Safety and Efficacy of Gabapen for Pediatric (Regulatory Post Marketing Commitment Plan)

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01441401
• Collaborator: (none)
• Enrollment: 82
• Duration (Months): 33

Study Details

Study Description

Brief Summary

This investigation aims to understand the following issues in pediatric patients, as well as to assess the need of a special investigation and a post-marketing clinical study:

• The frequency of treatment related adverse events.

• The frequency of efficacy assessment.

• Treatment related unlisted adverse events in Japanese Package Insert.

• Risk factors likely to affect the frequency of treatment related adverse event.

Condition or Disease	Intervention/Treatment	Phase
Epilepsies, Partial	Drug: gabapentin

Detailed Description

All the patients whom an investigator prescribes the first gabapentin should be registered consecutively until the number of subjects reaches target number in order to extract patients enrolled into the investigation at random.

Study Design

• Study Type: Observational
• Actual Enrollment: 82 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Special Investigation Of Gabapen For Pediatric (Regulatory Post Marketing Commitment Plan)
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Gabapentin Peadiatric subjects taking Gabapen Tablets and syrup.

Drug: gabapentin; According to Japanese Package Insert: For infants and children aged 3 to 12 years, a daily dosage of 10 mg/kg of gabapentin should be administered orally in 3 divided doses on the first day of treatment, and an effective dosage of 20 mg/kg should be administered to them in 3 divided doses on day 2. From day 3 on, infants aged 3 to 4 years should be maintained on the dosage of 40 mg/kg, and children aged 5 to 12 years on the dosage of 25 to 35 mg/kg administered orally in 3 divided doses, respectively (the maximum daily dosage: 1800 mg). Though the maintenance dosage may be adjusted depending on the patient's condition, the maximum daily dosage should be 50 mg/kg. At any time point, dosage should not exceed that the dosage for adults and children aged 13 years.As for children aged 13 years or over is as same as administration for adult.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Related Adverse Events [MAX 104 weeks]

   A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Relatedness to gabapentin was assessed by the investigator and sponsor (Pfizer Japan Inc.).

2. Clinical Efficacy Rate [MAX 104 weeks]

   Clinical efficacy rate, which was defined as the percentage of participants who achieved clinical efficacy over the total number of efficacy analysis population, was presented along with the corresponding exact 2-sided 95% CI. For the basis of efficacy evaluation, frequencies of epileptic seizure were recorded during the previous 4 weeks from the treatment start date, and that from the end date of assessment period. Clinical efficacy was assessed according to the following categories: (1) effective, (2) not effective, or (3) not assessable.

Secondary Outcome Measures

1. Number of Participants With Treatment-Related Adverse Events Unexpected From Japanese Package Insert [MAX 104 weeks]

   A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Expectedness of the adverse event was determined according to the Japanese package insert. Relatedness to gabapentin was assessed by the investigator and sponsor (Pfizer Japan Inc.).

2. Number of Participants With Risk Factors for Treatment-Related Adverse Events [MAX 104 weeks]

   A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Participants with treatment-related adverse events were counted by each candidate risk factor (including gender, age, and disease eligible for the survey) to assess whether these were risk factors for the treatment-related adverse events. No inferential analyses of risk factors were performed because of a small number of the events (5 events).

3. Number of Participants Who Responded to Treatment With Gabapentin by Baseline Severity of Epileptic Seizure [MAX 104 weeks]

   Participants who responded to the treatment with gabapentin were counted by the baseline severity of epileptic seizure (mild, moderate and severe) to assess whether the baseline severity of epileptic seizure was a factor affecting the treatment efficacy.

4. Number of Participants Who Responded to Treatment With Gabapentin by Baseline Frequency of Epileptic Seizure [MAX 104 weeks]

   Participants who responded to the treatment with gabapentin were counted by the baseline frequency of epileptic seizure (<=8 versus >8 episodes/per 4 weeks) to assess whether the baseline frequency of epileptic seizure was a factor affecting the treatment efficacy.

