Levetiracetam Versus Topiramate as Adjunctive Therapy to... | NCT01229735

NCT01229735

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Levetiracetam	Experimental	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks	Drug: Levetiracetam
Topiramate	Active Comparator	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks	Drug: Topiramate

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Levetiracetam	Drug	250 mg and 500 mg levetiracetam tablet 1000 mg/day (500 mg bid) levetiracetam (maximum to 3000 mg/day) Duration: maximum 52 weeks	Levetiracetam

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Subjects Continuing the Allocated Investigational Treatment From the First Study Treatment Intake to Week 52, After the Beginning of Investigational Treatment With Levetiracetam Compared to Topiramate		From Baseline to Week 52

Secondary Outcomes

Measure	Description	Time Frame
Number of Subjects With at Least One Adverse Event Reported During the Trial Period From Baseline to Week 52		From Baseline to Week 52
Time From the First Study Treatment Intake to Drug Discontinuation Due to Adverse Event (AE)		From Baseline to Week 52

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female subjects from 16 to 80 years, inclusive. Subjects under 20 years may only be included where legally permitted and ethically accepted
Subjects with refractory epilepsy with partial onset seizure classifiable according to the International League Against Epilepsy (ILAE).
Subjects having at least 2 partial onset seizures whether or not secondarily generalized during the 8 weeks historical baseline preceding V1 according to ILAE classification
Subjects having at least 1 partial onset seizures whether or not secondarily generalized per 4 weeks preceding V2 according to ILAE classification
Subjects with each interval of partial onset seizures less than 6 weeks during entire 12 weeks (8 weeks preceding V1 and 4 weeks preceding V2)
Subjects being uncontrolled while treated by 1 to 3 permitted concomitant AEDs.
Permitted concomitant AEDs having been stable and at optimal dosage for the subject from at least 4 week before V1 and during 4 weeks preceding V2 and expected to be kept stable during the Treatment Period.

Exclusion Criteria:

Subjects presenting any generalized epilepsies classified as type II according to the ILAE classification (ref to publication from 1981)
Subjects suffering from epilepsies and syndromes undetermined whether focal or generalized (classification III according to the ILAE classification)
Subjects suffering from special syndromes (classification IV according to the ILAE classification)
History or occurring only in clusters (too frequently or indistinctly separated to be reliably counted) before V2.
Presence of exclusively type IA non-motor seizures.
History or presence of status epilepticus within last 3 months preceding V1 or during Baseline
History or presence of known pseudo-seizures
Subjects who are currently on vigabatrin. (Subjects who received vigabatrin in the past and have a normal visual field test are allowed.)
Subject taking 1 or more of the following medications on a regular basis within 28 days prior to Visit 1: antipsychotics drugs, and psychostimulant (amphetamine derivatives)

Contacts/Locations Module

Name	Affiliation	Role
UCB Clinical Trial Call Center	1 877 822 9493 (UCB)	Study Director

References Module

Label	URL
FDA Safety Alerts and Recalls	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Levetiracetam	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks
FG001	Topiramate

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks

The Baseline Characteristics refers to the Safety Set which consists of all subjects who were randomized and received at least 1 dose of trial medication.

Arm/Group Information

ID	Title	Description
BG000	Levetiracetam	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks
BG001	Topiramate	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks
BG002	Total Title

Units	Counts
Participants	BG000177 BG001166 BG002343

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0004 BG0010 BG0024
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00040.9± 13.6 BG00139.7± 11.8 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00071 BG00164 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Subjects Continuing the Allocated Investigational Treatment From the First Study Treatment Intake to Week 52, After the Beginning of Investigational Treatment With Levetiracetam Compared to Topiramate

The Full Analysis Set (FAS) consisted of all subjects in the Safety Set who returned at least 1 post-baseline seizure diary.

Posted

Number

percentage of subjects

From Baseline to Week 52

ID	Title	Description
OG000	Levetiracetam (Full Analysis Set)	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks
OG001	Topiramate (Full Analysis Set)	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks

Units	Counts
Participants	OG000176 OG001166

Title

Denominators

Categories

Title	Measurements
	OG00059.1 OG00156.6

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The Odds Ratio (OR) for LEV vs TPM is based on logistic regression modeling of subject retention by treatment and center pooling category. A profile likelihood confidence interval for the OR is presented.	Regression, Logistic		=0.7007	P-value is from likelihood ratio test of treatment group regression coefficient against 0.	Odds Ratio (OR)	1.1			2-Sided	95	0.7	1.7					Superiority or Other

Secondary

Number of Subjects With at Least One Adverse Event Reported During the Trial Period From Baseline to Week 52

The Safety Set (SS) consists of all subjects who were randomized and received at least 1 (partial) dose of study medication.

Posted

Number

Participants

From Baseline to Week 52

ID	Title	Description
OG000	Levetiracetam	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks
OG001	Topiramate	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks

Units	Counts
Participants	OG000

Secondary

Time From the First Study Treatment Intake to Drug Discontinuation Due to Adverse Event (AE)

The Safety Set (SS) consists of all subjects who were randomized and received at least 1 (partial) dose of study medication.

