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

• ClinicalTrials.gov Identifier: NCT00603473
• Recruitment Status: Completed
• First Posted: January 29, 2008
• Results First Posted: February 21, 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: 92

Participant Flow

Recruitment Details	Participants were screened at 27 centers in Japan.
Pre-assignment Details	Ninety subjects were enrolled in the study. Of them, 89 received the study treatment, while 1 withdrew consent.

Arm/Group Title	Gabapentin
Arm/Group Description	The dosage of oral solution for subjects aged 3 to 12 years was calculated based on their body weight. The dose was titrated for the first 3 days of the treatment period. Subjects aged 3 to 4 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 40 mg/kg/day from Day 3. Subjects aged 5 to 12 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 25 to 35 mg/kg/day from Day 3. Subjects aged 13 to 15 years received gabapentin 600 mg/day on Day 1, 1200 mg/day on Day 2 and 1200 or 1800 mg/day from Day 3. After Day 3, the dose was adjusted if necessary within the range of maintenance doses. The maximum daily dose was 600 mg for Day 1, 1200 mg for Day 2, and 1800 mg for Day 3 and thereafter.
Period Title: Overall Study
Started	89
Completed	80
Not Completed	9
Reason Not Completed
Adverse Event	4
Lack of Efficacy	4
Protocol Violation	1

Baseline Characteristics

Arm/Group Title		Gabapentin
Arm/Group Description		The dosage of oral solution for subjects aged 3 to 12 years was calculated based on their body weight. The dose was titrated for the first 3 days of the treatment period. Subjects aged 3 to 4 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 40 mg/kg/day from Day 3. Subjects aged 5 to 12 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 25 to 35 mg/kg/day from Day 3. Subjects aged 13 to 15 years received gabapentin 600 mg/day on Day 1, 1200 mg/day on Day 2 and 1200 or 1800 mg/day from Day 3. After Day 3, the dose was adjusted if necessary within the range of maintenance doses. The maximum daily dose was 600 mg for Day 1, 1200 mg for Day 2, and 1800 mg for Day 3 and thereafter.
Overall Number of Baseline Participants		89
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Number; Unit of measure: Subjects	Number Analyzed	89 participants
>= 3 years and < 5 years		11
>= 5 years and < 13 years		63
>= 13 years and =< 15 years		15
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	89 participants
	Female	40 44.9%
	Male	49 55.1%

Outcome Measures

1. Primary Outcome

Title	Response Ratio of Gabapentin in Japanese Pediatric Patients With Partial Seizures
Description	The Response Ratio calculated by the following equation was assessed as the primary endpoint: R Ratio = (T-B) / (T+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 12-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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population: Subjects who have received the study medication for at least 28 days and in whom the number of epileptic seizures used for efficacy assessment has been counted for at least 28 days in both the baseline and treatment periods.

Arm/Group Title	Gabapentin
Arm/Group Description:	The dosage of oral solution for subjects aged 3 to 12 years was calculated based on their body weight. The dose was titrated for the first 3 days of the treatment period. Subjects aged 3 to 4 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 40 mg/kg/day from Day 3. Subjects aged 5 to 12 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 25 to 35 mg/kg/day from Day 3. Subjects aged 13 to 15 years received gabapentin 600 mg/day on Day 1, 1200 mg/day on Day 2 and 1200 or 1800 mg/day from Day 3. After Day 3, the dose was adjusted if necessary within the range of maintenance doses. The maximum daily dose was 600 mg for Day 1, 1200 mg for Day 2, and 1800 mg for Day 3 and thereafter.
Overall Number of Participants Analyzed	86
Mean (95% Confidence Interval); Unit of Measure: ratio
	-0.158; (-0.221 to -0.096)

2. Secondary Outcome

Title	Responder Rate
Description	Responder Rate was defined as the percentage of subjects with a 50% or greater reduction in the seizure frequency per 28 days for the 12-week treatment period in comparison with the frequency per 28 days for the 6-week baseline period.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population: Subjects who have received the study medication for at least 28 days and in whom the number of epileptic seizures used for efficacy assessment has been counted for at least 28 days in both the baseline and treatment periods.