5. Number of Participants Who Responded to Treatment With Gabapentin by Number of Concomitant Antiepileptic Drugs at Baseline [MAX 104 weeks]

   Participants who responded to the treatment with gabapentin were counted by the number of concomitant epileptic drugs at baseline across 5 categories (no drug, 1 drug, 2 drugs, 3 drugs, and 4 or more drugs) to assess whether the number of concomitant epileptic drugs at baseline was a factor affecting the treatment efficacy.

6. Number of Participants Who Responded to Treatment With Gabapentin by Treatment Period [MAX 104 weeks]

   Participants who responded to the treatment with gabapentin were counted by the treatment period (non-long term [less than 1 year] or long term [1 year or more]) to assess whether the treatment period with gabapentin was a factor affecting the treatment efficacy.

Other Outcome Measures

1. Number of Participants With Key Treatment-Related Adverse Events (Central Nervous System Depressant Actions) [MAX 104 weeks]

   Central nervous system depressant actions including somnolence and ataxia were determined as key survey items by the sponsor (Pfizer Japan Inc.). These events were defined according to MedDRA/J version 17.1 as the events classified in "psychiatric disorders" or "nervous system disorders" of the system organ classes, or those classified in "asthenia" or "gait disturbance" of the preferred terms. A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Relatedness to gabapentin was assessed by the investigator and sponsor.

2. Number of Participants With Key Treatment-Related Adverse Events (Aggressive Behaviors) [MAX 104 weeks]

   Aggressive behaviors including affect lability and hostility were determined as key survey items by the sponsor (Pfizer Japan Inc.). These events were defined as the 101 preferred terms listed by pharmaceuticals and medical devices agency and classified according to MedDRA/J version 17.1. A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Relatedness to gabapentin was assessed by the investigator and sponsor.

3. Response Ratio (R Ratio) [MAX 104 weeks]

   R Ratio was calculated by the following formula, where B represented the baseline frequency of epileptic seizures during the previous 4 weeks from the treatment start date, whereas T represented the frequency of epileptic seizures during the previous 4 weeks from the end of assessment period: R Ratio = (T - B) / (T + B). R Ratio is within the range of -1 to +1, and a negative value represents a reduction in the frequency of seizure.

4. Responder Rate [MAX 104 weeks]

   Responder rate, which was defined as the percentage of participants whose R ratio was - 0.333 or less, was presented along with the corresponding exact 2-sided 95% CI. R ratio of - 0.333 or less corresponded to the decrease of epileptic seizure frequency by 50% or more.

5. Reduction From Baseline in Epileptic Seizure Frequency [MAX 104 weeks]

   Reduction from baseline in epileptic seizure frequency was defined by the following formula, where B represented the baseline frequency of epileptic seizures during the previous 4 weeks from the treatment start date, whereas T represented the frequency of epileptic seizures during the previous 4 weeks from the end of assessment period: Reduction from baseline in epileptic seizure frequency (%) = [(T-B) / B] X 100. The median percentages were presented along with the corresponding minimum and maximum percentages.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 15 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All the pediatric subjects (aged 3-15 years) whom an investigator prescribes the first gabapentin (tablets, syrup, and switch to syrup from tablet) should be registered consecutively until the number of subjects reaches target number in order to extract patients enrolled into the investigation at random.

Exclusion Criteria:

• Patients who have been enrolled in the drug use investigation of Gabapen tablets in adults (protocol No. A9451163).

