Lorazepam for the Treatment of Status Epilepticus or Repetitive Status Epilepticus in Japan

• ClinicalTrials.gov Identifier: NCT02239380
• Recruitment Status: Completed
• First Posted: September 12, 2014
• Results First Posted: February 18, 2019
• Last Update Posted: February 18, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 10, 2014
• First Posted Date: September 12, 2014
• Results First Submitted Date: December 18, 2017
• Results First Posted Date: February 18, 2019
• Last Update Posted Date: February 18, 2019
• Actual Study Start Date: November 2014
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2018)

Percentage of Participants Who Achieved Seizure Free Interval of At Least 30 Minutes After Initial Dose (Dose 1) of Study Drug [ Time Frame: 30 minutes post Dose 1 ]

Participants with clinical benefit were defined as participants whose initial seizure stopped within 10 minutes after initial dose (Dose 1) and who continued seizure-free for at least 30 minutes after the completion of initial dose (Dose 1).

Original Primary Outcome Measures (submitted: September 10, 2014)

Percentage of Participants With Clinical Benefit [ Time Frame: 30 minutes ]

Percent of participants whose initial seizure stopped within 10 minutes after initial dose and who continued seizure-free for at least 30 minutes after the completion of initial dose (responder rate)

Current Secondary Outcome Measures (submitted: October 11, 2018)

• Percentage of Participants Who Achieved Seizure Free Interval of At Least 30 Minutes After Any Dose of Study Drug [ Time Frame: 30 minutes post Dose 1 or 2 ]
  Percentage of participants whose initial seizure stopped within 10 minutes after the administration of study drug (either Dose 1 or 2 [in 10 to 30 minutes from the initial dose]) and who continued seizure-free for at least 30 minutes were analyzed and reported in this outcome measure.
• Percentage of Participants Who Achieved Seizure Free Interval of At Least 12 Hours After Administration (Either Initial or Any Dose) of Study Drug [ Time Frame: 12 hour post Dose 1; 12 hour post Dose 1 or 2 ]
  Percentage of participants whose seizures stopped within 10 minutes after the administration of initial dose (Dose 1) of study drug and after any study drug dose (either Dose 1 or Dose 2 [in 10 to 30 minutes from the initial dose]), who continued to be seizure-free for at least 12 hours post-dose were analyzed and reported in this outcome measure.
• Percentage of Participants Who Achieved Seizure Free Interval of At Least 24 Hours After Administration (Either Initial or Any Dose) of Study Drug [ Time Frame: 24 hour post Dose 1; 24 hour post Dose 1 or 2 ]
  Percentage of participants whose seizures stopped within 10 minutes after the administration of initial dose (Dose 1) of study drug and after any study drug dose (either Dose 1 or Dose 2 [in 10 to 30 minutes from the initial dose]), who continued to be seizure-free for at least 24 hours post-dose were analyzed and reported in this outcome measure.
• Time to Resolution of Seizures From The Administration (Either Initial or Any Dose) of Study Drug [ Time Frame: 10 minutes post Dose 1; 10 minutes post Dose 1 or 2 ]
  Time to resolution (in minutes) was defined as the duration between the administration of study drug until the seizure resolved without receiving the prohibited medications.
• Time to Relapse Following The Administration (Either Initial or Any Dose) of Study Drug [ Time Frame: 24 hour post Dose 1; 24 hour post Dose 1 or 2 ]
  Time to relapse (in minutes) was defined as duration from the time of study drug administration to the time of relapse, as determined by investigator. Participants whose seizure stops within 10 minutes without receiving the prohibited medications were analyzed in this outcome measure.
• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 7 days after last dose of study drug administration (up to 12 days) ]
  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug to the end of study (Day 12), that were absent before treatment or that worsened relative to pre-treatment state. AEs include both serious and non-serious adverse events.

