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

• Study Type: Interventional
• Study Design: Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Status Epilepticus
• Intervention: Drug: Lorazepam
• Enrollment: 26

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Lorazepam
Arm/Group Description	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.
Period Title: Overall Study
Started	26
Completed	26
Not Completed	0

Baseline Characteristics

Arm/Group Title		Lorazepam
Arm/Group Description		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.
Overall Number of Baseline Participants		26
Baseline Analysis Population Description		Safety analysis set included all participants who received at least 1 dose of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	26 participants
		14.0 (12.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Female	10 38.5%
	Male	16 61.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Lorazepam
Arm/Group Description:	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.
Overall Number of Participants Analyzed	25
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	48.0; (27.8 to 68.7)

2. Secondary Outcome

Title	Percentage of Participants Who Achieved Seizure Free Interval of At Least 30 Minutes After Any Dose of Study Drug
Description	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.
Time Frame	30 minutes post Dose 1 or 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lorazepam
Arm/Group Description:	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.
Overall Number of Participants Analyzed	25
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	64.0; (42.5 to 82.0)

3. Secondary Outcome

Title	Percentage of Participants Who Achieved Seizure Free Interval of At Least 12 Hours After Administration (Either Initial or Any Dose) of Study Drug
Description	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.
Time Frame	12 hour post Dose 1; 12 hour post Dose 1 or 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lorazepam
Arm/Group Description:	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.
Overall Number of Participants Analyzed	25
Measure Type: Number; Unit of Measure: percentage of participants
Post Dose 1	32.0
Post Dose 1 or 2	44.0

4. Secondary Outcome

Title	Percentage of Participants Who Achieved Seizure Free Interval of At Least 24 Hours After Administration (Either Initial or Any Dose) of Study Drug
Description	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 Frame	24 hour post Dose 1; 24 hour post Dose 1 or 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lorazepam
Arm/Group Description:	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.
Overall Number of Participants Analyzed	25
Measure Type: Number; Unit of Measure: percentage of participants
Post Dose 1	24.0
Post Dose 1 or 2	32.0

5. Secondary Outcome

Title	Time to Resolution of Seizures From The Administration (Either Initial or Any Dose) of Study Drug
Description	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 Frame	10 minutes post Dose 1; 10 minutes post Dose 1 or 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title		Lorazepam
Arm/Group Description:		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.
Overall Number of Participants Analyzed		25
Median (Full Range); Unit of Measure: minutes
Post Dose 1	Number Analyzed	15 participants
		1.0; (0 to 10)
Post Dose 1 or 2	Number Analyzed	17 participants
		1.0; (0 to 10)

6. Secondary Outcome

Title	Time to Relapse Following The Administration (Either Initial or Any Dose) of Study Drug
Description	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.
Time Frame	24 hour post Dose 1; 24 hour post Dose 1 or 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Lorazepam
Arm/Group Description:	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.
Overall Number of Participants Analyzed	9
Median (Full Range); Unit of Measure: minutes
Post Dose 1	62.0; (11 to 879)
Post Dose 1 or 2	103.0; (23 to 1246)

7. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	Baseline up to 7 days after last dose of study drug administration (up to 12 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Lorazepam
Arm/Group Description:	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.
Overall Number of Participants Analyzed	26
Measure Type: Number; Unit of Measure: participants
AEs	12
SAEs	1

Adverse Events

Time Frame	Baseline up to 7 days after last dose of study drug administration (up to 12 days)
Adverse Event Reporting Description	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.
Arm/Group Title	Lorazepam
Arm/Group Description	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.
All-Cause Mortality
	Lorazepam
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Lorazepam
	Affected / at Risk (%)
Total	1/26 (3.85%)
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration * 1	1/26 (3.85%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 19.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Lorazepam
	Affected / at Risk (%)
Total	12/26 (46.15%)
Gastrointestinal disorders
Vomiting * 1	1/26 (3.85%)
General disorders
Pyrexia * 1	1/26 (3.85%)
Infections and infestations
Pneumonia * 1	1/26 (3.85%)
Urinary tract infection * 1	1/26 (3.85%)
Injury, poisoning and procedural complications
Fall * 1	1/26 (3.85%)
Laceration * 1	1/26 (3.85%)
Investigations
Blood creatine phosphokinase increased * 1	1/26 (3.85%)
Nervous system disorders
Ataxia * 1	1/26 (3.85%)
Balance disorder * 1	1/26 (3.85%)
Somnolence * 1	2/26 (7.69%)
Psychiatric disorders
Insomnia * 1	2/26 (7.69%)
Renal and urinary disorders
Pollakiuria * 1	1/26 (3.85%)
Respiratory, thoracic and mediastinal disorders
Epistaxis * 1	1/26 (3.85%)
Skin and subcutaneous tissue disorders
Erythema * 1	1/26 (3.85%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 19.1

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 001-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02239380
• Other Study ID Numbers: B3541002; 2017-000125-13 ( EudraCT Number )
• First Submitted: September 10, 2014
• First Posted: September 12, 2014
• Results First Submitted: December 18, 2017
• Results First Posted: February 18, 2019
• Last Update Posted: February 18, 2019