• Patients who receive Gabapen tablets or syrup before, except for switched from tablets to syrup.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT01441401
• Other Study ID Numbers: A9451175
• First Posted: Sep 27, 2011
• Last Update Posted: Feb 3, 2021
• Last Verified: Aug 1, 2016

• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Gabapentin; Epilepsies; safety
• Additional relevant MeSH terms: Epilepsy; Epilepsies, Partial; Gabapentin

Study Results

Participant Flow

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Period Title: Overall Study
STARTED	82
COMPLETED	82
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Overall Participants	82
Age, Customized (Number) [Number]
3 to 4 years	14 17.1%
5 to 12 years	54 65.9%
13 to 15 years	14 17.1%
Sex: Female, Male (Count of Participants)
Female	39 47.6%
Male	43 52.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Related Adverse Events
Description	A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Relatedness to gabapentin was assessed by the investigator and sponsor (Pfizer Japan Inc.).
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis population comprised of participants who had met the inclusion criteria and had taken gabapentin at least once.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	82
Number [Participants]	5 6.1%

2. Primary Outcome

Title	Clinical Efficacy Rate
Description	Clinical efficacy rate, which was defined as the percentage of participants who achieved clinical efficacy over the total number of efficacy analysis population, was presented along with the corresponding exact 2-sided 95% CI. For the basis of efficacy evaluation, frequencies of epileptic seizure were recorded during the previous 4 weeks from the treatment start date, and that from the end date of assessment period. Clinical efficacy was assessed according to the following categories: (1) effective, (2) not effective, or (3) not assessable.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The analysis population comprised of the participants in the efficacy analysis population from which those with data not assessable were excluded. n=number of participants with assessable data at each post-baseline time point.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	75
Week 12 (n = 73)	56.2 68.5%
Week 52 (n = 52)	57.7 70.4%
Week 104 (n = 14)	64.3 78.4%
End of assessment period (n = 66)	42.4 51.7%

3. Secondary Outcome

Title	Number of Participants With Treatment-Related Adverse Events Unexpected From Japanese Package Insert
Description	A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Expectedness of the adverse event was determined according to the Japanese package insert. Relatedness to gabapentin was assessed by the investigator and sponsor (Pfizer Japan Inc.).
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis population comprised of participants who had met the inclusion criteria and had taken gabapentin at least once.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	82
Number [Participants]	0 0%

4. Secondary Outcome

Title	Number of Participants With Risk Factors for Treatment-Related Adverse Events
Description	A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Participants with treatment-related adverse events were counted by each candidate risk factor (including gender, age, and disease eligible for the survey) to assess whether these were risk factors for the treatment-related adverse events. No inferential analyses of risk factors were performed because of a small number of the events (5 events).
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis population comprised of participants who had met the inclusion criteria and had taken gabapentin at least once. No data displayed because outcome measure has zero total participants analyzed.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	0

5. Secondary Outcome

Title	Number of Participants Who Responded to Treatment With Gabapentin by Baseline Severity of Epileptic Seizure
Description	Participants who responded to the treatment with gabapentin were counted by the baseline severity of epileptic seizure (mild, moderate and severe) to assess whether the baseline severity of epileptic seizure was a factor affecting the treatment efficacy.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The efficacy analysis population comprised of the participants who had at least one post-baseline efficacy evaluation for the clinical efficacy and seizure frequency in the safety analysis population. Participants with diseases not eligible for the survey were excluded from the efficacy analysis population.

Arm/Group Title	Mild	Moderate	Severe	Unknown
Arm/Group Description	Participants with mild epileptic seizure at baseline	Participants with moderate epileptic seizure at baseline	Participants with severe epileptic seizure at baseline	Participants with unknown severity of baseline epileptic seizure
Measure Participants	9	31	25	1
Number [Participants]	6 7.3%	15 NaN	6 NaN	1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin Tablets/Syrup, Moderate, Severe
	Comments	The factor tested was "baseline severity of epileptic seizure". The null hypothesis was that there was no association between the baseline severity of epileptic seizure (mild, moderate, and severe) and the number of participants who responded to the treatment with gabapentin.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.045
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gabapentin Tablets/Syrup, Moderate, Severe
	Comments	The factor tested was "baseline severity of epileptic seizure". The null hypothesis was that there was no ordinal trend in the number of responders to the treatment with gabapentin across the baseline severity of epileptic seizure (mild, moderate, and severe).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Cochran-Armitage (EXACT)
	Comments

6. Secondary Outcome

Title	Number of Participants Who Responded to Treatment With Gabapentin by Baseline Frequency of Epileptic Seizure
Description	Participants who responded to the treatment with gabapentin were counted by the baseline frequency of epileptic seizure (<=8 versus >8 episodes/per 4 weeks) to assess whether the baseline frequency of epileptic seizure was a factor affecting the treatment efficacy.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The efficacy analysis population comprised of the participants who had at least one post-baseline efficacy evaluation for the clinical efficacy and seizure frequency in the safety analysis population. Participants with diseases not eligible for the survey were excluded from the efficacy analysis population.

Arm/Group Title	<=8 Episodes	>8 Episodes	Unknown
Arm/Group Description	Participants with baseline episodes of epileptic seizure 8 or less	Participants with baseline episodes of epileptic seizure more than 8	Participants with unknown frequency of baseline epileptic seizure
Measure Participants	25	39	2
Number [Participants]	15 18.3%	11 NaN	2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin Tablets/Syrup, Moderate
	Comments	The factor tested was "baseline frequency of epileptic seizure". The null hypothesis was that there was no difference between the baseline frequency of epileptic seizure and the number of participants who responded to the treatment with gabapentin.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Number of Participants Who Responded to Treatment With Gabapentin by Number of Concomitant Antiepileptic Drugs at Baseline
Description	Participants who responded to the treatment with gabapentin were counted by the number of concomitant epileptic drugs at baseline across 5 categories (no drug, 1 drug, 2 drugs, 3 drugs, and 4 or more drugs) to assess whether the number of concomitant epileptic drugs at baseline was a factor affecting the treatment efficacy.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The efficacy analysis population comprised of the participants who had at least one post-baseline efficacy evaluation for the clinical efficacy and seizure frequency in the safety analysis population. Participants with diseases not eligible for the survey were excluded from the efficacy analysis population.

Arm/Group Title	No Concomitant Antiepileptic Drug	One Concomitant Antiepileptic Drug	Two Concomitant Antiepileptic Drugs	Three Concomitant Antiepileptic Drugs	Four or More Concomitant Antiepileptic Drugs
Arm/Group Description	Participants taking no concomitant antiepileptic drug at baseline	Participants taking one concomitant antiepileptic drug at baseline	Participants taking two concomitant antiepileptic drugs at baseline	Participants taking three concomitant antiepileptic drugs at baseline	Participants taking four or more concomitant antiepileptic drugs at baseline
Measure Participants	1	19	19	15	12
Number [Participants]	1 1.2%	13 NaN	7 NaN	4 NaN	3 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin Tablets/Syrup, Moderate, Severe, Unknown, Four or More Concomitant Antiepileptic Drugs
	Comments	The factor tested was "number of concomitant antiepileptic drugs at baseline". The null hypothesis was that there was no association between the number of concomitant antiepileptic drugs at baseline and the number of participants who responded to the treatment with gabapentin.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gabapentin Tablets/Syrup, Moderate, Severe, Unknown, Four or More Concomitant Antiepileptic Drugs
	Comments	The factor tested was "number of concomitant antiepileptic drugs at baseline". The null hypothesis was that there was no ordinal trend in the number of responders to the treatment with gabapentin across the increasing number of concomitant antiepileptic drugs at baseline.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Cochran-Armitage (EXACT)
	Comments

8. Secondary Outcome

Title	Number of Participants Who Responded to Treatment With Gabapentin by Treatment Period
Description	Participants who responded to the treatment with gabapentin were counted by the treatment period (non-long term [less than 1 year] or long term [1 year or more]) to assess whether the treatment period with gabapentin was a factor affecting the treatment efficacy.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The efficacy analysis population comprised of the participants who had at least one post-baseline efficacy evaluation for the clinical efficacy and seizure frequency in the safety analysis population. Participants with diseases not eligible for the survey were excluded from the efficacy analysis population.

