Trial Outcomes & Findings for Lamotrigine Extended-Release In Elderly Patients With Epilepsy (NCT NCT00516139)
NCT ID: NCT00516139
Last Updated: 2017-01-18
Results Overview
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or causes its prolongation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. A complete list of all SAEs and AEs experienced in the study can be found in the SAE/AE section.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
122 participants
Primary outcome timeframe
From Baseline (Week 0) until 3 weeks after the end of treatment (Week 30 or 33)
Results posted on
2017-01-18
Participant Flow
The study consisted of 4 phases (Ph): 7-week (w) Dose-escalation Ph, 8-w Adjunctive Maintenance (AM) Ph, 13-w Adj. Optimization (AO) Ph or 13-w Conversion/Monotherapy (C/M) Ph, and a 2-5 w Taper/Follow up (T/F) Ph.
Participant milestones
| Measure |
Lamotrigine (LTG)-Extended Release (XR) Tablets
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|
|
Overall Study
STARTED
|
122
|
|
Overall Study
COMPLETED
|
84
|
|
Overall Study
NOT COMPLETED
|
38
|
Reasons for withdrawal
| Measure |
Lamotrigine (LTG)-Extended Release (XR) Tablets
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|
|
Overall Study
Adverse Event
|
27
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Withdrawal by Subject
|
8
|
|
Overall Study
Lack of Efficacy
|
1
|
Baseline Characteristics
Lamotrigine Extended-Release In Elderly Patients With Epilepsy
Baseline characteristics by cohort
| Measure |
LTG-XR Tablets
n=121 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|
|
Age, Continuous
|
72.5 Years
STANDARD_DEVIATION 5.53 • n=5 Participants
|
|
Gender
Female
|
59 Participants
n=5 Participants
|
|
Gender
Male
|
62 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian Heritage
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
105 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline (Week 0) until 3 weeks after the end of treatment (Week 30 or 33)Population: Safety Population: all participants who were enrolled and took at least one dose of study drug
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires inpatient hospitalization or causes its prolongation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. A complete list of all SAEs and AEs experienced in the study can be found in the SAE/AE section.
Outcome measures
| Measure |
LTG-XR Tablets
n=121 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event
Participants with any SAE
|
22 participants
|
—
|
—
|
|
Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event
Participants with any non-serious AE
|
112 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Dose-Escalation Phase (Week 7), Maintenance Phase (Week 15), Adjunctive Optimization Phase (Week 28), Conversion Phase (Week 20), Monotherapy Phase (Week 28), and end of treatment (Week 30 or 33)Population: Safety Population. Only those participants who had seizures at baseline were analyzed.
Partial-onset sz. have a focal site of onset; sz. activity is initially limited to 1 brain hemisphere. Partial sz. can remain simple or complex, or evolve to generalized tonic-clonic sz. Participants (par.) recorded the number of sz., by type as well as the episode duration of innumerable sz. activity), in daily diaries. If par. withdrew from study, data were averaged for the study portion the par. completed up to the time of drug discontinuation. Percent change from BL = (BL value minus study phase value divided by BL value) x 100; positive values indicate reduction from BL in sz. frequency.
Outcome measures
| Measure |
LTG-XR Tablets
n=55 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study
Dose-Escalation Phase (Week 7), n=55
|
97.8 Percent change in seizure frequency
Interval -146.3 to 100.0
|
—
|
—
|
|
Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study
Maintenance Phase (Week 15), n=43
|
100.0 Percent change in seizure frequency
Interval -162.5 to 100.0
|
—
|
—
|
|
Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study
Adjunctive Optimization Phase (Week 28), n=15
|
100.0 Percent change in seizure frequency
Interval 33.3 to 100.0
|
—
|
—
|
|
Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study
Conversion Phase (Week 20), n=24
|
100.0 Percent change in seizure frequency
Interval -44.5 to 100.0
|
—
|
—
|
|
Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study
Monotherapy Phase (Week 28), n=24
|
100.0 Percent change in seizure frequency
Interval -269.8 to 100.0
|
—
|
—
|
|
Percent Change From Baseline (BL) in Weekly Seizure (sz.) Frequency for All Partial Seizures During Each Phase of the Study
End Of Treatment (Week 30/33), n=55
|
90.4 Percent change in seizure frequency
Interval -86.7 to 100.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Dose-Escalation Phase (Week 7), Maintenance Phase (Week 15), Adjunctive Optimization (Adj O) Phase (Week 28), Conversion Phase (Week 20), Monotherapy Phase (Week 28), and end of treatment (ET, Week 30 or 33)Population: Safety Population. Only those participants who had seizures at baseline were analyzed.
Participants recorded the number of seizures, by seizure type, as well as the duration of episodes of innumerable seizure activity in their daily diaries during all phases of the study. For participants who withdrew from the study, seizure data were averaged for the portion of the study the participant completed up to the time of study drug discontinuation. Participants who experienced a change from Baseline in the weekly seizure frequency were categorized as having a \>=25%, \>=50%, \>=75%, or 100% reduction or a \>=50% increase in percent change from Baseline in weekly seizure frequency.
Outcome measures
| Measure |
LTG-XR Tablets
n=55 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Dose-Escalation (Week 7), >=25% reduction, n=55
|
49 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Dose-Escalation (Week 7), >=50% reduction, n=55
|
41 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Dose-Escalation (Week 7), >=75% reduction, n=55
|
30 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Dose-Escalation (Week 7), 100% reduction, n=55
|
27 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Dose-Escalation (Week 7), >=50% increase, n=55
|
2 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Maintenance (Week 15), >=25% reduction, n=43
|
39 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Maintenance (Week 15), >=50% reduction, n=43
|
37 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Maintenance (Week 15), >=75% reduction, n=43
|
33 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Maintenance (Week 15), 100% reduction, n=43
|
30 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Maintenance (Week 15), >=50% increase, n=43
|
2 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Adj O (Week 28), >=25% reduction, n=15
|
15 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Adj O (Week 28), >=50% reduction, n=15
|
14 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Adj O (Week 28), >=75% reduction, n=15
|
12 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Adj O (Week 28), 100% reduction, n=15
|
11 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Adj O (Week 28), >=50% increase, n=15
|
0 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Conversion (Week 20), >=25% reduction, n=24
|
23 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Conversion (Week 20), >=50% reduction, n=24
|
23 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Conversion (Week 20), >=75% reduction, n=24
|
19 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Conversion (Week 20), 100% reduction, n=24
|
17 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Conversion (Week 20), >=50% increase, n=24
|
0 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Monotherapy (Week 28), >=25% reduction, n=24
|
23 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Monotherapy (Week 28), >=50% reduction, n=24
|
20 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Monotherapy (Week 28), >=75% reduction, n=24
|
17 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Monotherapy (Week 28), 100% reduction, n=24
|
13 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
Monotherapy (Week 28), >=50% increase, n=24
|
1 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
ET (Week 30/33), >=25% reduction, n=55
|
47 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
ET (Week 30/33), >=50% reduction, n=55
|
44 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
ET (Week 30/33), >=75% reduction, n=55
|
36 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
ET (Week 30/33), 100% reduction, n=55
|
24 participants
|
—
|
—
|
|
Number of Participants With the Indicated Change From Baseline in Weekly Seizure Frequency During Each Phase of the Study
ET (Week 30/33), >=50% increase, n=55
|
1 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 30 or 33Population: Safety Population. Participants who were seizure-free at Baseline were analyzed.
Participants were considered to be seizure-free if they did not report any seizures at Baseline.
Outcome measures
| Measure |
LTG-XR Tablets
n=66 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Number of Seizure-free Participants at Baseline Who Remained Seizure-free Throughout the Entire Treatment Period
Remained Seizure-Free
|
53 participants
|
—
|
—
|
|
Number of Seizure-free Participants at Baseline Who Remained Seizure-free Throughout the Entire Treatment Period
Did Not Remain Seizure-Free
|
13 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 15 (Adjunctive Maintenance [Adj M] Phase), Week 28 (Adjunctive Optimization [Adj O] Phase), Week 28 (Monotherapy [Mono] Phase), and Week 28 (Early Withdrawal [WD])Population: Safety Population. Only those participants who had seizures at baseline were analyzed.
Investigators rated the participants' seizure severity at Weeks 15 and 28 of the study treatment by using the IGE scale, comprised of 7 categories: 3 for improvement (mild improvement, moderate improvement, and marked improvement), 3 for deterioration (marked deterioration, moderate deterioration, mild deterioration), and 1 for no change. Investigators assessed the degree of the participants' improvement or deterioration or determined whether the participants' condition had not changed compared to their Baseline condition.
Outcome measures
| Measure |
LTG-XR Tablets
n=91 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 15, Adj M Phase, Improvement, n=91
|
36 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 15, Adj M Phase, No change, n=91
|
54 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 15, Adj M Phase, Deterioration, n=91
|
1 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, Adj O Phase, Improvement, n=21
|
13 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, Adj O Phase, No change, n=21
|
7 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, Adj O Phase, Deterioration, n=21
|
1 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, Mono Phase, Improvement, n=63
|
29 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, Mono Phase, No change, n=63
|
33 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, Mono Phase, Deterioration, n=63
|
1 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, WD, Improvement, n=35
|
7 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, WD, No change, n=35
|
25 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Seizure Severity in the Indicated Categories, as Measured by the Investigator's Global Evaluation (IGE) Scale
Week 28, WD, Deterioration, n=35
|
3 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 15 (Adjunctive Maintenance [Adj M] Phase), Week 28 (Adjunctive Optimization [Adj O] Phase), Week 28 (Monotherapy [Mono] Phase), and Week 28 (Early Withdrawal [WD])Population: Safety Population. Participants with missing data were not analyzed.
Investigators rated the participants' overall clinical status at Weeks 15 and 28 of the study treatment by using the IGE scale, comprised of 7 categories: 3 for improvement (mild improvement, moderate improvement, and marked improvement), 3 for deterioration (marked deterioration, moderate deterioration, mild deterioration), and 1 for no change. Investigators assessed the degree of the participants' improvement or deterioration or determined whether the participants' condition had not changed compared to their Baseline condition.
Outcome measures
| Measure |
LTG-XR Tablets
n=91 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 15, Adj M Phase, Improvement, n=91
|
51 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 15, Adj M Phase, No change, n=91
|
29 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 15, Adj M Phase, Deterioration, n=91
|
11 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, Adj O Phase, Improvement, n=21
|
17 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, Adj O Phase, No change, n=21
|
2 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, Adj O Phase, Deterioration, n=21
|
2 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, Mono Phase, Improvement, n=63
|
43 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, Mono Phase, No change, n=63
|
14 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, Mono Phase, Deterioration, n=63
|
6 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, WD, Improvement, n=35
|
7 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, WD, No change, n=35
|
12 participants
|
—
|
—
|
|
Number of Participants With Changes From Baseline in Overall Clinical Status in the Indicated Categories, as Measured by the IGE Scale
Week 28, WD, Deterioration, n=35
|
16 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), Week 28 (WD), and Week 30/33 (End of study [EOS])Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
Change from Baseline was calculated by subtracting the values of systolic and diastolic blood pressures recorded by the investigator at the indicated time points in the study from the respective Baseline values.
