The effectiveness of diazepam rectal gel has been established in two adequate and well controlled clinical studies in children and adults exhibiting the seizure pattern described below under INDICATIONS AND USAGE.

A randomized, double-blind study compared sequential doses of diazepam rectal gel and placebo in 91 patients (47 children, 44 adults) exhibiting the appropriate seizure profile. The first dose was given at the onset of an identified episode. Children were dosed again four hours after the first dose and were observed for a total of 12 hours. Adults were dosed at four and 12 hours after the first dose and were observed for a total of 24 hours. Primary outcomes for this study were seizure frequency during the period of observation and a global assessment that took into account the severity and nature of the seizures as well as their frequency.

The median seizure frequency for the diazepam rectal gel treated group was zero seizures per hour, compared to a median seizure frequency of 0.3 seizures per hour for the placebo group, a difference that was statistically significant (p <0.0001). All three categories of the global assessment (seizure frequency, seizure severity, and "overall") were also found to be statistically significant in favor of diazepam rectal gel (p < 0.0001). The following histogram displays the results for the "overall" category of the global assessment.

FIGURE 2: Caregiver Overall Global Assessment of the Efficacy of Diazepam Rectal Gel 

Patients treated with diazepam rectal gel experienced prolonged time-to-next-seizure compared to placebo (p = 0.0002) as shown in the following graph.

FIGURE 3: Kaplan- Meier Survival Analysis of Time- to- Next- Seizure – First Study

In addition, 62% of patients treated with diazepam rectal gel were seizure-free during the observation period compared to 20% of placebo patients.

Analysis of response by gender and age revealed no substantial differences between treatment in either of these subgroups. Analysis of response by race was considered unreliable, due to the small percentage of non-Caucasians.

A second double-blind study compared single doses of diazepam rectal gel and placebo in 114 patients (53 children, 61 adults). The dose was given at the onset of the identified episode and patients were observed for a total of 12 hours. The primary outcome in this study was seizure frequency. The median seizure frequency for the diazepam rectal gel-treated group was zero seizures per 12 hours, compared to a median seizure frequency of 2.0 seizures per 12 hours for the placebo group, a difference that was statistically significant (p < 0.03). Patients treated with diazepam rectal gel experienced prolonged time- to-next-seizure compared to placebo (p = 0.0072) as shown in the following graph.

FIGURE 4: Kaplan- Meier Survival Analysis of Time- to- Next- Seizure – Second Study

In addition, 55% of patients treated with diazepam rectal gel were seizure-free during the observation period compared to 34% of patients receiving placebo. Overall, caregivers judged diazepam rectal gel to be more effective than placebo (p = 0.018), based on a 10 centimeter visual analog scale. In addition, investigators also evaluated the effectiveness of diazepam rectal gel and judged diazepam rectal gel to be more effective than placebo (p < 0.001).

An analysis of response by gender revealed a statistically significant difference between treatments in females but not in males in this study, and the difference between the 2 genders in response to the treatments reached borderline statistical significance. Analysis of response by race was considered unreliable, due to the small percentage of non-Caucasians.