Trial Outcomes & Findings for Conversion to Monotherapy Study With Keppra XR for Partial Seizures (NCT NCT00419094)
NCT ID: NCT00419094
Last Updated: 2014-09-05
Results Overview
Cumulative exit rate at day 112, based on the duration between start date of previous AED tapering to the earliest date exit criterion was met; calculated using Kaplan Meier Methods. Subjects prematurely discontinued for reasons unrelated to exit criteria were censored as of last dose of study drug. Subjects who completed without meeting exit criteria were censored at Day 112. Exit criteria include increase in seizure frequency, severity, duration, status epilepticus, or new generalized seizure. Upper 95% 2-sided confidence limit for exit rate is compared to the historical control rate: 0.678.
COMPLETED
PHASE3
228 participants
112 days
2014-09-05
Participant Flow
The Efficacy (EFF) population is defined as all subjects in the Intent to Treat (ITT) population who enter into the Previous Antiepileptic (AED) Discontinuation (D/C) Phase. The Per Protocol (PP) population consists of all subjects in the EFF population who have no important protocol deviations related to efficacy.
Subjects are to be randomized into treatment with either Keppra XR 2000 mg/day or Keppra XR 1000 mg/day in a 3:1 ratio.
Participant milestones
| Measure |
Keppra XR 1000 mg/Day
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
Overall Study
STARTED
|
57
|
171
|
|
Overall Study
COMPLETED
|
50
|
141
|
|
Overall Study
NOT COMPLETED
|
7
|
30
|
Reasons for withdrawal
| Measure |
Keppra XR 1000 mg/Day
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
7
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
2
|
|
Overall Study
Protocol Violation
|
1
|
14
|
|
Overall Study
Withdrawal of consent
|
1
|
5
|
|
Overall Study
Other: Error determining exit criteria
|
1
|
0
|
|
Overall Study
Other: Patient non-compliant
|
0
|
1
|
|
Overall Study
Other: No contact for extended period
|
0
|
1
|
Baseline Characteristics
Conversion to Monotherapy Study With Keppra XR for Partial Seizures
Baseline characteristics by cohort
| Measure |
Keppra XR 1000 mg/Day
n=57 Participants
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
n=171 Participants
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
Total
n=228 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
11 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
43 Participants
n=5 Participants
|
140 Participants
n=7 Participants
|
183 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
33.48 years
STANDARD_DEVIATION 16.32 • n=5 Participants
|
34.31 years
STANDARD_DEVIATION 13.69 • n=7 Participants
|
34.11 years
STANDARD_DEVIATION 14.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
132 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
29 participants
n=7 Participants
|
37 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
17 participants
n=5 Participants
|
43 participants
n=7 Participants
|
60 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
16 participants
n=5 Participants
|
51 participants
n=7 Participants
|
67 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
16 participants
n=5 Participants
|
48 participants
n=7 Participants
|
64 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 112 daysPopulation: Of the 171 (Keppra 2000 mg) subjects randomized, 158 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population. Primary Efficacy analysis was conducted for the Keppra XR 2000 mg/day group only.
Cumulative exit rate at day 112, based on the duration between start date of previous AED tapering to the earliest date exit criterion was met; calculated using Kaplan Meier Methods. Subjects prematurely discontinued for reasons unrelated to exit criteria were censored as of last dose of study drug. Subjects who completed without meeting exit criteria were censored at Day 112. Exit criteria include increase in seizure frequency, severity, duration, status epilepticus, or new generalized seizure. Upper 95% 2-sided confidence limit for exit rate is compared to the historical control rate: 0.678.
Outcome measures
| Measure |
Keppra XR 1000 mg/Day
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
n=158 Participants
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
The Cumulative Exit Rate at 112 Days After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase
|
—
|
0.375 proportion of subjects
Interval 0.297 to 0.453
|
SECONDARY outcome
Timeframe: 112 daysPopulation: Of the 171 (Keppra 2000 mg) subjects randomized, 158 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population. Evaluated for Keppra XR 2000 mg/day only.
The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who prematurely discontinued for reasons unrelated to exit criteria, adverse event, or lack of efficacy were censored as of the last dose of study medication. Subjects who completed the study without having an exit event were censored as of Day 112.
Outcome measures
| Measure |
Keppra XR 1000 mg/Day
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
n=158 Participants
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
The Cumulative Rate of Exit Events, Which Include Discontinuation Due to Exit Criteria, Withdrawal Due to Adverse Events (AE) and Withdrawal Due to Lack of Efficacy, at 112 Days After the Beginning of Previous Antiepileptic Drug (AED) Tapering Phase
|
—
|
0.385 proportion of subjects
Interval 0.307 to 0.463
|
SECONDARY outcome
Timeframe: 112 daysPopulation: Of the 171 (Keppra 2000 mg) subjects randomized, 158 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population. Evaluated for Keppra XR 2000 mg/day only.