Arm/Group Title	Gabapentin
Arm/Group Description:	The dosage of oral solution for subjects aged 3 to 12 years was calculated based on their body weight. The dose was titrated for the first 3 days of the treatment period. Subjects aged 3 to 4 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 40 mg/kg/day from Day 3. Subjects aged 5 to 12 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 25 to 35 mg/kg/day from Day 3. Subjects aged 13 to 15 years received gabapentin 600 mg/day on Day 1, 1200 mg/day on Day 2 and 1200 or 1800 mg/day from Day 3. After Day 3, the dose was adjusted if necessary within the range of maintenance doses. The maximum daily dose was 600 mg for Day 1, 1200 mg for Day 2, and 1800 mg for Day 3 and thereafter.
Overall Number of Participants Analyzed	86
Mean (95% Confidence Interval); Unit of Measure: Percentage of Subjects
	19.8; (12.0 to 29.8)

3. Secondary Outcome

Title	Percent Change in Seizure Frequency (PCH)
Description	PCH calculated by the following equation was assessed as secondary endpoint: PCH = 100 (T-B) / 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 12-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.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (MITT) population: Subjects who have received the study medication for at least 28 days and in whom the number of epileptic seizures used for efficacy assessment has been counted for at least 28 days in both the baseline and treatment periods.

Arm/Group Title	Gabapentin
Arm/Group Description:	The dosage of oral solution for subjects aged 3 to 12 years was calculated based on their body weight. The dose was titrated for the first 3 days of the treatment period. Subjects aged 3 to 4 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 40 mg/kg/day from Day 3. Subjects aged 5 to 12 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 25 to 35 mg/kg/day from Day 3. Subjects aged 13 to 15 years received gabapentin 600 mg/day on Day 1, 1200 mg/day on Day 2 and 1200 or 1800 mg/day from Day 3. After Day 3, the dose was adjusted if necessary within the range of maintenance doses. The maximum daily dose was 600 mg for Day 1, 1200 mg for Day 2, and 1800 mg for Day 3 and thereafter.
Overall Number of Participants Analyzed	86
Median (Full Range); Unit of Measure: Percent Change
	-24.4; (-100.0 to 192.9)

Adverse Events

Time Frame	12-week treatment period, and 1-week follow-up period
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	The dosage of oral solution for subjects aged 3 to 12 years was calculated based on their body weight. The dose was titrated for the first 3 days of the treatment period. Subjects aged 3 to 4 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 40 mg/kg/day from Day 3. Subjects aged 5 to 12 years received gabapentin 10 mg/kg/day on Day 1, 20 mg/kg/day on Day 2 and 25 to 35 mg/kg/day from Day 3. Subjects aged 13 to 15 years received gabapentin 600 mg/day on Day 1, 1200 mg/day on Day 2 and 1200 or 1800 mg/day from Day 3. After Day 3, the dose was adjusted if necessary within the range of maintenance doses. The maximum daily dose was 600 mg for Day 1, 1200 mg for Day 2, and 1800 mg for Day 3 and thereafter.
All-Cause Mortality
	Gabapentin
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Gabapentin
	Affected / at Risk (%)
Total	1/89 (1.12%)
Infections and infestations
Pharyngitis † 1	1/89 (1.12%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	Gabapentin
	Affected / at Risk (%)
Total	73/89 (82.02%)
Eye disorders
Conjunctivitis † 1	3/89 (3.37%)
Gastrointestinal disorders
Diarrhoea † 1	6/89 (6.74%)
Nausea † 1	3/89 (3.37%)
General disorders
Pyrexia † 1	5/89 (5.62%)
Infections and infestations
Influenza † 1	9/89 (10.11%)
Nasopharyngitis † 1	24/89 (26.97%)
Pharyngitis † 1	6/89 (6.74%)
Rhinitis † 1	3/89 (3.37%)
Upper respiratory tract infection † 1	4/89 (4.49%)
Injury, poisoning and procedural complications
Contusion † 1	6/89 (6.74%)
Excoriation † 1	3/89 (3.37%)
Fall † 1	7/89 (7.87%)
Metabolism and nutrition disorders
Increased appetite † 1	3/89 (3.37%)
Nervous system disorders
Ataxia † 1	3/89 (3.37%)
Convulsion † 1	3/89 (3.37%)
Somnolence † 1	35/89 (39.33%)
Skin and subcutaneous tissue disorders
Rash † 1	5/89 (5.62%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12.1

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: NCT00603473
• Other Study ID Numbers: A9451162
• First Submitted: January 16, 2008
• First Posted: January 29, 2008
• Results First Submitted: December 6, 2010
• Results First Posted: February 21, 2011
• Last Update Posted: February 3, 2021