Arm/Group Title	Non-Long Term	Long Term
Arm/Group Description	Participants who received gabapentin for less than 1 year	Participants who received gabapentin for 1 year or more
Measure Participants	19	47
Number [Participants]	2 2.4%	26 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gabapentin Tablets/Syrup, Moderate
	Comments	The factor tested was "treatment period with gabapentin". The null hypothesis was that there was no association between the treatment period with gabapentin and the number of participants who responded to the treatment with gabapentin.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments

9. Other Pre-specified Outcome

Title	Number of Participants With Key Treatment-Related Adverse Events (Central Nervous System Depressant Actions)
Description	Central nervous system depressant actions including somnolence and ataxia were determined as key survey items by the sponsor (Pfizer Japan Inc.). These events were defined according to MedDRA/J version 17.1 as the events classified in "psychiatric disorders" or "nervous system disorders" of the system organ classes, or those classified in "asthenia" or "gait disturbance" of the preferred terms. A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Relatedness to gabapentin was assessed by the investigator and sponsor.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis population comprised of participants who had met the inclusion criteria and had taken gabapentin at least once.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	82
Number [Participants]	1 1.2%

10. Other Pre-specified Outcome

Title	Number of Participants With Key Treatment-Related Adverse Events (Aggressive Behaviors)
Description	Aggressive behaviors including affect lability and hostility were determined as key survey items by the sponsor (Pfizer Japan Inc.). These events were defined as the 101 preferred terms listed by pharmaceuticals and medical devices agency and classified according to MedDRA/J version 17.1. A treatment-related adverse event was any untoward medical occurrence attributed to gabapentin in a participant who received gabapentin. Relatedness to gabapentin was assessed by the investigator and sponsor.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The safety analysis population comprised of participants who had met the inclusion criteria and had taken gabapentin at least once.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	82
Number [Participants]	1 1.2%

11. Other Pre-specified Outcome

Title	Response Ratio (R Ratio)
Description	R Ratio was calculated by the following formula, where B represented the baseline frequency of epileptic seizures during the previous 4 weeks from the treatment start date, whereas T represented the frequency of epileptic seizures during the previous 4 weeks from the end of assessment period: R Ratio = (T - B) / (T + B). R Ratio is within the range of -1 to +1, and a negative value represents a reduction in the frequency of seizure.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The analysis population comprised of the participants in the efficacy analysis population who had assessable data of the frequency of epileptic seizures at the start of gabapentin treatment and at the end of assessment period. n=number of participants with assessable data at each post-baseline time point.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	73
Week 12 (n = 72)	-0.332 (0.458)
Week 52 (n = 56)	-0.409 (0.491)
Week 104 (n = 16)	-0.456 (0.507)
End of assessment period (n = 73)	-0.369 (0.509)

12. Other Pre-specified Outcome

Title	Responder Rate
Description	Responder rate, which was defined as the percentage of participants whose R ratio was - 0.333 or less, was presented along with the corresponding exact 2-sided 95% CI. R ratio of - 0.333 or less corresponded to the decrease of epileptic seizure frequency by 50% or more.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The analysis population comprised of the participants in the efficacy analysis population who had assessable data of the frequency of epileptic seizures at the start of gabapentin treatment and at the end of assessment period. n=number of participants with assessable data at each post-baseline time point.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	73
Week 12 (n = 72)	43.1 52.6%
Week 52 (n = 56)	50.0 61%
Week 104 (n = 16)	62.5 76.2%
End of assessment period (n = 73)	49.3 60.1%

13. Other Pre-specified Outcome

Title	Reduction From Baseline in Epileptic Seizure Frequency
Description	Reduction from baseline in epileptic seizure frequency was defined by the following formula, where B represented the baseline frequency of epileptic seizures during the previous 4 weeks from the treatment start date, whereas T represented the frequency of epileptic seizures during the previous 4 weeks from the end of assessment period: Reduction from baseline in epileptic seizure frequency (%) = [(T-B) / B] X 100. The median percentages were presented along with the corresponding minimum and maximum percentages.
Time Frame	MAX 104 weeks

Outcome Measure Data

Analysis Population Description

The analysis population comprised of the participants in the efficacy analysis population who had assessable data of the frequency of epileptic seizures at the start of gabapentin treatment and at the end of assessment period. n=number of participants with assessable data at each post-baseline time point.

Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
Measure Participants	73
Week 12 (n = 72)	-25.0
Week 52 (n = 56)	-49.0
Week 104 (n = 16)	-60.0
End of assessment period (n = 73)	-47.9

Adverse Events

Adverse Event Reporting Description	The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Gabapentin Tablets/Syrup
Arm/Group Description	For participants aged 13 years or older, 600 mg in 3 divided doses (div.) was administered on day 1 and an effective dose of 1200 mg in 3 div. was administered on day 2. From day 3 on, participants were maintained on 1200 mg to 1800 mg in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum daily dose of 2400 mg). For participants aged 3 to 12 years, 10 mg/kg/day was administered orally in 3 div. on day 1 of the treatment, and an effective dose of 20 mg/kg/day was administered in 3 div. on day 2. From day 3 on, participants aged 3 to 4 years were maintained on 40 mg/kg/day in 3 div. and participants aged 5 to 12 years were maintained on 25 to 35 mg/kg/day in 3 div. The maintenance dose was adjusted according to the symptoms (up to a maximum dose of 50 mg/kg/day). At any time point, the dose was not exceeded that for participants aged 13 years or older.
All Cause Mortality
	Gabapentin Tablets/Syrup
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gabapentin Tablets/Syrup
	Affected / at Risk (%)	# Events
Total	4/82 (4.9%)
Infections and infestations
Bronchitis	2/82 (2.4%)	2
Injury, poisoning and procedural complications
Humerus fracture	1/82 (1.2%)	1
Nervous system disorders
Febrile convulsion	1/82 (1.2%)	1
Other (Not Including Serious) Adverse Events
	Gabapentin Tablets/Syrup
	Affected / at Risk (%)	# Events
Total	25/82 (30.5%)
Gastrointestinal disorders
Aphthous stomatitis	1/82 (1.2%)	1
Gastric haemorrhage	1/82 (1.2%)	1
Haemorrhoids	1/82 (1.2%)	1
Abdominal pain	1/82 (1.2%)	1
Constipation	2/82 (2.4%)	2
Vomiting	1/82 (1.2%)	1
Infections and infestations
Influenza	1/82 (1.2%)	1
Gastroenteritis	3/82 (3.7%)	3
Pharyngitis	1/82 (1.2%)	1
Bronchitis	4/82 (4.9%)	4
Herpes zoster	1/82 (1.2%)	1
Paronychia	1/82 (1.2%)	1
Nasopharyngitis	12/82 (14.6%)	12
Rhinitis	2/82 (2.4%)	2
Sinusitis	1/82 (1.2%)	1
Investigations
Hepatic enzyme increased	1/82 (1.2%)	1
Metabolism and nutrition disorders
Hyperamylasaemia	1/82 (1.2%)	1
Nervous system disorders
Convulsion	1/82 (1.2%)	1
Psychiatric disorders
Dissociative disorder	1/82 (1.2%)	1
Affect lability	1/82 (1.2%)	1
Insomnia	1/82 (1.2%)	1
Renal and urinary disorders
Urinary incontinence	1/82 (1.2%)	1
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	1/82 (1.2%)	1
Upper respiratory tract inflammation	3/82 (3.7%)	3
Skin and subcutaneous tissue disorders
Acne	1/82 (1.2%)	1
Excessive granulation tissue	1/82 (1.2%)	1
Eczema	2/82 (2.4%)	2
Rash	1/82 (1.2%)	1
Dermatitis	2/82 (2.4%)	2

Limitations/Caveats

[Not Specified]

More Information

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

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.