Original Secondary Outcome Measures (submitted: September 10, 2014)

• Percent of participants whose initial seizure stopped within 10 minutes after the administration of study drug (either initial or second dose [in 10 to 30 minutes from the initial dose]) and who continued seizure-free for at least 30 minutes. [ Time Frame: 1 hour ]
• Percent of participants whose seizures stopped within 10 minutes after the administration of study drug (only the initial dose) and who continued seizure-free for at least 12 hours post-dose. [ Time Frame: 12 hours ]
• Percent of participants whose seizures stopped within 10 minutes after the administration of study drug (either initial or second dose [in 10 to 30 minutes from the initial dose]) and who continued seizure-free for at least 12 hours post-dose. [ Time Frame: 12 hours ]
• Percent of participants whose seizures stopped within 10 minutes after the administration of study drug (only the initial dose) and who continued seizure-free for at least 24 hours post-dose. [ Time Frame: 24 hours ]
• Percent of participants whose seizures stopped within 10 minutes after the administration of study drug (either initial or second dose [in 10 to 30 minutes from the initial dose]) and who continued seizure-free for at least 24 hours post-dose. [ Time Frame: 24 hours ]
• Time to resolution of seizures from the administration of study drug (only the initial dose). [ Time Frame: 24 hours ]
• Time to resolution of seizures from the administration of study drug (either initial or second dose). [ Time Frame: 24 hours ]
• Time to relapse from the resolution of seizures following the administration of study drug (only the initial dose, within 24 hours). [ Time Frame: 24 hours ]
• Time to relapse from the resolution of seizures following the administration of study drug (either initial or second dose, within 24 hours). [ Time Frame: 24 hours ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lorazepam for the Treatment of Status Epilepticus or Repetitive Status Epilepticus in Japan
• Official Title: A Multi-center, Open-label, Non-controlled Study To Evaluate The Efficacy And Safety Of Lorazepam Intravenously Administered In Subjects With Status Epilepticus Or Repetitive Status Epilepticus
• Brief Summary: The purpose of this study is to determine the efficacy, safety and pharmacokinetics of Lorazepam on Japanese patients with Status Epilepticus or Repetitive Status Eplilepticus.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Status Epilepticus

Intervention

Drug: Lorazepam

intravenous administration. Dosage for adult subjects (16 years aged and over): 4 mg Dosage for pediatric subjects (3 months to < 16 years): 0.05 mg/kg (but not exceeding 4 mg) Frequency: Intravenous administration of lorazepam. Subjects whose seizure does not stop or recurs within 10 minutes after the initial dose may receive the same amount of lorazepam injection no earlier than 10 minutes following the initial dose.

Also, subjects whose seizure stops within 10 minutes after the initial dose, but recurs thereafter (within 12 hours) may receive the same amount of lorazepam injection; a total of 2 doses will be permitted in this study.

Study Arms

Experimental: Lorazepam

Lorazepam intravenous formulation

Intervention: Drug: Lorazepam

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 18, 2016): 26
• Original Estimated Enrollment (submitted: September 10, 2014): 25
• Actual Study Completion Date: August 2016
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects with status epilepticus or repetitive status epilepticus / cluster seizure who have seizures that can be evaluated by investigator's visual observations based on motor symptoms or who have seizures that can be evaluated by EEG.
• Subjects with status epilepticus accompanied by generalized seizure, partial seizure or secondarily generalized seizure lasting 5 minutes or longer
• Subjects with repetitive status epilepticus / cluster seizure accompanied by not less than 3 consecutive episodes of generalized seizure, partial seizure or secondarily generalized seizure in 1 hour.
• Subjects not younger than 3 months (either gender is eligible for the study)

Exclusion Criteria:

• Subjects with known or suspected recurrent seizures due to illegal drug or alcohol withdrawal
• Subjects with known history of hypersensitivity to lorazepam or benzodiazepine
• Subjects with a known history of benzodiazepine abuse.
• Subjects currently receiving lorazepam
• Subjects with angle-closure glaucoma
• Subjects with myasthenia gravis
• Subjects with either of aspartate transaminase, alanine transaminase, total bilirubin, blood urea nitrogen, or creatinine at screening visit exceeding 2x the upper limit of normal of the institutional reference value (if the data is available)
• Subjects with white blood cell count less than 3000/mm3 or neutrophil count less than 1500/mm3 at screening visit (if the data is available)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02239380
• Other Study ID Numbers: B3541002; 2017-000125-13 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: October 2018