Trial Outcomes & Findings for A Double-blind, Placebo-controlled Study of Levetiracetam in Epilepsy Patients With Generalized Tonic-clonic Seizures (Except Partial Seizures Evolving to Secondarily Generalized Seizures) (NCT NCT01228747)

Results Overview

Percentage change in generalized tonic-clonic (GTC) seizure frequency per week from Combined Baseline B over the Treatment Period A is calculated using the equation: Percentage change from Baseline = ((A-B)/B)\*100. Percentage change from baseline is not defined for subjects whose baseline information is missing / unknown or equal to zero, or whose seizure frequency per week is missing / unknown. A negative value in change in generalized tonic-clonic (GTC) seizure frequency indicates a reduction of generalized tonic-clonic (GTC) seizure frequency over the 28-week treatment Period. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

361 participants

Primary outcome timeframe

From Baseline to Week 28

Results posted on

2025-04-03

Participant Flow

This study started to enroll subjects in Japan and China in October 2010.

Participant Flow refers to the Randomized Set consisting of all screened subjects who signed the Informed Consent form, participated in the prospective Baseline Period and were randomized at Visit 2.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
Overall Study STARTED	125	126
Overall Study COMPLETED	60	81
Overall Study NOT COMPLETED	65	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
Overall Study Adverse Event	8	4
Overall Study Lack of Efficacy	40	27
Overall Study Protocol Violation	6	5
Overall Study Lost to Follow-up	4	3
Overall Study Withdrawal by Subject	5	1
Overall Study Other Reason	2	5

Baseline Characteristics

A Double-blind, Placebo-controlled Study of Levetiracetam in Epilepsy Patients With Generalized Tonic-clonic Seizures (Except Partial Seizures Evolving to Secondarily Generalized Seizures)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=125 Participants Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily	Levetiracetam n=126 Participants Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily	Total n=251 Participants Total of all reporting groups
Age, Categorical <=18 years	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	113 Participants n=5 Participants	115 Participants n=7 Participants	228 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	32.8 years STANDARD_DEVIATION 12.5 • n=5 Participants	31.5 years STANDARD_DEVIATION 11.3 • n=7 Participants	32.2 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	47 Participants n=7 Participants	96 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	79 Participants n=7 Participants	155 Participants n=5 Participants
Region of Enrollment China	104 participants n=5 Participants	104 participants n=7 Participants	208 participants n=5 Participants
Region of Enrollment Japan	21 participants n=5 Participants	22 participants n=7 Participants	43 participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 28

Population: Full Analysis Set consisted of all subjects in the SS who had an evaluable Baseline and at least 1 post-Baseline GTC seizure count data point for the primary efficacy analysis excluding those who had seriously violated GCP. Evaluable Baseline for the primary efficacy analysis: at least 1 GTC seizure was documented for the Combined Baseline.

Percentage change in generalized tonic-clonic (GTC) seizure frequency per week from Combined Baseline B over the Treatment Period A is calculated using the equation: Percentage change from Baseline = ((A-B)/B)\*100. Percentage change from baseline is not defined for subjects whose baseline information is missing / unknown or equal to zero, or whose seizure frequency per week is missing / unknown. A negative value in change in generalized tonic-clonic (GTC) seizure frequency indicates a reduction of generalized tonic-clonic (GTC) seizure frequency over the 28-week treatment Period. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam n=117 Participants Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
Percentage Change From the Combined Baseline in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 28-week Treatment Period (Dose Adjustment + Evaluation Periods)	-13.19 Percentage Change Standard Deviation 55.54	-68.22 Percentage Change Standard Deviation 34.95

SECONDARY outcome

Timeframe: From Baseline to Evaluation Period (Week 12 to Week 28)

Population: Of the 226 subjects in the Full Analysis Set (FAS), 205 are included in the analysis of this Outcome Measure in Evaluation Period.

