Trial Outcomes & Findings for Lorazepam for the Treatment of Status Epilepticus or Repetitive Status Epilepticus in Japan (NCT NCT02239380)
NCT ID: NCT02239380
Last Updated: 2019-02-18
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
26 participants
Primary outcome timeframe
30 minutes post Dose 1
Results posted on
2019-02-18
Participant Flow
Participant milestones
| Measure |
Lorazepam
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Overall Study
STARTED
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26
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Overall Study
COMPLETED
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26
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lorazepam for the Treatment of Status Epilepticus or Repetitive Status Epilepticus in Japan
Baseline characteristics by cohort
| Measure |
Lorazepam
n=26 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Age, Continuous
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14.0 years
STANDARD_DEVIATION 12.9 • n=5 Participants
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Sex: Female, Male
Female
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10 Participants
n=5 Participants
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Sex: Female, Male
Male
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16 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: 30 minutes post Dose 1Population: Full analysis set (FAS) included all participants who received at least 1 dose of study drug, excluded those participants whose status epilepticus (SE) or repetitive SE/cluster seizure was determined on the electroencephalography (EEG).
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).
Outcome measures
| Measure |
Lorazepam
n=25 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Percentage of Participants Who Achieved Seizure Free Interval of At Least 30 Minutes After Initial Dose (Dose 1) of Study Drug
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48.0 percentage of participants
Interval 27.8 to 68.7
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SECONDARY outcome
Timeframe: 30 minutes post Dose 1 or 2Population: FAS included all participants who received at least 1 dose of study drug, excluded those participants whose SE or repetitive SE/cluster seizure was determined on the EEG.
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.
Outcome measures
| Measure |
Lorazepam
n=25 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Percentage of Participants Who Achieved Seizure Free Interval of At Least 30 Minutes After Any Dose of Study Drug
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64.0 percentage of participants
Interval 42.5 to 82.0
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SECONDARY outcome
Timeframe: 12 hour post Dose 1; 12 hour post Dose 1 or 2Population: FAS included all participants who received at least 1 dose of study drug, excluded those participants whose SE or repetitive SE/cluster seizure was determined on the EEG.
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.
Outcome measures
| Measure |
Lorazepam
n=25 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Percentage of Participants Who Achieved Seizure Free Interval of At Least 12 Hours After Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1
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32.0 percentage of participants
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Percentage of Participants Who Achieved Seizure Free Interval of At Least 12 Hours After Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1 or 2
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44.0 percentage of participants
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SECONDARY outcome
Timeframe: 24 hour post Dose 1; 24 hour post Dose 1 or 2Population: FAS included all participants who received at least 1 dose of study drug, excluded those participants whose SE or repetitive SE/cluster seizure was determined on the EEG.
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.
Outcome measures
| Measure |
Lorazepam
n=25 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Percentage of Participants Who Achieved Seizure Free Interval of At Least 24 Hours After Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1
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24.0 percentage of participants
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Percentage of Participants Who Achieved Seizure Free Interval of At Least 24 Hours After Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1 or 2
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32.0 percentage of participants
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SECONDARY outcome
Timeframe: 10 minutes post Dose 1; 10 minutes post Dose 1 or 2Population: FAS included all participants who received at least 1 dose of study drug, excluded those participants whose SE or repetitive SE/cluster seizure was determined on the EEG. Here, 'n' signifies those participants who were evaluable for specific category.
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.
Outcome measures
| Measure |
Lorazepam
n=25 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Time to Resolution of Seizures From The Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1
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1.0 minutes
Interval 0.0 to 10.0
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Time to Resolution of Seizures From The Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1 or 2
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1.0 minutes
Interval 0.0 to 10.0
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SECONDARY outcome
Timeframe: 24 hour post Dose 1; 24 hour post Dose 1 or 2Population: FAS included all participants who received at least 1 dose of study drug, excluded those participants whose SE or repetitive SE/cluster seizure was determined on the EEG. Here, number of participants analyzed (N) signifies those participants who were evaluable for this outcome measure.
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.
Outcome measures
| Measure |
Lorazepam
n=9 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Time to Relapse Following The Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1
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62.0 minutes
Interval 11.0 to 879.0
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Time to Relapse Following The Administration (Either Initial or Any Dose) of Study Drug
Post Dose 1 or 2
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103.0 minutes
Interval 23.0 to 1246.0
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SECONDARY outcome
Timeframe: Baseline up to 7 days after last dose of study drug administration (up to 12 days)Population: Safety analysis set included all participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Lorazepam
n=26 Participants
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
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12 participants
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Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
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1 participants
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Adverse Events
Lorazepam
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lorazepam
n=26 participants at risk
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Other adverse events
| Measure |
Lorazepam
n=26 participants at risk
Participants aged between 3 months to below 16 years received single intravenous dose (Dose 1) of 0.05 milligram per kilogram (mg/kg) of Lorazepam (up to a maximum dose of 4 mg) on Day 1. Participants aged above 16 years received single intravenous dose of 4 mg of Lorazepam. Participants whose seizures continued or recurred within 10 minutes following the initial dose, an additional dose (Dose 2) of 4 mg (for participants above 16 years of age) or 0.05 mg/kg dose (for participants between 3 months to below 16 years of age) was administered accordingly. Participants were followed up to 7 days after last dose of study drug administration.
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Gastrointestinal disorders
Vomiting
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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General disorders
Pyrexia
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Infections and infestations
Pneumonia
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Infections and infestations
Urinary tract infection
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Injury, poisoning and procedural complications
Fall
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Injury, poisoning and procedural complications
Laceration
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Investigations
Blood creatine phosphokinase increased
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Nervous system disorders
Ataxia
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Nervous system disorders
Balance disorder
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Nervous system disorders
Somnolence
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7.7%
2/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Psychiatric disorders
Insomnia
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7.7%
2/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Renal and urinary disorders
Pollakiuria
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Respiratory, thoracic and mediastinal disorders
Epistaxis
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Skin and subcutaneous tissue disorders
Erythema
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3.8%
1/26 • Baseline up to 7 days after last dose of study drug administration (up to 12 days)
The same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one event and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER