A Phase III Open-Label Extension 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: NCT00620555
• Collaborator: (none)
• Enrollment: 65
• Locations: 22
• Arm: 1
• Duration (Months): 31
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Examine the safety and efficacy 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: 65 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52 Weeks, Open-Label, Multicenter Study Evaluating The Efficacy And Safety Of Gabapentin As Adjunctive Therapy In Pediatric Patients Who Have Completed The 12 Weeks Treatment In Study A9451162 (NCT00603473)
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related) [up to 53 weeks]

   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.

Secondary Outcome Measures

1. Response Ratio [Up to 52 weeks]

   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).

2. Responder Rate [Up to 52 weeks]

   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).

3. Percent Change in Seizure Frequency [Up to 52 weeks]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completion of study A9451162 (NCT00603473)

Exclusion Criteria:

• Seizures related to drugs or acute medical illness

• History of any serious medical or psychiatric disorder

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	Kobe	Hyogo	Japan
4	Pfizer Investigational Site	Suma-Ku,Kobe	Hyogo	Japan
5	Pfizer Investigational Site	Kanazawa	Ishikawa	Japan
6	Pfizer Investigational Site	Zentsuuji	Kagawa	Japan
7	Pfizer Investigational Site	Yokohama	Kanagawa Pref.	Japan
8	Pfizer Investigational Site	Sendai-shi	Miyagi-ken	Japan
9	Pfizer Investigational Site	Showa-Ku	Nagoya	Japan
10	Pfizer Investigational Site	Niigata-shi	Niigata	Japan
11	Pfizer Investigational Site	Kurashiki-City	Okayama Pref.	Japan
12	Pfizer Investigational Site	Okayama-shi	Okayama	Japan
13	Pfizer Investigational Site	Izumi-shi	Osaka	Japan
14	Pfizer Investigational Site	Miyakojima-ku	Osaka	Japan
15	Pfizer Investigational Site	Suita	Osaka	Japan
16	Pfizer Investigational Site	Shizuoka-shi	Shizuoka	Japan
17	Pfizer Investigational Site	Kodaira	Tokyo	Japan
18	Pfizer Investigational Site	Setagaya-ku	Tokyo	Japan
19	Pfizer Investigational Site	Shinjuku-ku	Tokyo	Japan
20	Pfizer Investigational Site	Hiroshima		Japan
21	Pfizer Investigational Site	Saitama		Japan
22	Pfizer Investigational Site	Yamagata		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: NCT00620555
• Other Study ID Numbers: A9451165
• First Posted: Feb 21, 2008
• Last Update Posted: Feb 3, 2021
• Last Verified: Nov 1, 2011

• Additional relevant MeSH terms: Epilepsies, Partial; Gabapentin

Study Results

Participant Flow

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

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 Participants	65
Age, Customized (Number) [Number]
3-4 years	8 12.3%
5-12 years	42 64.6%
13-16 years	15 23.1%
Sex: Female, Male (Count of 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.
Measure Participants	65
All-causality adverse events (AEs)	58 89.2%
Treatment-related AEs	13 20%
All-causality serious AEs	2 3.1%
Treatment-related serious AEs	0 0%
All-causality severe AEs	1 1.5%
Treatment-related severe AEs	0 0%
Discontinuation due to all-causality AEs	4 6.2%
Discontinuation due to treatment-related AEs	2 3.1%
Dose reduction due to all-causality AEs	2 3.1%
Dose reduction due to treatment-related AEs	2 3.1%

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.
Measure Participants	65
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.
Measure Participants	65
Week 1 to 8 (n=65)	35.4 54.5%
Week 9 to 16 (n=60)	40.0 61.5%
Week 17 to 24 (n=58)	39.7 61.1%
Week 25 to 36 (n=54)	40.7 62.6%
Week 37 to 52 (n=47)	46.8 72%

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.
Measure Participants	65
Week 1 to 8 (n=65)	-34.2
Week 9 to 16 (n=60)	-33.0
Week 17 to 24 (n=58)	-42.0
Week 25 to 36 (n=54)	-41.6
Week 37 to 52 (n=47)	-49.2

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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gabapentin
	Affected / at Risk (%)	# Events
Total	2/65 (3.1%)
Nervous system disorders
ENCEPHALOPATHY	1/65 (1.5%)
Respiratory, thoracic and mediastinal disorders
BRONCHOPNEUMONIA	1/65 (1.5%)
Other (Not Including Serious) Adverse Events
	Gabapentin
	Affected / at Risk (%)	# Events
Total	48/65 (73.8%)
Gastrointestinal disorders
Dental caries	5/65 (7.7%)
Diarrhoea	7/65 (10.8%)
Vomiting	4/65 (6.2%)
General disorders
Pyrexia	8/65 (12.3%)
Infections and infestations
Bronchitis	4/65 (6.2%)
Influenza	9/65 (13.8%)
Nasopharyngitis	28/65 (43.1%)
Pharyngitis	4/65 (6.2%)
Upper respiratory tract infection	4/65 (6.2%)
Injury, poisoning and procedural complications
Arthropod bite	4/65 (6.2%)
Fall	4/65 (6.2%)
Nervous system disorders
Somnolence	10/65 (15.4%)
Skin and subcutaneous tissue disorders
Eczema	4/65 (6.2%)

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.