Outcome measures
| Measure |
LTG-XR Tablets
n=119 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Systolic BP, Week 15, Adj M Phase, n=88
|
1.51 Millimeters of mercury
Standard Deviation 19.038
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Systolic BP, Week 28, Adj O Phase, n=21
|
-0.62 Millimeters of mercury
Standard Deviation 15.377
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Systolic BP, Week 28, Mono Phase, n=63
|
0.68 Millimeters of mercury
Standard Deviation 20.509
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Systolic BP, Week 28, WD, n=35
|
-4.00 Millimeters of mercury
Standard Deviation 15.566
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Systolic BP, Week 30/33, EOS, n=119
|
-2.19 Millimeters of mercury
Standard Deviation 15.928
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Diastolic BP, Week 15, Adj M Phase, n=88
|
-1.22 Millimeters of mercury
Standard Deviation 10.547
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Diastolic BP, Week 28, Adj O Phase, n=21
|
-1.05 Millimeters of mercury
Standard Deviation 7.214
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Diastolic BP, Week 28, Mono Phase, n=63
|
-0.08 Millimeters of mercury
Standard Deviation 10.754
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Diastolic BP, Week 28, WD, n=35
|
-2.09 Millimeters of mercury
Standard Deviation 8.763
|
—
|
—
|
|
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points in the Study
Diastolic BP, Week 30/33, EOS, n=119
|
-2.07 Millimeters of mercury
Standard Deviation 9.102
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), Week 28 (WD), and Week 30/33 (End of study [EOS])Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
Change from Baseline was calculated by subtracting the value of height measured by the investigator at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=120 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in the Height at the Indicated Time Points in the Study
Week 28, Adj O Phase, n=21
|
0.29 centimeters
Standard Deviation 2.217
|
—
|
—
|
|
Change From Baseline in the Height at the Indicated Time Points in the Study
Week 15, Adj M Phase, n=90
|
0.03 centimeters
Standard Deviation 1.302
|
—
|
—
|
|
Change From Baseline in the Height at the Indicated Time Points in the Study
Week 28, Mono Phase, n=62
|
-0.03 centimeters
Standard Deviation 1.293
|
—
|
—
|
|
Change From Baseline in the Height at the Indicated Time Points in the Study
Week 28, WD, n=36
|
-0.03 centimeters
Standard Deviation 1.028
|
—
|
—
|
|
Change From Baseline in the Height at the Indicated Time Points in the Study
Week 30/33, EOS, n=120
|
0.03 centimeters
Standard Deviation 1.417
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), Week 28 (WD), and Week 30/33 (End of study [EOS])Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
Change from Baseline was calculated by subtracting the value of weight measured by the investigator at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=119 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in the Weight at the Indicated Time Points in the Study
Week 15, Adj M Phase, n=88
|
-0.22 kilograms
Standard Deviation 3.204
|
—
|
—
|
|
Change From Baseline in the Weight at the Indicated Time Points in the Study
Week 28, Adj O Phase, n=21
|
-0.41 kilograms
Standard Deviation 2.968
|
—
|
—
|
|
Change From Baseline in the Weight at the Indicated Time Points in the Study
Week 28, Mono Phase, n=62
|
-0.48 kilograms
Standard Deviation 3.520
|
—
|
—
|
|
Change From Baseline in the Weight at the Indicated Time Points in the Study
Week 28, WD, n=36
|
-0.27 kilograms
Standard Deviation 3.735
|
—
|
—
|
|
Change From Baseline in the Weight at the Indicated Time Points in the Study
Week 30/33, EOS, n=119
|
-0.41 kilograms
Standard Deviation 3.470
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of basophil, eosinophil, hemoglobin, lymphocyte, monocyte, ANC, platelet count, and WBC count at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=89 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Basophil, Week 15, Adj M, n=85
|
0.00 Giga (10^9) cells per liter
Interval -0.03 to 0.06
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Basophil, Week 28, Adj O, n=19
|
0.00 Giga (10^9) cells per liter
Interval -0.02 to 0.02
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Basophil, Week 28, Mono, n=55
|
0.00 Giga (10^9) cells per liter
Interval -0.05 to 0.05
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Basophil, Week 28, WD, n=33
|
0.00 Giga (10^9) cells per liter
Interval -0.04 to 0.04
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Eosinophil, Week 15, Adj M, n=89
|
0.00 Giga (10^9) cells per liter
Interval -0.38 to 0.55
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Eosinophil, Week 28, Adj O, n=21
|
0.01 Giga (10^9) cells per liter
Interval -0.06 to 0.26
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Eosinophil, Week 28, Mono, n=61
|
0.01 Giga (10^9) cells per liter
Interval -0.23 to 0.54
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Eosinophil, Week 28, WD, n=33
|
-0.01 Giga (10^9) cells per liter
Interval -0.17 to 0.84
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Hemoglobin, Week 15, Adj M, n=85
|
-4.00 Giga (10^9) cells per liter
Interval -38.0 to 19.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Hemoglobin, Week 28, Adj O, n=19
|
-6.00 Giga (10^9) cells per liter
Interval -22.0 to 4.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Hemoglobin, Week 28, Mono, n=55
|
-4.00 Giga (10^9) cells per liter
Interval -25.0 to 10.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Hemoglobin, Week 28, WD, n=33
|
-2.00 Giga (10^9) cells per liter
Interval -21.0 to 31.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Lymphocytes, Week 15, Adj M, n=85
|
-0.12 Giga (10^9) cells per liter
Interval -1.55 to 1.52
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Lymphocytes, Week 28, Adj O, n=19
|
-0.05 Giga (10^9) cells per liter
Interval -0.61 to 0.4
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Lymphocytes, Week 28, Mono, n=55
|
-0.20 Giga (10^9) cells per liter
Interval -1.75 to 0.62
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Lymphocytes, Week 28, WD, n=33
|
-0.09 Giga (10^9) cells per liter
Interval -0.94 to 0.66
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Monocytes, Week 15, Adj M, n=85
|
-0.03 Giga (10^9) cells per liter
Interval -0.41 to 0.47
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Monocytes, Week 28, Adj O, n=19
|
0.00 Giga (10^9) cells per liter
Interval -0.55 to 0.26
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Monocytes, Week 28, Mono, n=55
|
-0.04 Giga (10^9) cells per liter
Interval -0.37 to 0.4
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Monocytes, Week 28, WD, n=33
|
-0.01 Giga (10^9) cells per liter
Interval -0.48 to 0.64
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Absolute Neutrophil Count, Week 15, Adj M, n=85
|
-0.23 Giga (10^9) cells per liter
Interval -3.0 to 5.04
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Absolute Neutrophil Count, Week 28, Adj O, n=19
|
0.09 Giga (10^9) cells per liter
Interval -2.17 to 3.31
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Absolute Neutrophil Count, Week 28, Mono, n=55
|
-0.17 Giga (10^9) cells per liter
Interval -3.18 to 2.71
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Absolute Neutrophil Count, Week 28, WD, n=33
|
0.17 Giga (10^9) cells per liter
Interval -1.99 to 6.47
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Platelet Count, Week 15, Adj M, n=84
|
1.50 Giga (10^9) cells per liter
Interval -91.0 to 226.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Platelet Count, Week 28, Adj O, n=19
|
3.00 Giga (10^9) cells per liter
Interval -55.0 to 216.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Platelet Count, Week 28, Mono, n=54
|
0.00 Giga (10^9) cells per liter
Interval -75.0 to 104.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
Platelet Count, Week 28, WD, n=32
|
6.50 Giga (10^9) cells per liter
Interval -80.0 to 172.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
White Blood Cell Count, Week 15, Adj M, n=85
|
-0.30 Giga (10^9) cells per liter
Interval -2.8 to 5.7
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
White Blood Cell Count, Week 28, Adj O, n=19
|
-0.20 Giga (10^9) cells per liter
Interval -2.4 to 3.2
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
White Blood Cell Count, Week 28, Mono, n=55
|
-0.60 Giga (10^9) cells per liter
Interval -3.5 to 2.0
|
—
|
—
|
|
Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points in the Study
White Blood Cell Count, Week 28, WD, n=33
|
0.30 Giga (10^9) cells per liter
Interval -2.2 to 6.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Percent change from Baseline = (value at each indicated time point in the study minus respective Baseline value divided by Baseline value) x 100.
Outcome measures
| Measure |
LTG-XR Tablets
n=89 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Basophil, Week 15, Adj M, n=89
|
0.00 Percent change in counts
Interval -0.8 to 1.0
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Basophil, Week 28, Adj O, n=21
|
0.00 Percent change in counts
Interval -0.5 to 0.5
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Basophil, Week 28, Mono, n=61
|
0.00 Percent change in counts
Interval -0.8 to 0.9
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Basophil, Week 28, WD, n=33
|
0.00 Percent change in counts
Interval -0.5 to 0.9
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Eosinophil, Week 15, Adj M, n=89
|
0.20 Percent change in counts
Interval -4.4 to 10.9
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Eosinophil, Week 28, Adj O, n=21
|
0.10 Percent change in counts
Interval -1.5 to 4.3
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Eosinophil, Week 28, Mono, n=61
|
0.30 Percent change in counts
Interval -3.3 to 10.8
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Eosinophil, Week 28, WD, n=33
|
-0.20 Percent change in counts
Interval -2.9 to 17.6
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Hematocrit, Week 15, Adj M, n=85
|
-0.01 Percent change in counts
Interval -0.11 to 0.06
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Hematocrit, Week 28, Adj O, n=19
|
-0.02 Percent change in counts
Interval -0.07 to 0.02
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Hematocrit, Week 28, Mono, n=55
|
-0.01 Percent change in counts
Interval -0.09 to 0.04
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Hematocrit, Week 28, WD, n=33
|
-0.00 Percent change in counts
Interval -0.04 to 0.1
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Lymphocytes, Week 15, Adj M, n=89
|
-2.10 Percent change in counts
Interval -25.8 to 18.9
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Lymphocytes, Week 28, Adj O, n=21
|
-2.40 Percent change in counts
Interval -16.0 to 13.6
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Lymphocytes, Week 28, Mono, n=61
|
-1.50 Percent change in counts
Interval -23.9 to 12.4
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Lymphocytes, Week 28, WD, n=33
|
-1.60 Percent change in counts
Interval -14.2 to 8.1
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Monocytes, Week 15, Adj M, n=89
|
0.00 Percent change in counts
Interval -8.9 to 6.5
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Monocytes, Week 28, Adj O, n=21
|
0.10 Percent change in counts
Interval -10.9 to 5.1
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Monocytes, Week 28, Mono, n=61
|
-0.20 Percent change in counts
Interval -6.4 to 9.5
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Monocytes, Week 28, WD, n=33
|
-0.30 Percent change in counts
Interval -8.0 to 8.1
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Total Neutrophils, Week 15, Adj M, n=89
|
1.3 Percent change in counts
Interval -26.3 to 30.4
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Total Neutrophils, Week 28, Adj O, n=21
|
0.50 Percent change in counts
Interval -13.8 to 16.8
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Total Neutrophils, Week 28, Mono, n=61
|
0.50 Percent change in counts
Interval -13.8 to 24.2
|
—
|
—
|
|
Percent Change From Baseline in the Basophil, Eosinophil, Hemoglobin, Lymphocyte, Monocyte, Absolute Neutrophil Count, Platelet Count, and White Blood Cell Count at the Indicated Time Points in the Study
Total Neutrophils, Week 28, WD, n=33
|
1.20 Percent change in counts
Interval -12.0 to 19.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the values of MCHC, albumin, and total protein at the indicated time points in the study from the respective Baseline values.
Outcome measures
| Measure |
LTG-XR Tablets
n=87 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
MCHC, Week 15, Adj M, n=85
|
-4.00 grams per liter
Interval -30.0 to 27.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
MCHC, Week 28, Adj O, n=21
|
1.00 grams per liter
Interval -18.0 to 26.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
MCHC, Week 28, Mono, n=61
|
-5.00 grams per liter
Interval -31.0 to 24.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
MCHC, Week 28, WD, n=33
|
1.00 grams per liter
Interval -25.0 to 15.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Albumin, Week 15, Adj M, n=87
|
0.00 grams per liter
Interval -5.0 to 7.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Albumin, Week 28, Adj O, n=20
|
-1.00 grams per liter
Interval -8.0 to 3.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Albumin, Week 28, Mono, n=61
|
0.00 grams per liter
Interval -6.0 to 6.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Albumin, Week 28, WD, n=33
|
0.00 grams per liter
Interval -9.0 to 6.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Total Protein, Week 15, WD, n=87
|
-1.0 grams per liter
Interval -13.0 to 8.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Total Protein, Week 28, WD, n=20
|
-3.00 grams per liter
Interval -11.0 to 3.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Total Protein, Week 28, WD, n=61
|
-1.0 grams per liter
Interval -15.0 to 6.0
|
—
|
—
|
|
Change From Baseline in the Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin, and Total Protein at the Indicated Time Points in the Study
Total Protein, Week 28, WD, n=33
|
-1.0 grams per liter
Interval -15.0 to 7.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of MCH at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=85 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points in the Study
Week 15, Adj M, n=85
|
-0.10 picograms
Interval -3.3 to 2.6
|
—
|
—
|
|
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points in the Study
Week 28, Adj O, n=19
|
0.10 picograms
Interval -1.2 to 1.6
|
—
|
—
|
|
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points in the Study
Week 28, Mono, n=55
|
-0.20 picograms
Interval -2.3 to 1.4
|
—
|
—
|
|
Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points in the Study
Week 28, WD, n=33
|
-0.20 picograms
Interval -1.9 to 3.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of MCV at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=85 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points in the the Study
Week 15, Adj M, n=85
|
0.00 Femtoliters
Interval -7.0 to 9.0
|
—
|
—
|
|
Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points in the the Study
Week 28, Adj O, n=19
|
-1.00 Femtoliters
Interval -7.0 to 5.0
|
—
|
—
|
|
Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points in the the Study
Week 28, Mono, n=55
|
1.00 Femtoliters
Interval -9.0 to 7.0
|
—
|
—
|
|
Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points in the the Study
Week 28, WD, n=33
|
0.00 Femtoliters
Interval -4.0 to 12.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of RBC count at the indicated time points in the study from the Baseline value. Change from baseline is measured as the number of red blood cells x 10\^12 per liter.
Outcome measures
| Measure |
LTG-XR Tablets
n=85 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points in the Study
Week 15, Adj M, n=85
|
-0.10 Tera (10^12) cells per liter
Interval -0.9 to 0.4
|
—
|
—
|
|
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points in the Study
Week 28, Adj O, n=19
|
-0.20 Tera (10^12) cells per liter
Interval -0.8 to 0.1
|
—
|
—
|
|
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points in the Study
Week 28, Mono, n=55
|
-0.10 Tera (10^12) cells per liter
Interval -0.7 to 0.4
|
—
|
—
|
|
Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points in the Study
Week 28, WD, n=33
|
0.00 Tera (10^12) cells per liter
Interval -0.5 to 1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of Alk P, Ala AT, and Asp AT at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=89 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Alk P, Week 15, Adj M, n=87
|
1.00 International units per liter
Interval -86.0 to 141.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Alk P, Week 28, Adj O, n=20
|
-0.50 International units per liter
Interval -72.0 to 20.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Alk P, Week 28, Mono, n=61
|
-5.0 International units per liter
Interval -118.0 to 49.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Alk P, Week 28, WD, n=33
|
2.00 International units per liter
Interval -90.0 to 90.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Ala-AT Week 15, Adj M, n=87
|
-2.00 International units per liter
Interval -30.0 to 71.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Ala-AT, Week 28, Adj O, n=20
|
-1.0 International units per liter
Interval -10.0 to 23.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Ala-AT, Week 28, Mono, n=61
|
-2.0 International units per liter
Interval -32.0 to 55.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Ala-AT, Week 28, WD, n=33
|
-2.0 International units per liter
Interval -20.0 to 7.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Asp-AT, Week 15, Adj M, n=87
|
-1.0 International units per liter
Interval -19.0 to 47.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Asp-AT, Week 28, WD, n=32
|
-3.0 International units per liter
Interval -34.0 to 7.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Asp-AT, Week 28, Adj O, n=20
|
-2.0 International units per liter
Interval -13.0 to 18.0
|
—
|
—
|
|
Change From Baseline in Alkaline Phosphatase (Alk P), Alanine Amino Transferase (Ala AT), and Aspartate Amino Transferase (Asp AT) at the Indicated Time Points in the Study
Asp-AT, Week 28, Mono, n=60
|
0.00 International units per liter
Interval -15.0 to 17.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of DB, TB, and creatinine at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=88 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
DB, Week 15, Adj M, n=87
|
0.0 micromoles (µmol) per liter
Interval -1.7 to 6.8
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
DB, Week 28, Adj O, n=20
|
0.0 micromoles (µmol) per liter
Interval -3.4 to 1.7
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
DB, Week 28, Mono, n=61
|
0.0 micromoles (µmol) per liter
Interval -1.7 to 12.0
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
DB, Week 28, WD, n=33
|
0.0 micromoles (µmol) per liter
Interval -1.7 to 1.7
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
TB, Week 15, Adj M, n=88
|
0.0 micromoles (µmol) per liter
Interval -8.6 to 15.4
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
TB, Week 28, Adj O, n=20
|
0.0 micromoles (µmol) per liter
Interval -3.4 to 1.7
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
TB, Week 28, Mono, n=61
|
1.7 micromoles (µmol) per liter
Interval -8.6 to 12.0
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
TB, Week 28, WD, n=33
|
0.0 micromoles (µmol) per liter
Interval -3.4 to 5.1
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
Creatinine, Week 15, Adj M, n=88
|
8.8 micromoles (µmol) per liter
Interval -17.7 to 53.0
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
Creatinine, Week 28, Adj O, n=20
|
8.8 micromoles (µmol) per liter
Interval 0.0 to 203.3
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
Creatinine, Week 28, Mono, n=61
|
8.8 micromoles (µmol) per liter
Interval -17.7 to 53.0
|
—
|
—
|
|
Change From Baseline in Direct Bilirubin (DB), Total Bilirubin (TB), and Creatinine at the Indicated Time Points in the Study
Creatinine, Week 28, WD, n=33
|
0.0 micromoles (µmol) per liter
Interval -17.7 to 17.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 0) and Week 15 (Adj M Phase), Week 28 (Adj O Phase), Week 28 (Mono Phase), and Week 28 (WD)Population: Safety Population. Only those participants with both a baseline and post-baseline value were analyzed.
The blood samples collected at the study visits were analyzed and assessed at the central laboratory, and the investigator reviewed and assessed the clinical significance. Change from Baseline was calculated by subtracting the value of cholesterol, HDL cholesterol, LDL cholesterol, glucose, potassium, sodium, triglycerides, and urea/BUN at the indicated time points in the study from the Baseline value.
Outcome measures
| Measure |
LTG-XR Tablets
n=87 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Sodium, Week 28, WD, n=33
|
1.0 millimoles (mmol) per liter
Interval -3.0 to 7.0
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Cholesterol, Week 15, Adj M, n=87
|
-0.1 millimoles (mmol) per liter
Interval -1.7 to 1.7
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Cholesterol, Week 28, Adj O, n=20
|
-0.1 millimoles (mmol) per liter
Interval -2.2 to 0.9
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Cholesterol, Week 28, Mono, n=61
|
-0.3 millimoles (mmol) per liter
Interval -2.5 to 1.2
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Cholesterol, Week 28, WD, n=33
|
-0.1 millimoles (mmol) per liter
Interval -3.5 to 1.0
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
HDL Cholesterol, Week 15, Adj M, n=87
|
0.1 millimoles (mmol) per liter
Interval -1.0 to 0.6
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
HDL Cholesterol, Week 28, Adj O, n=20
|
-0.0 millimoles (mmol) per liter
Interval -0.4 to 0.6
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
HDL Cholesterol, Week 28, Mono, n=61
|
0.0 millimoles (mmol) per liter
Interval -0.7 to 0.7
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
HDL Cholesterol, Week 28, WD, n=33
|
0.1 millimoles (mmol) per liter
Interval -0.9 to 0.4
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
LDL Cholesterol, Week 15, Adj M, n=86
|
-0.0 millimoles (mmol) per liter
Interval -1.1 to 1.2
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
LDL Cholesterol, Week 28, Adj O, n=19
|
-0.2 millimoles (mmol) per liter
Interval -1.9 to 1.1
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
LDL Cholesterol, Week 28, Mono, n=61
|
-0.1 millimoles (mmol) per liter
Interval -1.8 to 1.6
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
LDL Cholesterol, Week 28, WD, n=32
|
-0.1 millimoles (mmol) per liter
Interval -0.8 to 1.7
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Glucose, Week 15, Adj M, n=87
|
-0.1 millimoles (mmol) per liter
Interval -5.8 to 5.3
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Glucose, Week 28, Adj O, n=20
|
0.1 millimoles (mmol) per liter
Interval -6.7 to 6.7
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Glucose, Week 28, Mono, n=61
|
0.1 millimoles (mmol) per liter
Interval -3.6 to 6.4
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Glucose, Week 28, WD, n=33
|
0.3 millimoles (mmol) per liter
Interval -5.2 to 4.2
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Potassium, Week 15, Adj M, n=87
|
0.0 millimoles (mmol) per liter
Interval -1.2 to 1.1
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Potassium, Week 28, Adj O, n=20
|
-0.1 millimoles (mmol) per liter
Interval -0.7 to 1.2
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Potassium, Week 28, Mono, n=60
|
0.0 millimoles (mmol) per liter
Interval -1.3 to 1.2
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Potassium, Week 28, WD, n=32
|
0.0 millimoles (mmol) per liter
Interval -1.0 to 0.9
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Sodium, Week 15, Adj M, n=87
|
0.0 millimoles (mmol) per liter
Interval -4.0 to 6.0
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Sodium, Week 28, Adj O, n=20
|
0.5 millimoles (mmol) per liter
Interval -7.0 to 4.0
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Sodium, Week 28, Mono, n=61
|
-1.0 millimoles (mmol) per liter
Interval -5.0 to 9.0
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Triglyceride, Week 28, WD, n=87
|
-0.3 millimoles (mmol) per liter
Interval -2.3 to 0.9
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Triglyceride, Week 28, WD, n=20
|
-0.1 millimoles (mmol) per liter
Interval -1.7 to 1.6
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Triglyceride, Week 28, WD, n=61
|
-0.4 millimoles (mmol) per liter
Interval -1.9 to 1.1
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Triglyceride, Week 28, WD, n=33
|
1.0 millimoles (mmol) per liter
Interval -4.6 to 1.1
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Urea/BUN, Week 28, WD, n=87
|
0.0 millimoles (mmol) per liter
Interval -10.4 to 5.4
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Urea/BUN, Week 28, WD, n=20
|
0.5 millimoles (mmol) per liter
Interval -2.1 to 13.2
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Urea/BUN, Week 28, WD, n=61
|
0.0 millimoles (mmol) per liter
Interval -6.4 to 6.8
|
—
|
—
|
|
Change From Baseline in Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Glucose, Potassium, Sodium, Triglycerides, and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
Urea/BUN, Week 28, WD, n=33
|
0.4 millimoles (mmol) per liter
Interval -4.3 to 3.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 4, 7, 11, 15, 20, 24, and 28Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.
