Trial Outcomes & Findings for A Phase III Open-Label Extension Study Of Gabapentin As Adjunctive Therapy In Japanese Pediatric Patients With Partial Seizures (NCT NCT00620555)
NCT ID: NCT00620555
Last Updated: 2021-02-03
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
65 participants
Primary outcome timeframe
up to 53 weeks
Results posted on
2021-02-03
Participant Flow
Participant milestones
| Measure |
Gabapentin
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.
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|---|---|
|
Overall Study
STARTED
|
65
|
|
Overall Study
COMPLETED
|
44
|
|
Overall Study
NOT COMPLETED
|
21
|
Reasons for withdrawal
| Measure |
Gabapentin
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.
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|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Protocol Violation
|
2
|
|
Overall Study
Lack of Efficacy
|
12
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Choice of other treatment
|
1
|
|
Overall Study
Visit failure against planned
|
1
|
Baseline Characteristics
A Phase III Open-Label Extension Study Of Gabapentin As Adjunctive Therapy In Japanese Pediatric Patients With Partial Seizures
Baseline characteristics by cohort
| Measure |
Gabapentin
n=65 Participants
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.
|
|---|---|
|
Age, Customized
3-4 years
|
8 Participants
n=5 Participants
|
|
Age, Customized
5-12 years
|
42 Participants
n=5 Participants
|
|
Age, Customized
13-16 years
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 53 weeksPopulation: Safety analysis set: All paticipants who have received at least one dose of the study drug.
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.
Outcome measures
| Measure |
Gabapentin
n=65 Participants
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.
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|---|---|
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Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Discontinuation due to treatment-related AEs
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
All-causality adverse events (AEs)
|
58 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Treatment-related AEs
|
13 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
All-causality serious AEs
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Treatment-related serious AEs
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
All-causality severe AEs
|
1 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Treatment-related severe AEs
|
0 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Discontinuation due to all-causality AEs
|
4 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Dose reduction due to all-causality AEs
|
2 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (All Causalities and Treatment-Related)
Dose reduction due to treatment-related AEs
|
2 Participants
|
SECONDARY outcome
Timeframe: Up to 52 weeksPopulation: 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.
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).
Outcome measures
| Measure |
Gabapentin
n=65 Participants
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.
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|---|---|
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Response Ratio
Week 1 to 8 (n=65)
|
-0.263 Ratio
Standard Deviation 0.3141
|
|
Response Ratio
Week 9 to 16 (n=60)
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-0.256 Ratio
Standard Deviation 0.3513
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|
Response Ratio
Week 17 to 24 (n=58)
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-0.300 Ratio
Standard Deviation 0.3671
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|
Response Ratio
Week 25 to 36 (n=54)
|
-0.280 Ratio
Standard Deviation 0.3753
|
|
Response Ratio
Week 37 to 52 (n=47)
|
-0.327 Ratio
Standard Deviation 0.3712
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SECONDARY outcome
Timeframe: Up to 52 weeksPopulation: 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.
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).
Outcome measures
| Measure |
Gabapentin
n=65 Participants
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.
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|---|---|
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Responder Rate
Week 25 to 36 (n=54)
|
40.7 Percentage of participants
Interval 27.6 to 55.0
|
|
Responder Rate
Week 37 to 52 (n=47)
|
46.8 Percentage of participants
Interval 32.1 to 61.9
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|
Responder Rate
Week 1 to 8 (n=65)
|
35.4 Percentage of participants
Interval 23.9 to 48.2
|
|
Responder Rate
Week 9 to 16 (n=60)
|
40.0 Percentage of participants
Interval 27.6 to 53.5
|
|
Responder Rate
Week 17 to 24 (n=58)
|
39.7 Percentage of participants
Interval 27.1 to 53.4
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SECONDARY outcome
Timeframe: Up to 52 weeksPopulation: 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.
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).
Outcome measures
| Measure |
Gabapentin
n=65 Participants
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.
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|---|---|
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Percent Change in Seizure Frequency
Week 1 to 8 (n=65)
|
-34.2 Percent change
Interval -100.0 to 63.1
|
|
Percent Change in Seizure Frequency
Week 25 to 36 (n=54)
|
-41.6 Percent change
Interval -100.0 to 110.7
|
|
Percent Change in Seizure Frequency
Week 37 to 52 (n=47)
|
-49.2 Percent change
Interval -100.0 to 131.7
|
|
Percent Change in Seizure Frequency
Week 9 to 16 (n=60)
|
-33.0 Percent change
Interval -100.0 to 99.8
|
|
Percent Change in Seizure Frequency
Week 17 to 24 (n=58)
|
-42.0 Percent change
Interval -100.0 to 112.5
|
Adverse Events
Gabapentin
Serious events: 2 serious events
Other events: 48 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Gabapentin
n=65 participants at risk
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.
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|---|---|
|
Respiratory, thoracic and mediastinal disorders
BRONCHOPNEUMONIA
|
1.5%
1/65 • 52 weeks
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.
|
|
Nervous system disorders
ENCEPHALOPATHY
|
1.5%
1/65 • 52 weeks
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.
|
Other adverse events
| Measure |
Gabapentin
n=65 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Dental caries
|
7.7%
5/65 • 52 weeks
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.8%
7/65 • 52 weeks
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.
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
4/65 • 52 weeks
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.
|
|
General disorders
Pyrexia
|
12.3%
8/65 • 52 weeks
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.
|
|
Infections and infestations
Bronchitis
|
6.2%
4/65 • 52 weeks
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.
|
|
Infections and infestations
Influenza
|
13.8%
9/65 • 52 weeks
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.
|
|
Infections and infestations
Nasopharyngitis
|
43.1%
28/65 • 52 weeks
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.
|
|
Infections and infestations
Pharyngitis
|
6.2%
4/65 • 52 weeks
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.
|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
4/65 • 52 weeks
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.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
6.2%
4/65 • 52 weeks
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.
|
|
Injury, poisoning and procedural complications
Fall
|
6.2%
4/65 • 52 weeks
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.
|
|
Nervous system disorders
Somnolence
|
15.4%
10/65 • 52 weeks
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.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
6.2%
4/65 • 52 weeks
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER