Trial Outcomes & Findings for Valproate Dose Reduction and Its Clinical Evaluation by Introducing Lamotrigine in Japanese Women With Epilepsy - Single Arm, Multicenter, and Open-label Study (NCT NCT02100644)
NCT ID: NCT02100644
Last Updated: 2017-11-17
Results Overview
The VPA dose reduction from Baseline is defined as post VPA dose minus the Baseline VPA dose \< 0. Baseline VPA dose is the dose at the Baseline visit (Week 0) and the post VPA dose is the last VPA dose during the LTG and VPA Maintenance Phase. Percentage of participants with dose reduction during the LTG and VPA Maintenance Phase is presented.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
33 participants
Primary outcome timeframe
Baseline and at the end of the LTG and VPA Maintenance Phase, 24-46 weeks that can be varied by durations of the LTG Escalation Phase and VPA Reduction Phase
Results posted on
2017-11-17
Participant Flow
Participants (par.) receiving monotherapy treatment with sodium valproate (VPA) maintenance dose of 400-1200 milligrams/day \[mg/d\]) due to a history of partial seizures (including secondary generalized seizures) or tonic-clonic seizures, and whose seizures had been controlled for 12 weeks (wk) prior to start of treatment were enrolled in the study.
A total of 33 participants were enrolled into the study and 20 participants completed the study.
Participant milestones
| Measure |
Escalation Phase: LTG Plus VPA
Participants received a fixed maintenance dose of VPA (400-1200 mg/d) along with lamotrigine (LTG) which was gradually escalated to 200 mg/d in accordance with the information of package insert: i.e. 25 mg of LTG was orally administered once every other day for the first 2 weeks and then once daily for the following 2 weeks. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 weeks for once or twice daily administration. If there were safety concerns, the LTG dose was decreased to 100 mg/d at the discretion of the investigator or sub-investigator. If there were still safety concerns despite the dose reduction to 100 mg/d, LTG was discontinued. The total duration of this phase was 8 to18 weeks.
|
Reduction Phase: LTG Plus VPA
Participants received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was determined at the discretion of the investigator or sub-investigator: e.g., 1000 mg/d (2 weeks), 800 mg/d (2 weeks), 600 mg/d (2 weeks), 400 mg/d (2 weeks), 300 mg/d OR 1000 mg/d (4 weeks), 600 mg/d (4 weeks), 300 mg/d and when VPA was reduced to less than 300 mg/d, the dose was reduced to 300, 200, 100, and 0 mg/d in 100 mg decrements in steps of at least one week duration. When VPA was concomitantly used, LTG was administered twice daily with 200 mg/d as a maintenance dose. If there were safety concerns during the LTG Escalation Phase, a fixed maintenance dose of 100 to 200 mg/d of LTG was administered twice daily. When VPA was withdrawn (that is, VPA was reduced to 0 mg/d), LTG was required to be increased by 50-100 mg/d. If there were any safety concern, 25 mg increment was also available. The total duration of this phase was 4 to16 weeks.
|
Maintenance Phase: LTG Plus VPA
Participants received two different treatments. In one group, participants received a fixed maintenance dose of LTG 200 mg/d (or 100 to 200 mg/d if there were safety concerns during the LTG Escalation Phase) and VPA 100 mg/d (or higher if seizures occurred during the VPA Reduction Phase) were administered twice and 1-3 times daily, respectively, for 12 weeks. The frequency of administration was not changed. If seizures occurred, VPA dose could be increased/re-introduced. On the other group, after VPA was withdrawn, LTG dose was escalated up to 300 mg/d with 50-100 mg increment per 1-2 weeks. If there was safety concern or if remaining dose to 300 mg/d was below 50 mg, 25 mg increment was also available. If seizures occurred, LTG dose was increased up to 400 mg/d. If there was safety concern, LTG dose was decreased to 100 mg/d. If there was still safety concern at 100 mg/d, the participants were discontinued from the study. The total duration of this phase was 12 weeks.