The blood samples were collected at the specified study visits; however, serum LTG concentrations were summarized by dose regimen, not by study week. The serum was assayed for LTG using an approved method under the management of Worldwide Bioanalysis, GlaxoSmithKline.
Outcome measures
| Measure |
LTG-XR Tablets
n=439 serum concentrations
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
n=243 serum concentrations
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
n=54 serum concentrations
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
500 mg, n=51, 121, 0
|
6.994 Micrograms per milliliter
Interval 0.931 to 13.412
|
3.974 Micrograms per milliliter
Interval 0.905 to 11.451
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
12.5 mg, n=0, 0, 1
|
NA Micrograms per milliliter
No dose was given for this regimen.
|
NA Micrograms per milliliter
No dose was given for this regimen.
|
0.957 Micrograms per milliliter
No full range is provided for the median value because only one participant was analyzed.
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
25 mg, n=0, 0, 8
|
NA Micrograms per milliliter
No dose was given for this regimen.
|
NA Micrograms per milliliter
No dose was given for this regimen.
|
1.362 Micrograms per milliliter
Interval 0.817 to 2.885
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
50 mg, n=30, 2, 8
|
1.281 Micrograms per milliliter
Interval 0.437 to 3.491
|
0.731 Micrograms per milliliter
Interval 0.727 to 0.734
|
2.972 Micrograms per milliliter
Interval 0.937 to 3.553
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
100 mg, n=40, 32, 6
|
3.425 Micrograms per milliliter
Interval 0.717 to 5.825
|
1.165 Micrograms per milliliter
Interval 0.442 to 4.254
|
4.723 Micrograms per milliliter
Interval 3.87 to 6.419
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
150 mg, n=11, 0, 6
|
5.653 Micrograms per milliliter
Interval 2.514 to 9.693
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
6.829 Micrograms per milliliter
Interval 3.549 to 10.804
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
200 mg, n=74, 22, 25
|
5.499 Micrograms per milliliter
Interval 1.449 to 12.926
|
1.583 Micrograms per milliliter
Interval 0.455 to 3.542
|
5.350 Micrograms per milliliter
Interval 3.301 to 13.75
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
225 mg, n=3, 0, 0
|
5.631 Micrograms per milliliter
Interval 4.815 to 5.642
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
250 mg, n=18, 11, 0
|
5.059 Micrograms per milliliter
Interval 2.329 to 10.969
|
4.073 Micrograms per milliliter
Interval 2.184 to 8.768
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
300 mg, n=193, 5, 0
|
5.493 Micrograms per milliliter
Interval 1.62 to 13.335
|
2.837 Micrograms per milliliter
Interval 1.898 to 3.558
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
350 mg, n=0, 3, 0
|
NA Micrograms per milliliter
No dose was given for this regimen.
|
4.084 Micrograms per milliliter
Interval 3.794 to 4.165
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
400 mg, n=19, 46, 0
|
7.322 Micrograms per milliliter
Interval 2.899 to 13.843
|
4.012 Micrograms per milliliter
Interval 1.459 to 9.675
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
|
Serum LTG Concentrations at Different LTG Doses Based on the Concomitant AED Groups: Neutral (Without Known Enzyme-inducing AED [EIAED], Valproate [VPA]) With EIAED, and With VPA
450 mg, n=0, 1, 0
|
NA Micrograms per milliliter
No dose was given for this regimen.
|
2.975 Micrograms per milliliter
No full range is provided for the median value because only one participant was analyzed.
|
NA Micrograms per milliliter
No participants were analyzed in this group at this dose level.
|
SECONDARY outcome
Timeframe: Weeks 4, 7, 11, 15, 20, 24, and 28Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.
Individual serum LTG concentration data were subjected to population pharmacokinetic methodologies based on the concomitant AED groups. Clearance is defined as the volume of LTG per unit time eliminated from serum. Serum LTG concentration-time data files incorporating, where appropriate, records of LTG administration, participant demography, and concomitant medication were supplied to Clinical Pharmacokinetics Modelling and Simulation, Clinical Pharmacology, and Discovery Medicine (CPDM) by Clinical Data Management as NONMEM compatible .csv files.
Outcome measures
| Measure |
LTG-XR Tablets
n=87 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
n=50 Participants
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
n=12 Participants
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Apparent Clearance (CL/F) Based on the Concomitant AED Groups: Neutral, With EIAED, and With VPA
|
1.91 Liters per hour
Interval 1.73 to 2.09
|
2.07 Liters per hour
Interval 1.69 to 2.46
|
-0.698 Liters per hour
Interval -0.96 to -0.441
|
SECONDARY outcome
Timeframe: Weeks 4, 7, 11, 15, 20, 24, and 28Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.
Individual serum LTG concentration data were subjected to population pharmacokinetic methodologies based on the concomitant AED groups. V/F is defined as the apparent volume in which a drug is distributed immediately after it has been injected intravenously and equilibrated between plasma and the surrounding tissues. Serum LTG concentration-time data files incorporating, where appropriate, records of LTG administration, participant demography, and concomitant medication were supplied to CPDM by Clinical Data Management as NONMEM compatible .csv files.
Outcome measures
| Measure |
LTG-XR Tablets
n=149 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Apparent Volume of Distribution (V/F) for Participants in All Concomitant AED Groups Combined: Neutral, With EIAED, and With VPA
|
26.8 liters
Interval 7.4 to 46.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 4, 7, 11, 15, 20, 24, and 28Population: Safety Population. Participants with missing data were not analyzed. Not all participants received all doses at each blood draw; therefore, participants were only analyzed for the dose received at blood draw.
Individual serum LTG concentration data were subjected to population pharmacokinetic methodologies based on the concomitant AED groups. KA is defined as the rate at which a drug enters the body after administration. Serum LTG concentration-time data files incorporating, where appropriate, records of LTG administration, participant demography, and concomitant medication were supplied to CPDM by Clinical Data Management as NONMEM compatible .csv files.
Outcome measures
| Measure |
LTG-XR Tablets
n=149 Participants
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + EIAEDs
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included EIAEDs), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
LTG-XR + VPA
LTG-XR tablets (25, 50, 100, and 200 mg) were administered OD in the 7-w Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant AED (included VPA), followed by an 8-w Adjunctive Maintenance Phase: LTG-XR tablets administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|---|---|
|
Absorption Rate (KA) for Participants in All Concomitant AED Groups Combined: Neutral, With EIAED, and With VPA
|
0.0325 1/h
Interval 0.0105 to 0.0549
|
—
|
—
|
Adverse Events
LTG-XR Tablets
Serious events: 22 serious events
Other events: 98 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LTG-XR Tablets
n=121 participants at risk
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|
|
Injury, poisoning and procedural complications
Hip fracture
|
2.5%
3/121
|
|
Nervous system disorders
Ataxia
|
1.7%
2/121
|
|
Nervous system disorders
Convulsion
|
1.7%
2/121
|
|
Nervous system disorders
Status epilepticus
|
1.7%
2/121
|
|
Cardiac disorders
Acute myocardial infarction
|
0.83%
1/121
|
|
Nervous system disorders
Balance disorder
|
0.83%
1/121
|
|
Cardiac disorders
Cardiac failure congestive
|
0.83%
1/121
|
|
Nervous system disorders
Cerebrovascular accident
|
0.83%
1/121
|
|
Gastrointestinal disorders
Colitis
|
0.83%
1/121
|
|
Infections and infestations
Diverticulitis
|
0.83%
1/121
|
|
Infections and infestations
Gastroenteritis
|
0.83%
1/121
|
|
Nervous system disorders
Grand mal convulsion
|
0.83%
1/121
|
|
Vascular disorders
Hypertension
|
0.83%
1/121
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.83%
1/121
|
|
Nervous system disorders
Lethargy
|
0.83%
1/121
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.83%
1/121
|
|
Gastrointestinal disorders
Nausea
|
0.83%
1/121
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.83%
1/121
|
|
General disorders
Non-cardiac chest pain
|
0.83%
1/121
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.83%
1/121
|
|
Infections and infestations
Pneumonia
|
0.83%
1/121
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.83%
1/121
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.83%
1/121
|
|
Nervous system disorders
Syncope
|
0.83%
1/121
|
|
Vascular disorders
Thrombosis
|
0.83%
1/121
|
|
Nervous system disorders
Toxic encephalopathy
|
0.83%
1/121
|
|
Infections and infestations
Urinary tract infection
|
0.83%
1/121
|
Other adverse events
| Measure |
LTG-XR Tablets
n=121 participants at risk
LTG-XR tablets (25, 50, 100, and 200 milligrams \[mg\]) administered once a day (OD) in the 7-week (w) Dose-Escalation Phase and titrated to target doses of 300, 500, or 200 mg/day for participants (par.) depending on their concomitant antiepileptic drug (AED), followed by an 8-w Adjunctive Maintenance Phase in which LTG-XR tablets were administered OD at the target dose. Par. on a single concomitant AED who converted to LTG-XR monotherapy (based on investigator's judgment) entered the 5-w Conversion Phase, followed by an 8-w Monotherapy Phase, whereas par. who did not transition to monotherapy entered the 13-w Adjunctive Optimization Phase. At the end of the study, par. entered the 2- to 5-w Taper/Follow-Up Phase, in which par. either switched to commercial LTG (received same total daily dose of commercial LTG in 2 divided doses \[BID\]) or did not switch to commercial LTG (current dose was reduced by approximately one-fourth per week) with a final visit 2 weeks after last LTG-XR dose.
|
|---|---|
|
Nervous system disorders
Dizziness
|
25.6%
31/121
|
|
Nervous system disorders
Balance disorder
|
20.7%
25/121
|
|
Injury, poisoning and procedural complications
Fall
|
18.2%
22/121
|
|
Nervous system disorders
Headache
|
17.4%
21/121
|
|
Nervous system disorders
Tremor
|
16.5%
20/121
|
|
Nervous system disorders
Fatigue
|
14.0%
17/121
|
|
Gastrointestinal disorders
Nausea
|
14.0%
17/121
|
|
Skin and subcutaneous tissue disorders
All rash
|
11.6%
14/121
|
|
Nervous system disorders
Ataxia
|
11.6%
14/121
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
9.9%
12/121
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
11/121
|
|
Musculoskeletal and connective tissue disorders
Pain In extremity
|
9.1%
11/121
|
|
Nervous system disorders
Gait disturbance
|
8.3%
10/121
|
|
Nervous system disorders
Somnolence
|
8.3%
10/121
|
|
Nervous system disorders
Arthralgia
|
7.4%
9/121
|
|
Nervous system disorders
Confusional state
|
6.6%
8/121
|
|
Gastrointestinal disorders
Constipation
|
6.6%
8/121
|
|
Gastrointestinal disorders
Decreased appetite
|
6.6%
8/121
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.8%
7/121
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.8%
7/121
|
|
Skin and subcutaneous tissue disorders
Skin laceration
|
5.8%
7/121
|
|
Renal and urinary disorders
Urinary tract infection
|
5.8%
7/121
|
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