Percentage change in generalized tonic-clonic (GTC) seizure frequency per week from combined baseline B over the Evaluation Period A is calculated using the equation: Percentage change from Baseline = ((A-B)/B)\*100. Percentage change from baseline is not defined for subjects whose baseline Information is missing / unknown or equal to zero, or whose seizure frequency per week is missing / unknown. A negative value in change in generalized tonic-clonic (GTC) seizure frequency indicates a reduction of generalized tonic-clonic (GTC) seizure frequency. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam n=108 Participants Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
The Percentage Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Over the Evaluation Period	-4.44 Percentage Change Standard Deviation 153.82	-68.27 Percentage Change Standard Deviation 42.63

SECONDARY outcome

Timeframe: From Baseline to Week 28

Population: Full Analysis Set consisted of all subjects in the SS who had an evaluable Baseline and at least 1 post-Baseline GTC seizure count data point for the primary efficacy analysis excluding those who had seriously violated GCP. Evaluable Baseline for the primary efficacy analysis: at least 1 GTC seizure was documented for the Combined Baseline.

A subject with an at least 50 % reduction in weekly generalized tonic-clonic (GTC) seizure frequency from Combined Baseline Period to the Treatment Period is considered a GTC 50 % responder. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline

Outcome measures

Outcome measures
Measure	Placebo n=109 Participants Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam n=117 Participants Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Treatment Period	31 participants	91 participants

SECONDARY outcome

Timeframe: From Baseline to Evaluation Period (Week 12 to Week 28)

Population: Of the 226 subjects in the Full Analysis Set (FAS), 205 are included in the analysis of this Outcome Measure.

A subject with an at least 50 % reduction in weekly generalized tonic-clonic (GTC) seizure frequency from Combined Baseline Period to the Evaluation Period is considered a GTC 50 % responder. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam n=108 Participants Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Evaluation Period	33 participants	82 participants

SECONDARY outcome

Timeframe: Evaluation Period (Week 12 to Week 28)

Population: Of the 226 subjects in the Full Analysis Set (FAS), 205 are included in the analysis of this Outcome Measure.

A subject with a non-missing weekly generalized tonic-clonic (GTC) baseline seizure frequency and a weekly GTC seizure frequency of zero throughout the Evaluation Period, is considered as a GTC seizure-free subject on the Evaluation Period.

Outcome measures

Outcome measures
Measure	Placebo n=97 Participants Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam n=108 Participants Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period	3 participants	32 participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 32 other events

Deaths: 0 deaths

Levetiracetam

Serious events: 1 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=125 participants at risk Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam n=126 participants at risk Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
General disorders Drowning	1.6% 2/125 • Number of events 2 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	0.00% 0/126 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.
General disorders Sudden unexplained death in epilepsy	0.80% 1/125 • Number of events 1 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	0.00% 0/126 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.
Infections and infestations Pneumonia	0.00% 0/125 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	0.79% 1/126 • Number of events 1 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.
Nervous system disorders Epilepsy	0.80% 1/125 • Number of events 1 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	0.00% 0/126 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.

Other adverse events

Other adverse events
Measure	Placebo n=125 participants at risk Matching placebo for 28 weeks Placebo: Matching oral placebo tablets twice daily for 28 weeks	Levetiracetam n=126 participants at risk Levetiracetam treatment with dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks Levetiracetam: Oral dose tablets, twice daily
General disorders Pyrexia	4.0% 5/125 • Number of events 5 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	5.6% 7/126 • Number of events 8 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.
Infections and infestations Nasopharyngitis	16.0% 20/125 • Number of events 36 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	19.0% 24/126 • Number of events 33 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.
Investigations Platelet count decreased	3.2% 4/125 • Number of events 4 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	5.6% 7/126 • Number of events 8 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.
Investigations Protein urine present	0.80% 1/125 • Number of events 1 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	7.9% 10/126 • Number of events 11 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.
Nervous system disorders Dizziness	7.2% 9/125 • Number of events 14 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.	3.2% 4/126 • Number of events 7 • Adverse Events were collected from the Prospective Baseline Period ( Week -8 to Week 0) over Dose Adjustment (12 weeks) and Evaluation Period (16 weeks) until Conversion or Withdrawal Period (4-6 weeks). Adverse Events refer to the Safety Set (SS), which is a subset of the Randomized Set and consisted of all subjects who received at least 1 dose of study medication after randomization, either Placebo or Levetiracetam. Adverse Events were presented for the Dose Adjustment and Evaluation Period.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: +1 877 822 9493 (UCB)

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60