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

Phase 3

Completed

Conditions: Seizures
Epilepsies, Partial
Epilepsy, Complex Partial
Epilepsy, Generalized
Epilepsy

Interventions: Drug: Placebo
Drug: Vanquix Auto-Injector (Diazepam Injection)

Registration Number: NCT00319501

Lead Sponsor: Pfizer

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 234

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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).
Diazepam	Vanquix Auto-Injector (Diazepam Injection)	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.

Primary Outcome Measures

Name	Time	Method
Time to Next Seizure or Rescue Medication During the Double-blind Period (Kaplan-Meier 50th Percentile)	From 15 minutes to 12 hours after study drug administration for an episode of ARS during the Double-blind Period	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	From 15 minutes to 12 hours after study drug administration for an episode of ARS during the Double-blind Period	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

Name	Time	Method
Mean Score on Caregiver Global Treatment Assessment During the Double-blind Period	Assessments completed at the end of each treated episode of ARS in the Double-blind Period	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	At Visit 2 and subsequent visits in the Double-blind Period	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 Medical Care Other Than Medication or Emergency Department Visits During the Open-label Period	From 15 minutes to 12 hours after study drug administration for onset of an episode of ARS during the Open-label Period	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	Assessments completed at the end of each treated episode of ARS in the Open-label Period	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	From Visit 2 and subsequent visits in the Open-label Period to discharge or study termination	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.
Number of Participants Requiring Rescue Medication During the Open-label Period	From 15 minutes to 12 hours after study drug administration during the Open-label Period	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	From 15 minutes to 12 hours after study drug administration for onset of an episode of ARS during the Open-label Period	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 Medication During the Double-blind Period	From 15 minutes to 12 hours following study drug administration for an episode of ARS during the Double-blind Period	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	From 15 minutes to 12 hours following study drug administration for onset of an episode of ARS during the Double-blind Period	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	From 15 minutes to 12 hours following study drug administration for an episode of ARS during the Double-blind Period	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.

Trial Locations

Locations (85): Neurology Clinic, PC
🇺🇸
Northport, Alabama, United States
Clinical Trials, Inc
🇺🇸
Little Rock, Arkansas, United States
Stein Life Child Neurology Medical Specialists Inc.
🇺🇸
Irvine, California, United States
Collaborative NeuroScience Network, LLC
🇺🇸
Long Beach, California, United States
Hoag Memorial Hospital Presbyterian
🇺🇸
Newport Beach, California, United States
Brain and Spine Surgeons of Orange County
🇺🇸
Newport Beach, California, United States
Drug Shipment
🇺🇸
Sacramento, California, United States
Sacramento Comprehensive Epilepsy Program
🇺🇸
Sacramento, California, United States
Sutter Cancer Center Specialty Clinic
🇺🇸
Sacramento, California, United States
Sutter Institute for Medical Research
🇺🇸
Sacramento, California, United States
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Neurology Clinic, PC
🇺🇸Northport, Alabama, United States