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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: August 17, 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

  Show 86 Study Locations
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: August 17, 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
Epilepsies, Partial
Epilepsy, Complex Partial
Epilepsy, Generalized
Seizures
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 September 23, 2016