Posted

Median

Inter-Quartile Range

month

From Baseline to Week 52

ID	Title	Description
OG000	Levetiracetam	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks
OG001	Topiramate	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks

Units	Counts
Participants	OG000

Secondary

Median Percent Reduction in the Weekly Partial Onset Seizure (POS) Frequency From Baseline During the Total Treatment Period From Baseline to Week 52

Reduction from baseline was defined as baseline value minus post-baseline value and therefore is the negative of the change from baseline value.

The Full Analysis Set (FAS) consists of all subjects in the Safety Set (SS) who returned at least 1 postbaseline seizure diary.

Posted

Median

Inter-Quartile Range

percent reduction

From Baseline to Week 52

ID	Title	Description
OG000	Levetiracetam (Full Analysis Set)	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks
OG001	Topiramate (Full Analysis Set)	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks

Units	Counts
Participants

Secondary

Responders Defined as Number of Subjects With at Least 50 % Reduction in the Weekly POS Frequency From Baseline During the Total Treatment Period From Baseline to Week 52

The Full Analysis Set (FAS) consists of all subjects in the SS who returned at least 1 postbaseline seizure diary.

Posted

Number

responders

From Baseline to Week 52

ID	Title	Description
OG000	Levetiracetam (Full Analysis Set)	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks
OG001	Topiramate (Full Analysis Set)	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Levetiracetam	250 mg and 500 mg levetiracetam tablet; titration from 1000 mg/day (500 mg bid) to 3000 mg/day (1500 mg bid) levetiracetam with treatment duration up to 52 weeks			10	177	86	177
EG001	Topiramate	25 mg and 100 mg topiramate tablet; titration from 100 mg/day (50 mg bid) to 400 mg/day (200 mg bid) topiramate with treatment duration up to 52 weeks			15	166	91	166

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Arrhythmia	Cardiac disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Arteriovenous malformation	Congenital, familial and genetic disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Atrial septal defect	Congenital, familial and genetic disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Photophobia	Eye disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Alcoholic pancreatitis	Gastrointestinal disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Ileus	Gastrointestinal disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Asthenia	General disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Chronic tonsillitis	Infections and infestations	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Pneumonia	Infections and infestations	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Face injury	Injury, poisoning and procedural complications	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Fall	Injury, poisoning and procedural complications	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA18.0	Non-systematic Assessment	EG0002 events1 affected177 at risk EG0010 events0 affected166 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Dizziness	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0002 events2 affected177 at risk EG0010 events0 affected166 at risk
Dyskinesia	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Headache	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Loss of consciousness	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Seizure	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0016 events5 affected166 at risk
Stupor	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0010 events0 affected166 at risk
Epilepsy	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk
Deep vein thrombosis	Vascular disorders	MedDRA18.0	Non-systematic Assessment	EG0000 events0 affected177 at risk EG0011 events1 affected166 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dyspepsia	Gastrointestinal disorders	MedDRA18.0	Non-systematic Assessment	EG00010 events9 affected177 at risk EG0018 events7 affected166 at risk
Nausea	Gastrointestinal disorders	MedDRA18.0	Non-systematic Assessment	EG00011 events9 affected177 at risk EG00110 events10 affected166 at risk
Nasopharyngitis	Infections and infestations	MedDRA18.0	Non-systematic Assessment	EG00032 events24 affected177 at risk EG00122 events16 affected166 at risk
Weight decreased	Investigations	MedDRA18.0	Non-systematic Assessment	EG0003 events3 affected177 at risk EG00119 events17 affected166 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA18.0	Non-systematic Assessment	EG0003 events3 affected177 at risk EG00132 events26 affected166 at risk
Somnolence	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG00040 events36 affected177 at risk EG00121 events20 affected166 at risk
Dizziness	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG00047 events30 affected177 at risk EG00129 events24 affected166 at risk
Headache	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG00024 events17 affected177 at risk EG00125 events24 affected166 at risk
Tremor	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0009 events9 affected177 at risk EG0010 events0 affected166 at risk
Memory impairment	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0001 events1 affected177 at risk EG0019 events9 affected166 at risk
Paraesthesia	Nervous system disorders	MedDRA18.0	Non-systematic Assessment	EG0002 events2 affected177 at risk EG00119 events16 affected166 at risk

ID	Term
D004827	Epilepsy
D012640	Seizures

Ancestor Terms

ID	Term
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000077287	Levetiracetam
D000077236	Topiramate

Ancestor Terms

ID	Term
D000081	Acetamides
D000577	Amides
D009930	Organic Chemicals
D000085	Acetates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D011760	Pyrrolidinones
D011759	Pyrrolidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D005632	Fructose
D006601	Hexoses
D009005	Monosaccharides
D000073893	Sugars
D002241	Carbohydrates
D007661	Ketoses

Facility	Status	City	State	ZIP	Country	Contacts
14		Busan			South Korea
21