|
|---|---|---|---|
|
LTG Escalation Phase
STARTED
|
33
|
0
|
0
|
|
LTG Escalation Phase
COMPLETED
|
20
|
0
|
0
|
|
LTG Escalation Phase
NOT COMPLETED
|
13
|
0
|
0
|
|
VPA Reduction Phase
STARTED
|
0
|
20
|
0
|
|
VPA Reduction Phase
COMPLETED
|
0
|
20
|
0
|
|
VPA Reduction Phase
NOT COMPLETED
|
0
|
0
|
0
|
|
LTG and VPA Maintenance Phase
STARTED
|
0
|
0
|
20
|
|
LTG and VPA Maintenance Phase
COMPLETED
|
0
|
0
|
20
|
|
LTG and VPA Maintenance Phase
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Escalation Phase: LTG Plus VPA
Participants received a fixed maintenance dose of VPA (400-1200 mg/d) along with lamotrigine (LTG) which was gradually escalated to 200 mg/d in accordance with the information of package insert: i.e. 25 mg of LTG was orally administered once every other day for the first 2 weeks and then once daily for the following 2 weeks. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 weeks for once or twice daily administration. If there were safety concerns, the LTG dose was decreased to 100 mg/d at the discretion of the investigator or sub-investigator. If there were still safety concerns despite the dose reduction to 100 mg/d, LTG was discontinued. The total duration of this phase was 8 to18 weeks.
|
Reduction Phase: LTG Plus VPA
Participants received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was determined at the discretion of the investigator or sub-investigator: e.g., 1000 mg/d (2 weeks), 800 mg/d (2 weeks), 600 mg/d (2 weeks), 400 mg/d (2 weeks), 300 mg/d OR 1000 mg/d (4 weeks), 600 mg/d (4 weeks), 300 mg/d and when VPA was reduced to less than 300 mg/d, the dose was reduced to 300, 200, 100, and 0 mg/d in 100 mg decrements in steps of at least one week duration. When VPA was concomitantly used, LTG was administered twice daily with 200 mg/d as a maintenance dose. If there were safety concerns during the LTG Escalation Phase, a fixed maintenance dose of 100 to 200 mg/d of LTG was administered twice daily. When VPA was withdrawn (that is, VPA was reduced to 0 mg/d), LTG was required to be increased by 50-100 mg/d. If there were any safety concern, 25 mg increment was also available. The total duration of this phase was 4 to16 weeks.
|
Maintenance Phase: LTG Plus VPA
Participants received two different treatments. In one group, participants received a fixed maintenance dose of LTG 200 mg/d (or 100 to 200 mg/d if there were safety concerns during the LTG Escalation Phase) and VPA 100 mg/d (or higher if seizures occurred during the VPA Reduction Phase) were administered twice and 1-3 times daily, respectively, for 12 weeks. The frequency of administration was not changed. If seizures occurred, VPA dose could be increased/re-introduced. On the other group, after VPA was withdrawn, LTG dose was escalated up to 300 mg/d with 50-100 mg increment per 1-2 weeks. If there was safety concern or if remaining dose to 300 mg/d was below 50 mg, 25 mg increment was also available. If seizures occurred, LTG dose was increased up to 400 mg/d. If there was safety concern, LTG dose was decreased to 100 mg/d. If there was still safety concern at 100 mg/d, the participants were discontinued from the study. The total duration of this phase was 12 weeks.
|
|---|---|---|---|
|
LTG Escalation Phase
Adverse Event
|
9
|
0
|
0
|
|
LTG Escalation Phase
Protocol-defined Stopping Criteria
|
1
|
0
|
0
|
|
LTG Escalation Phase
Withdrawal by Subject
|
3
|
0
|
0
|
Baseline Characteristics
Valproate Dose Reduction and Its Clinical Evaluation by Introducing Lamotrigine in Japanese Women With Epilepsy - Single Arm, Multicenter, and Open-label Study
Baseline characteristics by cohort
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk
|
|---|---|
|
Age, Continuous
|
25.6 Years
STANDARD_DEVIATION 7.73 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian- Japanese Heritage
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and at the end of the LTG and VPA Maintenance Phase, 24-46 weeks that can be varied by durations of the LTG Escalation Phase and VPA Reduction PhasePopulation: Full analysis set (FAS): comprised of all participants in the Safety Population who provided at least one efficacy data after the first dose of the investigational product during the LTG Escalation Phase.
The VPA dose reduction from Baseline is defined as post VPA dose minus the Baseline VPA dose \< 0. Baseline VPA dose is the dose at the Baseline visit (Week 0) and the post VPA dose is the last VPA dose during the LTG and VPA Maintenance Phase. Percentage of participants with dose reduction during the LTG and VPA Maintenance Phase is presented.
