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

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00603473
• Collaborator: (none)
• Enrollment: 92
• Locations: 26
• Arm: 1
• Duration (Months): 23
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Examine the efficacy, safety and pharmacokinetics of gabapentin as adjunctive therapy in Japanese pediatric patients with partial seizures

Condition or Disease	Intervention/Treatment	Phase
Epilepsies, Partial	Drug: gabapentin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study Evaluating, The Efficacy, Safety And Pharmacokinetics Of Gabapentin As Adjunctive Therapy In Pediatric Patients With Partial Seizures When Other Antiepileptics Do Not Provide Satisfactory Effects
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: gabapentin	Drug: gabapentin; Orally administered gabapentin

Outcome Measures

Primary Outcome Measures

1. Response Ratio of Gabapentin in Japanese Pediatric Patients With Partial Seizures [12 weeks]

   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.

Secondary Outcome Measures

1. Responder Rate [12 weeks]

   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.

2. Percent Change in Seizure Frequency (PCH) [12 weeks]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Japanese male or females, ages 3-15 years old at acquisition of informed consent, 15 years old or less at the baseline visit

• Seizures are classified as simple partial, complex partial or partial becoming secondarily generalized (defined according to the International League Against Epilepsy)

• Have not been able to achieve adequate seizure control with antiepileptic drugs

Exclusion Criteria:

• Seizures related to drugs or acute medical illness

• History of any serious medical or psychiatric disorder

• Diagnosis or history of a structural CNS lesion or an encephalopathy shown to be progressive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Obu-shi,Morioka-machi	Aichi	Japan
2	Pfizer Investigational Site	Jonan-ku	Fukuoka	Japan
3	Pfizer Investigational Site	Sapporo	Hokkaido	Japan
4	Pfizer Investigational Site	Kobe	Hyogo	Japan
5	Pfizer Investigational Site	Suma-Ku, Kobe	Hyogo	Japan
6	Pfizer Investigational Site	Kanazawa	Ishikawa	Japan
7	Pfizer Investigational Site	Zentsuuji	Kagawa	Japan
8	Pfizer Investigational Site	Yokohama	Kanagawa Pref.	Japan
9	Pfizer Investigational Site	Sendai-shi	Miyagi-ken	Japan
10	Pfizer Investigational Site	Showa-Ku	Nagoya	Japan
11	Pfizer Investigational Site	Niigata-shi	Niigata	Japan
12	Pfizer Investigational Site	Kurashiki-City	Okayama Pref.	Japan
13	Pfizer Investigational Site	Okayama-shi	Okayama	Japan
14	Pfizer Investigational Site	Izumi-shi	Osaka	Japan
15	Pfizer Investigational Site	Miyakojima-ku	Osaka	Japan
16	Pfizer Investigational Site	Suita	Osaka	Japan
17	Pfizer Investigational Site	Higashimatsuyama	Saitama	Japan
18	Pfizer Investigational Site	Shizuoka-shi	Shizuoka	Japan
19	Pfizer Investigational Site	Kiyose-shi	Tokyo	Japan
20	Pfizer Investigational Site	Kodaira	Tokyo	Japan
21	Pfizer Investigational Site	Setagaya-ku	Tokyo	Japan
22	Pfizer Investigational Site	Shinjuku-ku	Tokyo	Japan
23	Pfizer Investigational Site	Hiroshima		Japan
24	Pfizer Investigational Site	Saitama		Japan
25	Pfizer Investigational Site	Yamagata		Japan
26	Pfizer Investigational Site	Yamanashi		Japan

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: NCT00603473
• Other Study ID Numbers: A9451162
• First Posted: Jan 29, 2008
• Last Update Posted: Feb 3, 2021
• Last Verified: Jan 1, 2011

• Additional relevant MeSH terms: Seizures; Epilepsies, Partial; Gabapentin

Study Results

Participant Flow

Recruitment Details	Participants were screened at 27 centers in Japan.
Pre-assignment Detail	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

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 Participants	89
Age, Customized (Subjects) [Number]
>= 3 years and < 5 years	11
>= 5 years and < 13 years	63
>= 13 years and =< 15 years	15
Sex: Female, Male (Count of 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.
Measure Participants	86
Mean (95% Confidence Interval) [ratio]	-0.158

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.
Measure Participants	86
Mean (95% Confidence Interval) [Percentage of Subjects]	19.8

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.
Measure Participants	86
Median (Full Range) [Percent Change]	-24.4

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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gabapentin
	Affected / at Risk (%)	# Events
Total	1/89 (1.1%)
Infections and infestations
Pharyngitis	1/89 (1.1%)
Other (Not Including Serious) Adverse Events
	Gabapentin
	Affected / at Risk (%)	# Events
Total	73/89 (82%)
Eye disorders
Conjunctivitis	3/89 (3.4%)
Gastrointestinal disorders
Diarrhoea	6/89 (6.7%)
Nausea	3/89 (3.4%)
General disorders
Pyrexia	5/89 (5.6%)
Infections and infestations
Influenza	9/89 (10.1%)
Nasopharyngitis	24/89 (27%)
Pharyngitis	6/89 (6.7%)
Rhinitis	3/89 (3.4%)
Upper respiratory tract infection	4/89 (4.5%)
Injury, poisoning and procedural complications
Contusion	6/89 (6.7%)
Excoriation	3/89 (3.4%)
Fall	7/89 (7.9%)
Metabolism and nutrition disorders
Increased appetite	3/89 (3.4%)
Nervous system disorders
Ataxia	3/89 (3.4%)
Convulsion	3/89 (3.4%)
Somnolence	35/89 (39.3%)
Skin and subcutaneous tissue disorders
Rash	5/89 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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.