A Phase III Open-Label Extension Study Of Gabapentin As Adjunctive Therapy In Japanese Pediatric Patients With Partial Seizures

• ClinicalTrials.gov Identifier: NCT00620555
• Recruitment Status: Completed
• First Posted: February 21, 2008
• Results First Posted: December 20, 2011
• Last Update Posted: February 3, 2021
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsies, Partial
• Intervention: Drug: gabapentin
• Enrollment: 65

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Gabapentin
Arm/Group Description	Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day.
Period Title: Overall Study
Started	65
Completed	44
Not Completed	21
Reason Not Completed
Adverse Event	4
Protocol Violation	2
Lack of Efficacy	12
Withdrawal by Subject	1
Choice of other treatment	1
Visit failure against planned	1

Baseline Characteristics

Arm/Group Title		Gabapentin
Arm/Group Description		Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day.
Overall Number of Baseline Participants		65
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	65 participants
3-4 years		8
5-12 years		42
13-16 years		15
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	65 participants
	Female	27 41.5%
	Male	38 58.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Description	Any untoward medical occurrence in a participant who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events: those which occurred or worsened after baseline. Severe AEs: those which interferes significantly with participant's usual function. An AE resulting in any of the following outcomes, was considered to be a serious adverse event: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect.
Time Frame	up to 53 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set: All paticipants who have received at least one dose of the study drug.

Arm/Group Title	Gabapentin
Arm/Group Description:	Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day.
Overall Number of Participants Analyzed	65
Measure Type: Number; Unit of Measure: Participants
All-causality adverse events (AEs)	58
Treatment-related AEs	13
All-causality serious AEs	2
Treatment-related serious AEs	0
All-causality severe AEs	1
Treatment-related severe AEs	0
Discontinuation due to all-causality AEs	4
Discontinuation due to treatment-related AEs	2
Dose reduction due to all-causality AEs	2
Dose reduction due to treatment-related AEs	2

2. Secondary Outcome

Title	Response Ratio
Description	The Response Ratio calculated by the following equation : Response Ratio = (T minus B) divided by (T plus B), where T is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 52-week treatment period, and B is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 6-week baseline period of the previous study A9451162 (NCT00603473).
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT): Subjects who have received at least one dose of the study drug and in whom the number of epileptic seizures used for efficacy assessment has been counted in both the baseline and treatment periods.

n = number of participants who have total number of seizures at each assessment time point.

Arm/Group Title	Gabapentin
Arm/Group Description:	Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day.
Overall Number of Participants Analyzed	65
Mean (Standard Deviation); Unit of Measure: Ratio
Week 1 to 8 (n=65)	-0.263 (0.3141)
Week 9 to 16 (n=60)	-0.256 (0.3513)
Week 17 to 24 (n=58)	-0.300 (0.3671)
Week 25 to 36 (n=54)	-0.280 (0.3753)
Week 37 to 52 (n=47)	-0.327 (0.3712)

3. Secondary Outcome

Title	Responder Rate
Description	Responder Rate was defined as the percentage of subjects with a 50 percent or greater reduction in the seizure frequency per 28 days for the 52-week treatment period in comparison with the frequency per 28 days for the 6-week baseline period of the previous study A9451162 (NCT00603473).
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT): Subjects who have received at least one dose of the study drug and in whom the number of epileptic seizures used for efficacy assessment has been counted in both the baseline and treatment periods.

n = number of participants who have total number of seizures at each assessment time point.

Arm/Group Title	Gabapentin
Arm/Group Description:	Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day.
Overall Number of Participants Analyzed	65
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 1 to 8 (n=65)	35.4; (23.9 to 48.2)
Week 9 to 16 (n=60)	40.0; (27.6 to 53.5)
Week 17 to 24 (n=58)	39.7; (27.1 to 53.4)
Week 25 to 36 (n=54)	40.7; (27.6 to 55.0)
Week 37 to 52 (n=47)	46.8; (32.1 to 61.9)

4. Secondary Outcome

Title	Percent Change in Seizure Frequency
Description	Percent change in seizure frequency (PCH) was calculated as follows: PCH = 100*(T minus B) divided by B, where T is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 52-week treatment period, and B is seizure frequency per 28 days (i.e., the number of seizures per 28 days) calculated from the total number of seizures for the 6-week baseline period of the previous study A9451162 (NCT00603473).
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT): Subjects who have received at least one dose of the study drug and in whom the number of epileptic seizures used for efficacy assessment has been counted in both the baseline and treatment periods.

n = number of participants who have total number of seizures at each assessment time point.

Arm/Group Title	Gabapentin
Arm/Group Description:	Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day.
Overall Number of Participants Analyzed	65
Median (Full Range); Unit of Measure: Percent change
Week 1 to 8 (n=65)	-34.2; (-100.0 to 63.1)
Week 9 to 16 (n=60)	-33.0; (-100.0 to 99.8)
Week 17 to 24 (n=58)	-42.0; (-100.0 to 112.5)
Week 25 to 36 (n=54)	-41.6; (-100.0 to 110.7)
Week 37 to 52 (n=47)	-49.2; (-100.0 to 131.7)

Adverse Events

Time Frame	52 weeks
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. 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
Arm/Group Description	Pediatric participants received gabapentin three times daily for 52 weeks. Participants aged 3 to 12 years received oral solution (250 mg/5 mL) at the dose calculated based on their body weight; 40 mg/kg/day for 3 to 4 years old and 25 to 35 mg/kg/day for 5 to 12 years old but not exceeding 1800 mg per day. Participants aged 13 to 15 years received gabapentin tablet at the dose of 1200 or 1800 mg/day. The dose was adjusted within the range of maintenance doses. Gabapentin could be increased if necessary with the maximum dose of 50 mg/kg/day for participants aged 3 to 12 years; All participants could receive gabapentin tablet not exceeding 2400 mg per day.
All-Cause Mortality
	Gabapentin
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Gabapentin
	Affected / at Risk (%)
Total	2/65 (3.08%)
Nervous system disorders
ENCEPHALOPATHY † 1	1/65 (1.54%)
Respiratory, thoracic and mediastinal disorders
BRONCHOPNEUMONIA † 1	1/65 (1.54%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 13.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Gabapentin
	Affected / at Risk (%)
Total	48/65 (73.85%)
Gastrointestinal disorders
Dental caries † 1	5/65 (7.69%)
Diarrhoea † 1	7/65 (10.77%)
Vomiting † 1	4/65 (6.15%)
General disorders
Pyrexia † 1	8/65 (12.31%)
Infections and infestations
Bronchitis † 1	4/65 (6.15%)
Influenza † 1	9/65 (13.85%)
Nasopharyngitis † 1	28/65 (43.08%)
Pharyngitis † 1	4/65 (6.15%)
Upper respiratory tract infection † 1	4/65 (6.15%)
Injury, poisoning and procedural complications
Arthropod bite † 1	4/65 (6.15%)
Fall † 1	4/65 (6.15%)
Nervous system disorders
Somnolence † 1	10/65 (15.38%)
Skin and subcutaneous tissue disorders
Eczema † 1	4/65 (6.15%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 13.1

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: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

• Responsible Party: Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
• ClinicalTrials.gov Identifier: NCT00620555
• Other Study ID Numbers: A9451165
• First Submitted: February 11, 2008
• First Posted: February 21, 2008
• Results First Submitted: November 14, 2011
• Results First Posted: December 20, 2011
• Last Update Posted: February 3, 2021