Keppra Phase IV study - favourable
First results from UCB Pharma's ongoing Phase IV SKATE (Safety of Keppra as Adjunctive Therapy in Epilepsy) study shows favourable rates of efficacy for Keppra (levetiracetam) in a broad population of difficult to treat patients. Phase IV studies are considered to be closer to clinical practice and specifically further explores the safety of a treatment that has been registered for a particular indication. In this case the results of the SKATE study, similarly to the Keeper study (the US equivalent Phase IV trial), show a high proportion of patients with partial onset seizures experienced an overall significant clinical improvement when treated with Keppra. The SKATE study showed that seizure frequency was reduced by half or more in 49% of patients1. This efficacy was confirmed across different partial seizure types1 and in addition, the results also showed a substantial seizure freedom rate of 17.2% over the entire study duration (sixteen weeks). It makes Keppra a good candidate for possibly becoming a first-choice add-on antiepileptic drug (AED).
The interim results were based on data from 731 patients recruited from nine countries; Belgium, Czech Republic, Germany, Finland, France, Netherlands, Switzerland, UK and Argentina with 117 investigators.
SKATE study design
The SKATE trial is a Phase IV, open-label, multi-centre trial studying the safety and efficacy of Keppra as an adjunctive therapy in adult patients with uncontrolled partial seizures, which began in April 2000. The interim results were based on a 16-week treatment period in a broad population of refractory patients, with between one and fourteen partial-onset seizures per month, averaged over the three month-period preceding the selection visit.
Study results
Patient demographics
The mean age of patients involved in the SKATE study was 38.4 years and the mean duration of time the patients had been diagnosed with epilepsy was 21 years, with a median baseline partial seizure frequency of four seizures per month. Out of the 731 patients in the study, most patients could be diagnosed as highly refractory - with two thirds of patients having tried a treatment and failed with 3 or more AEDs prior to study entry - and were still uncontrolled; the majority of patients (67%) entered the study on two or more concomitant AEDs.
High retention
Overall the results showed a retention rate for Keppra with 84.4% of patients having completed the study, which is considered very high.
Efficacy
The SKATE results showed favourable efficacy in controlling partial seizures with seizure frequencies reduced by half or more in 49% of patients (353/720) as well as a seizure freedom rate of 17.2% over the whole study period. Keppra was also effective in the different subtypes of partial seizure. In simple partial seizures 36.6% of patients (90/246) experienced a reduction in seizures greater or equal to 50% and 17.9% were completely seizure free. While 49.8% of patients (286/574) with complex partial seizures experienced a reduction in seizures greater or equal to 50% and 20.9% were completely seizure free.
In addition, 65% of patients (167/257) with secondarily generalised tonic-clonic seizures experienced a reduction in seizures greater or equal to 50%, and nearly half (46.3%) were completely seizure free.
Safety
The adverse event profile was consistent with that seen in the Phase III clinical development program, with the four most commonly reported adverse events leading to discontinuation as follows; somnolence (2.2%), asthenia (fatigue) (1.8%), convulsions (1.8%), headache (1.4%) and dizziness (1.4%)1. Overall, the most common adverse events were predominantly mild to moderate in severity and rarely led to discontinuation (8.6%).
Commenting on the significance of the study, Professor Christian Elger, Klinik fuer Epileptologie, University of Bonn, commented: 'The SKATE study clearly shows that Keppra offers unparalleled efficacy in terms of seizure control and seizure freedom rates across several partial seizure types, but also an unmatched tolerability profile. The SKATE study provides data that supports Keppra in the therapeutic armamentarium by identifying this newer antiepileptic as an optimal first choice add-on therapy.
'Given Keppra's efficacy in the SKATE study, I am sure that clinicians around the world will be interested in the final results of SKATE - and indeed in results of ongoing trials including those looking at Keppra in monotherapy, in primary generalised seizures and in children.'
UCB global medical manager CNS, Dr Peter Verdu commented: 'We are pleased that these results confirm the phase III trials that allowed the registration of Keppra and are entirely in line with the results from KEEPER, the phase IV study conducted in the US. It has encouraged us at UCB Pharma to continue our commitment to investing in clinical research that may lead to the improvement of the quality of life of people with epilepsy.'