33064
Pediatric Neurology and Epilepsy Center
Loxahatchee, Florida, United States, 33470
Miami Children's Hospital
Miami, Florida, United States, 33155
EKG only
Orlando, Florida, United States, 32806
Pediatric Neurology, PA
Orlando, Florida, United States, 32819
AMO Corp
Tallahassee, Florida, United States, 32308
Tallahassee Neurological Clinic
Tallahassee, Florida, United States, 32308
Pediatric Epilepsy & Neurology Specialists
Tampa, Florida, United States, 33609
Willsey Research Inc
Tampa, Florida, United States, 33613
United States, Georgia
Child Neurology Associates, PC
Atlanta, Georgia, United States, 30342
Savannah Neurology, PC
Savannah, Georgia, United States, 31405
United States, Idaho
Consultants in Epilepsy and Neurology, PLLC
Boise, Idaho, United States, 83702
United States, Illinois
Comer Children's Hospital
Chicago, Illinois, United States, 60637
University of Chicago Hospital Pharmacy
Chicago, Illinois, United States, 60637
University of Chicago Medical Center (UCMC) Center for Advanced Medicine (CAM)
Chicago, Illinois, United States, 60637
University of Chicago Medical Center (UCMC)
Chicago, Illinois, United States, 60637
United States, Kentucky
University Neurologists PSC Pediatric Division
Louisville, Kentucky, United States, 40202
University of Louisville Ambulatory Care Building Clinic
Louisville, Kentucky, United States, 40202
University of Louisville Clinical Trials Unit
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Lahey Clinic Medical Center
Burlington, Massachusetts, United States, 01805
United States, Minnesota
Neurology Clinic of St Cloud
St Cloud, Minnesota, United States, 56303
United States, Missouri
The Comprehensive Epilepsy Care Center For Children and Adults
Chesterfield, Missouri, United States, 63017
MRI Location
Kansas City, Missouri, United States, 64111
St Luke's Hospital Neurological Consultants
Kansas City, Missouri, United States, 64111
St Luke's Hospital
Kansas City, Missouri, United States, 64111
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Clinical Research Center of New Jersey
Gibbsboro, New Jersey, United States, 08026
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School
New Brunswick,, New Jersey, United States, 08901
University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical Group
New Brunswick, New Jersey, United States, 08901
United States, New York
Elmwood Clinic
Buffalo, New York, United States, 14207
Millard Fillmore Gates Hospital/Comprehensive Epilepsy Center
Buffalo, New York, United States, 14209
Women and Children's Hospital of Buffalo
Buffalo, New York, United States, 14222
NYU Medical Center, Comprehensive Epilepsy Center
New York, New York, United States, 10016
Strong Memorial Hospital
Rochester, New York, United States, 14642
University of Rochester, Strong Epilepsy Center
Rochester, New York, United States, 14642
United States, North Carolina
Cone Health Child Neurology
Greensboro, North Carolina, United States, 27401
Guilford Neurologic Associates
Greensboro, North Carolina, United States, 27405
Raleigh Neurology Associates, PA
Raleigh, North Carolina, United States, 27607
United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195-5102
The Cleveland Clinic Health Systems
Cleveland, Ohio, United States, 44195-5102
Ohio State University Neurology Clinic
Columbus, Ohio, United States, 43210
Ohio State University University Hospital
Columbus, Ohio, United States, 43210
Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
North Pacific Epilepsy Research/The Northrup Center
Portland, Oregon, United States, 97210
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134-1095
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134
Wellspan Neurosciences
York, Pennsylvania, United States, 17402
Apple Hill Medical Center (EKG & Lab Draw)
York, Pennsylvania, United States, 17403
United States, South Carolina
Medical University of South Carolina Hospitals and Clinics
Charleston, South Carolina, United States, 29425
Medical University of South Carolina/Department of Pharmacy Service
Charleston, South Carolina, United States, 29425
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
The Neurology and Pain Clinic
Orangeburg, South Carolina, United States, 29118
United States, Tennessee
Mid-South Physicians Group, PLLC
Germantown, Tennessee, United States, 38138
University of Tennessee Lebonheur Pediatric Specialists Inc.
Memphis, Tennessee, United States, 38103
Access Clinical Trial, Inc.
Nashville, Tennessee, United States, 37203
CMC - Physician's Park
Nashville, Tennessee, United States, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2551
Vanderbilt Epilepsy Clinic
Nashville, Tennessee, United States, 37232
Vanderbilt University Hospital Pharmacy
Nashville, Tennessee, United States, 37232
United States, Texas
Neurological Clinic of Texas, PA
Dallas, Texas, United States, 75230
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Cook Children's Physcian Network
Fort Worth, Texas, United States, 76104
Cook Children's Medical Center Office of Grants and Research
Ft Worth, Texas, United States, 76104
Alamo City Clinical Research, LLC
San Antonio, Texas, United States, 78258
United States, Virginia
Virginia Commonwealth University Health System
Richmond, Virginia, United States, 23298-0042
Virginia Commonwealth University Division of Child Neurology
Richmond, Virginia, United States, 23298-0211
Virginia Commonwealth University Ambulatory Care Center/Department of Neurology
Richmond, Virginia, United States, 23298-0599
United States, Washington
Harborview Medical Center
Seattle, Washington, United States, 98104
University of Washington Regional Epilepsy Center, Harborview Medical Center
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00319501     History of Changes
Obsolete Identifiers: NCT01079156
Other Study ID Numbers: K826-05-3001  B4511001 
Study First Received: April 27, 2006
Results First Received: July 6, 2016
Last Updated: July 6, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Acute Repetitive Seizures
ARS
Diazepam
Cluster Seizures

Additional relevant MeSH terms:
Epilepsy
Seizures
Epilepsies, Partial
Epilepsy, Complex Partial
Epilepsy, Generalized
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Diazepam
Adjuvants, Anesthesia
Anticonvulsants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hypnotics and Sedatives
Central Nervous System Depressants
Muscle Relaxants, Central
Neuromuscular Agents
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on August 30, 2016