Levetiracetam Versus Standard Antiepileptic Drugs (Carbamazepine and Valproate) Used as Monotherapy in Patients With Newly Diagnosed Epilepsy

• ClinicalTrials.gov Identifier: NCT00175903
• Recruitment Status: Completed
• First Posted: September 15, 2005
• Last Update Posted: March 17, 2015
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

Study Description

Brief Summary:

Study N01175 was to compare overall effectiveness (efficacy and safety) of levetiracetam (LEV) versus the 2 older antiepileptic drugs (AEDs), sodium valproate extended release (VPA-ER) and carbamazepine controlled release (CBZ-CR) in the treatment of subjects with newly diagnosed epilepsy.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Levetiracetam; Drug: Carbamazepine Controlled Release (CBZ-CR); Drug: Valproate Extended Release	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1701 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Therapeutic Confirmatory, Open-label, Multi-center, Randomized 2 Parallel Groups, Community-based Trial Studying the Efficacy and Safety of Levetiracetam (1000 to 3000 mg/Day Oral Tablets 250-500 mg b.i.d.) Compared to Sodium Valproate (1000 to 2000 mg/Day Oral ER Tablets 300-500 mg b.i.d.) and Carbamazepine (600 to 1600 mg/Day Oral CR Tablets 200-400 mg b.i.d.) as Monotherapy in Subjects With Newly Diagnosed Epilepsy.
• Study Start Date: February 2005
• Actual Primary Completion Date: October 2007
• Actual Study Completion Date: October 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: Levetiracetam; Daily dose of 1000 to 3000 mg film-coated oral tablets, 250-500 mg twice daily.	Drug: Levetiracetam; Daily dose of 1000 to 3000 mg film-coated oral tablets, 250-500 mg twice daily.
Active Comparator: Older Antepileptic Drugs; Older AEDs consist of CBZ-CR 200 mg and 400 mg and VPA-ER 300 mg and 500 mg.	Drug: Carbamazepine Controlled Release (CBZ-CR); Daily dose of 600-1600 mg CR oral tablets, 200 mg and 400 mg twice daily.; Drug: Valproate Extended Release; Daily dose of 1000-2000 mg ER oral tablets, 300 mg and 500 mg twice daily.

Outcome Measures

Primary Outcome Measures :

1. Time to withdrawal from study medication (starting at V1) as a measure of combined efficacy and safety [ Time Frame: Visit 1 to End of Study (approximately 52 weeks) ]

Secondary Outcome Measures :

1. The time to withdrawal comparing Levetiracetam versus the older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release or Sodium Valproate Extended Release [ Time Frame: Visit 1 to End of Study (approximately 52 weeks) ]
2. The retention rate after 6 months comparing Levetiracetam versus the older Antiepileptic Drugs [ Time Frame: Visit 1 to Visit 4 (approximately 26 weeks) ]
3. The retention rate after 12 months comparing Levetiracetam versus the older Antiepileptic Drugs [ Time Frame: Visit 1 to Visit 5 (approximately 52 weeks) ]
4. The retention rate after 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release or Sodium Valproate Extended Release [ Time Frame: Visit 1 to Visit 4 (approximately 26 weeks) ]
5. The retention rate after 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release or Sodium Valproate Extended Release [ Time Frame: Visit 1 to Visit 5 (approximately 52 weeks) ]
6. Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs [ Time Frame: Visit 1 to Visit 4 (approximately 26 weeks) ]
7. Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs [ Time Frame: Visit 1 to Visit 5 (approximately 52 weeks) ]
8. Seizure freedom at 6 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release or Sodium Valproate Extended Release [ Time Frame: Visit 1 to Visit 4 (approximately 26 weeks) ]
9. Seizure freedom at 12 months comparing Levetiracetam versus older Antiepileptic Drugs based on based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release or Sodium Valproate Extended Release [ Time Frame: Visit 1 to Visit 5 (approximately 52 weeks) ]
10. Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs [ Time Frame: Visit 1 to End of Study (approximately 52 weeks) ]
11. Time to first seizure comparing Levetiracetam versus older Antiepileptic Drugs based on the subset of subjects whose best recommended treatment was Carbamazepine Controlled Release or Sodium Valproate Extended Release [ Time Frame: Visit 1 to End of Study (approximately 52 weeks) ]

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of epilepsy (all types of seizures) was made during the past year
• Subjects must have had at least two unprovoked seizures in the past 2 years with at least one during the last 6 months
• Female subjects without childbearing potential are eligible. Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method

Exclusion Criteria:

• Subjects previously allocated to a trial treatment (CBZ, VPA and LEV) used in this trial
• Participation in another clinical trial with an investigational drug or device within 12 weeks of the selection visit (V1), or at any time during this trial
• Pregnant or lactating women
• Presence of known pseudoseizures within the last year
• Uncountable seizures (clusters) or history of convulsive status epilepticus
• Any disorder or condition that may interfere with the absorption, distribution, metabolisation or excretion of drugs
• History of suicide attempt, current suicidal ideation, or other serious psychiatric disorders requiring or having required hospitalization or medication within the previous five years
• Presence of progressive cerebral disease, any other progressively degenerative neurological disease, or any cerebral tumors
• Presence of a terminal illness or any medical condition that might interfere with the subject's trial participation

Contacts and Locations

  Show 231 Study Locations

Sponsors and Collaborators

UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center; UCB Pharma

More Information

Additional Information:

Clinical Study Summary on UCB.com 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pohlmann-Eden B, Marson AG, Noack-Rink M, Ramirez F, Tofighy A, Werhahn KJ, Wild I, Trinka E. Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study. BMC Neurol. 2016 Aug 23;16(1):149. doi: 10.1186/s12883-016-0663-7.

Trinka E, Marson AG, Van Paesschen W, Kälviäinen R, Marovac J, Duncan B, Buyle S, Hallström Y, Hon P, Muscas GC, Newton M, Meencke HJ, Smith PE, Pohlmann-Eden B; KOMET Study Group. KOMET: an unblinded, randomised, two parallel-group, stratified trial comparing the effectiveness of levetiracetam with controlled-release carbamazepine and extended-release sodium valproate as monotherapy in patients with newly diagnosed epilepsy. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1138-47. doi: 10.1136/jnnp-2011-300376. Epub 2012 Aug 29.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00175903 History of Changes
• Other Study ID Numbers: N01175; 2004-001339-41 ( EudraCT Number )
• First Posted: September 15, 2005
• Last Update Posted: March 17, 2015
• Last Verified: March 2015

Keywords provided by UCB Pharma:

Newly Diagnosed Epilepsy; Levetiracetam; Keppra; Carbamazepine; Valproate

Additional relevant MeSH terms:

Carbamazepine; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 Enzyme Inducers; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Levetiracetam; Valproic Acid; Anticonvulsants; Nootropic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; GABA Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Antimanic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Sodium Channel Blockers; Membrane Transport Modulators