Outcome measures
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Percentage of Participants Who Achieved Reduction in Daily VPA Dose
|
60.6 Percentage of participants
Interval 42.14 to 77.09
|
PRIMARY outcome
Timeframe: Baseline and at the end of the LTG and VPA Maintenance Phase, 24-46 weeks that can be varied by durations of the LTG Escalation Phase and VPA Reduction PhasePopulation: FAS Population
Percent change in VPA dose is calculated as (pre-dose - post-dose) / pre-dose x 100. Pre-dose is the VPA dose at the Baseline visit and post-dose is the last VPA dose during the LTG and VPA Maintenance Phase.
Outcome measures
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Percent Change in the VPA Dose
|
-60.10 Percentage of reduction
Standard Deviation 49.290
|
SECONDARY outcome
Timeframe: Baseline and up to 46 weeksPopulation: FAS Population
The participants with no seizure, had no record in seizure dairy. Only those participants with more than one seizure were assessed for this Outcome Measure.
Outcome measures
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Number of Days in Total That Epileptic Seizures Occurred up to the LTG and VPA Maintenance Phase
|
2 Days
|
SECONDARY outcome
Timeframe: Baseline and up to 46 weeksPopulation: FAS Population. Only those participants available at the indicated phase were analyzed (represented by n=X in the category titles).
QOLIE-31-P is a questionnaire analyzed according to the scoring manual at Baseline, at the end of LTG/VPA Maintenance Phase and withdrawals for the participants aged 18 years and older (n=26, excluding 1 participant withdrawn due to protocol violation). Overall score was calculated as an average of sub scores that were normalized to 0 to 100. QOLIE-31-P has 7 subscale items (energy, mood, daily activities, cognition, medication effect, seizure worry and overall QOL). Higher score presents higher quality of life. Epileptic symptoms generally affect the QOL of participants, and so QOLIE-31-P is world widely used for the QOL assessment of adult participants. Baseline is defined as Day 1 (pre-dose) value. Change from Baseline is calculated as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Change From Baseline in Quality of Life in Epilepsy-31-P (QOLIE-31-P) in Participants Aged 18 Years and Older
LTG Escalation-Withdrawal, n=10
|
-7.19 Scores on a scale
Standard Deviation 7.531
|
|
Change From Baseline in Quality of Life in Epilepsy-31-P (QOLIE-31-P) in Participants Aged 18 Years and Older
LTG and VPA Maintenance-Visit 5, n=16
|
0.19 Scores on a scale
Standard Deviation 9.082
|
SECONDARY outcome
Timeframe: Baseline and up to 46 weeksPopulation: FAS Population. Only those participants available at the indicated phase were analyzed (represented by n=X in the category titles).
QOLIE-AD-48 is a questionnaire analyzed according to the scoring manual at Baseline, at the end of the LTG/VPA Maintenance Phase and withdrawals for participants aged 15-17 years (n=6). Particpants who has started by QOLIE-AD-48 were using the same questionnaire even after 18 years old. Overall score was calculated as an average of sub scores that were normalized to 0 to 100. QOLIE-AD-48 has 8 subscale items (epilepsy impact, memory/concentration, physical fuctioning, stigma, social support, school behavior, attitudes towards epilepsy and health perceptions). Higher score presents higher quality of life. Epileptic symptoms generally affect the QOL of participants, and so QOLIE-AD-48 is world widely used for the QOL assessment of non-adult participants. Baseline is defined as Day 1 (pre-dose) value. Change from Baseline is calculated as post-dose visit value minus Baseline value.
Outcome measures
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Change From Baseline in Quality of Life in Epilepsy for Adolescents (QOLIE-AD-48) in Participants Aged 15-17 Years
LTG Escalation-Withdrawal, n=2
|
-10.83 Units on a scale
Standard Deviation 11.862
|
|
Change From Baseline in Quality of Life in Epilepsy for Adolescents (QOLIE-AD-48) in Participants Aged 15-17 Years
LTG and VPA Maintenance-Visit 5, n=4
|
-2.67 Units on a scale
Standard Deviation 6.356
|
SECONDARY outcome
Timeframe: Up to 50 weeksPopulation: Enrolled Population: comprised of all participants who had a Baseline (Week 0) visit.
Following cases were considered for participants to have completed a part of or whole of the study. For whole period completion: participants who completed the last LTG and VPA Maintenance Phase visit (M5) in the LTG and VPA Maintenance Phase and follow-up examination. For LTG Escalation Phase completion: participants who reached 200 mg/d of LTG (or 100-200 mg/d of LTG if there were safety concerns) within 8-18 weeks of the phase. For VPA Reduction Phase completion: participants who completed the last fixed dose of VPA Reduction Phase visit (0 mg/d) (FR4) of the phase. For LTG and VPA Maintenance Phase completion: participants who completed M5 of the phase. Participants who met any of the withdrawal criteria after the start of investigational product were considered to have discontinued the study. Percentage of participants who completed or discontinued/withdrawn from the study is presented.