The cumulative exit event rate at Day 112 was calculated using Kaplan Meier methods. The exit event rate estimate was based on the duration between the start date of previous AED tapering to the earliest date an exit event occured. Subjects who completed the study without having an exit event were censored as of Day 112.
Outcome measures
| Measure |
Keppra XR 1000 mg/Day
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
n=158 Participants
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
The Cumulative Rate of Exit Events Due to Any Reasons at 112 Days After the Beginning of Previous Antiepileptic Drug (AED) Tapering Phase
|
—
|
0.475 proportion of subjects
Interval 0.397 to 0.553
|
SECONDARY outcome
Timeframe: 112 daysPopulation: Of the 57 (Keppra 1000 mg) subjects randomized, 54 subjects entered the Previous Antiepileptic Drug Tapering Phase and were included in the Efficacy Population.
Keppra XR 1000 mg arm was not intended for inferential analysis (planned 3 to 1 randomization, Keppra XR 2000 mg: 1000 mg). The Exit Rate was based on the duration between the start date of previous AED tapering to the earliest date an exit crterion was met. Subjects who prematurely discontinued for reasons unrelated to exit criteria were censored as of the last dose of study medication. Subjects who completed the study without meeting an exit criterion were censored as of Day 112.
Outcome measures
| Measure |
Keppra XR 1000 mg/Day
n=54 Participants
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
The Cumulative Exit Rate at 112 Days for the Keppra XR 1000 mg Group After the Beginning of the Previous Antiepileptic Drug (AED) Tapering Phase
|
0.334 proportion of subjects
Interval 0.204 to 0.465
|
—
|
Adverse Events
Keppra XR 1000 mg/Day
Keppra XR 2000 mg/Day
Serious adverse events
| Measure |
Keppra XR 1000 mg/Day
n=57 participants at risk
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
n=171 participants at risk
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
Gastrointestinal disorders
haemorrhoidal haemorrhage
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Gastrointestinal disorders
pancreatitis acute
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Infections and infestations
pulmonary tuberculosis
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Infections and infestations
pyelonephritis
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Injury, poisoning and procedural complications
ankle fracture
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Musculoskeletal and connective tissue disorders
back pain
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Musculoskeletal and connective tissue disorders
intervertebral disc protrusion
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Musculoskeletal and connective tissue disorders
lumbar spinal stenosis
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Nervous system disorders
convulsion
|
1.8%
1/57 • Number of events 1 • Up to 29 weeks
|
2.3%
4/171 • Number of events 4 • Up to 29 weeks
|
|
Nervous system disorders
status epilepticus
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
|
Psychiatric disorders
acute psychosis
|
1.8%
1/57 • Number of events 1 • Up to 29 weeks
|
0.00%
0/171 • Up to 29 weeks
|
|
Vascular disorders
thrombosis
|
0.00%
0/57 • Up to 29 weeks
|
0.58%
1/171 • Number of events 1 • Up to 29 weeks
|
Other adverse events
| Measure |
Keppra XR 1000 mg/Day
n=57 participants at risk
1000 mg/day once daily for 18 weeks (administered as two Keppra XR tablets and two placebo tablets once daily)
|
Keppra XR 2000 mg/Day
n=171 participants at risk
2000 mg/day once daily for 18 weeks (administered as four Keppra XR tablets once daily)
|
|---|---|---|
|
Ear and labyrinth disorders
vertigo
|
5.3%
3/57 • Number of events 3 • Up to 29 weeks
|
4.1%
7/171 • Number of events 7 • Up to 29 weeks
|
|
Gastrointestinal disorders
abdominal pain
|
5.3%
3/57 • Number of events 3 • Up to 29 weeks
|
3.5%
6/171 • Number of events 6 • Up to 29 weeks
|
|
General disorders
irritablility
|
5.3%
3/57 • Number of events 3 • Up to 29 weeks
|
7.0%
12/171 • Number of events 12 • Up to 29 weeks
|
|
Infections and infestations
nasopharyngitis
|
5.3%
3/57 • Number of events 3 • Up to 29 weeks
|
4.1%
7/171 • Number of events 7 • Up to 29 weeks
|
|
Nervous system disorders
somnolence
|
21.1%
12/57 • Number of events 13 • Up to 29 weeks
|
22.2%
38/171 • Number of events 40 • Up to 29 weeks
|
|
Nervous system disorders
headache
|
22.8%
13/57 • Number of events 34 • Up to 29 weeks
|
18.7%
32/171 • Number of events 55 • Up to 29 weeks
|
|
Nervous system disorders
convulsion
|
15.8%
9/57 • Number of events 9 • Up to 29 weeks
|
11.7%
20/171 • Number of events 20 • Up to 29 weeks
|
|
Nervous system disorders
dizziness
|
5.3%
3/57 • Number of events 4 • Up to 29 weeks
|
8.8%
15/171 • Number of events 19 • Up to 29 weeks
|
Additional Information
Study Director
UCB, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee UCB has \> 60 days but \<= 180 days to review results communications prior to public release and may delete information that is confidential and compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
- Publication restrictions are in place
Restriction type: OTHER