The effectiveness of DIACOMIT for the treatment of seizures associated with Dravet syndrome was established in 2 multicenter placebo-controlled double-blind randomized studies (Study 1 and Study 2), conducted according to similar protocols. To be enrolled in either study, patients were required to be 3 years to less than 18 years of age, to have Dravet syndrome (ILAE classification of epilepsy, 1989), and to be inadequately controlled on clobazam and valproate, with at least 4 generalized clonic or tonic-clonic seizures per month despite optimized therapy.

Eligible patients were enrolled in a 1-month baseline period during which they continued to receive their optimized antiepileptic treatment. Following this 1-month baseline, patients were randomly allocated to receive either DIACOMIT (fixed dose of 50 mg/kg/day in divided doses with no dose titration) or placebo, added to their treatment with clobazam and valproate. Duration of double-blind treatment was 2 months. The frequency of generalized clonic or tonic-clonic seizures during the study was recorded by patients and/or their caregivers, using a diary. Although patients with Dravet syndrome have several different types of seizures, only generalized clonic or tonic-clonic seizures were recorded, as other seizure types can be difficult to recognize by patients and/or their caregivers as seizures.

The primary efficacy endpoint for both studies was the responder rate. A responder was defined as a patient who experienced a greater than 50% decrease in the frequency (per 30 days) of generalized clonic or tonic-clonic seizures during the double-blind treatment period compared to the 4-week baseline period (i.e., placebo run-in). The mean change from baseline in frequency of generalized clonic or tonic clonic seizures was also evaluated.

In Study 1 (n=41), 21 patients were randomized to DIACOMIT, and 20 patients to placebo. In Study 2 (n=23), 12 patients were randomized to DIACOMIT, and 11 patients to placebo. In both studies, the demographic and baseline clinical characteristics were similar between the treatment groups.

Table5 summarizes the results of the primary endpoint for DIACOMIT in each study.

In both studies, the responder rate (primary efficacy endpoint) was significantly greater for DIACOMIT than for placebo. DIACOMIT was also superior to placebo for the reduction in mean frequency of generalized clonic or tonic-clonic seizures. In Study 1 and Study 2, respectively 43% and 25% of patients reported no generalized clonic or tonic-clonic seizure for the duration of the study.

Figure 1 displays the percentage of patients by category of percent reduction in tonic-clonic and clonic seizure frequency during month 2 of the treatment period compared to baseline (per 30 days) in Study 1 and Study 2 (pooled).

Figure 1.: Proportion of Patients by Category of Seizure Response for DIACOMIT and Placebo in Study 1 and Study 2 Pooled, Baseline to 2nd Month of Treatment (per 30 days).

The effectiveness of DIACOMIT for the treatment of seizures associated with Dravet syndrome in patients 6 months of age to less than 3 years of age was extrapolated from the demonstration of effectiveness in patients 3 years to less than 18 years of age in Study 1 and Study 2.