Outcome measures
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Percentage of Participants Who Completed or Discontinued From the Study
Completed
|
61 Percentage of participants
|
|
Percentage of Participants Who Completed or Discontinued From the Study
Withdrawn
|
39 Percentage of participants
|
SECONDARY outcome
Timeframe: From the start of study treatment until follow-up (up to 50 weeks)Population: Safety Population: comprised of participants who received at least one dose of the investigational product during the LTG Escalation Phase.
An AE is defined as untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect, based on medical or scientific judgement and all events of possible drug-induced liver injury.
Outcome measures
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 Participants
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation of the Investigational Product and/or Withdrawal From the Study, Drug-related AEs, Deaths and Serious Adverse Events (SAEs) Throughout the Study
Any AEs
|
30 Participants
|
|
Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation of the Investigational Product and/or Withdrawal From the Study, Drug-related AEs, Deaths and Serious Adverse Events (SAEs) Throughout the Study
Drug-related AEs
|
17 Participants
|
|
Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation of the Investigational Product and/or Withdrawal From the Study, Drug-related AEs, Deaths and Serious Adverse Events (SAEs) Throughout the Study
Any SAEs
|
4 Participants
|
|
Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation of the Investigational Product and/or Withdrawal From the Study, Drug-related AEs, Deaths and Serious Adverse Events (SAEs) Throughout the Study
AEs leading to discontinuation/withdrawal
|
9 Participants
|
|
Number of Participants With Adverse Events (AEs), AEs Leading to Discontinuation of the Investigational Product and/or Withdrawal From the Study, Drug-related AEs, Deaths and Serious Adverse Events (SAEs) Throughout the Study
AEs leading to death
|
0 Participants
|
Adverse Events
LTG Plus VPA (Phase 1, 2 and 3)
Serious events: 4 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 participants at risk
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
9.1%
3/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Histiocytic necrotising lymphadenitis
|
3.0%
1/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
Other adverse events
| Measure |
LTG Plus VPA (Phase 1, 2 and 3)
n=33 participants at risk
Par. received a fixed maintenance (maint) dose of VPA (400-1200 mg/d) along with LTG gradually escalated to 200 mg/d in accordance with the package insert information: i.e. 25 mg of LTG was orally administered once every other day for the first 2 wk and then once daily for the following 2 wk. Thereafter, LTG was gradually escalated by 25 to 50 mg every 1 to 2 wk for once or twice daily administration. Par. received a range of VPA dose reduction as follows: When VPA was reduced to 300 mg/d, the range of reduction was as follows: 1000 mg/d (2 wk), 800 mg/d (2 wk), 600 mg/d (2 wk), 400 mg/d (2 wk), 300 mg/d OR 1000 mg/d (4 wk), 600 mg/d (4 wk), 300 mg/d and when VPA was reduced to \< 300 mg/d, the dose was reduced to 300, 200, 100 and 0 mg/d in 100 mg decrements in steps of at least one wk duration. Par. received a fixed maint dose of LTG 200 mg/d and VPA 100 mg/d or a maint dose of LTG 200-400 mg/d were administered twice and 1-3 times daily for LTG and VPA, respectively, for 12 wk.
|
|---|---|
|
Infections and infestations
Nasopharyngitis
|
27.3%
9/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Infections and infestations
Gastroenteritis
|
12.1%
4/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Infections and infestations
Influenza
|
9.1%
3/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Nervous system disorders
Somnolence
|
15.2%
5/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Nervous system disorders
Dizziness
|
9.1%
3/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Nervous system disorders
Headache
|
9.1%
3/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Nervous system disorders
Tremor
|
6.1%
2/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.2%
5/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
6.1%
2/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Immune system disorders
Seasonal allergy
|
6.1%
2/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
6.1%
2/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
Psychiatric disorders
Insomnia
|
6.1%
2/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
|
General disorders
Pyrexia
|
9.1%
3/33 • Adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment and until the follow-up contact (up to 50 weeks).
AEs and SAEs were collected from participants of the safety population, comprised of all participants who received atleast one dose of the investigational product during the LTG Escalation Phase.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER