ty was assessed in 292 patients who, in the absence of a seizure, received two 5 mgdoses of NAYZILAM (10 mg total dosage) separated by 10 minutes. Patients were excludedfrom participation in the Comparative Phase if they failed to meet pre-defined blood pressure,heart rate, sedation, electrocardiogram, and peripheral oxygen saturation criteria.
In the Comparative Phase, 201 patients treated a single seizure cluster episode in anoutpatient setting with either a blinded dose of NAYZILAM 5 mg (134 patients) or placebo(67 patients). If the seizure activity persisted or recurred, patients in both groups had theoption to receive a subsequent unblinded dose of NAYZILAM 5 mg to be used between 10minutes and 6 hours after administration of the initial blinded dose of study drug.
The primary efficacy endpoint for Study 1 was treatment success, defined as the terminationof seizures within 10 minutes after the initial blinded dose of study drug and the absence of arecurrence of seizures within 6 hours of the initial blinded dose of study drug. A statisticallysignificantly higher percentage of NAYZILAM-treated patients met the primary efficacyendpoint, as shown in Table 4.
Table 4: Primary Endpoint Results: Treatment Success (Study 1)
NAYZILAM
(N=134)
Placebo
(N=67)
Treatment success (%) 53.7 34.3
95% CI (45.3, 62.2) (23.0, 45.7)
p-value 0.011
Numerical differences in favor of NAYZILAM were observed on each of the components ofthe treatment success responder definition; termination of seizure(s) within 10 minutes afterinitial dose of study drug (80.6 versus 70.1%) and the absence of seizure recurrence between10 minutes and 6 hours after the initial dose of study drug (58.2 versus 37.3%).
Study 1 also eva luated the occurrence and time to next seizure after the initial blinded dose ofstudy drug. A smaller proportion of NAYZILAM-treated patients experienced the nextseizure within 24 hours after the initial blinded dose of study drug (37.3% versus 46.3%).
NAYZILAM-treated patients experienced a statistically longer time-to-next-seizure than theplacebo group (Figure 1).
FIGURE 1: Kaplan-Meier Analysis of Time-to-Next-Seizure (Study 1)
Analysis by gender revealed no substantial differences in treatment response. Informativesubgroup analyses by age and race were not possible because of the small percentage ofpatients less than 18 years of age or 65 years of age or greater, and of non-White patients inthe study.
16 HOW SUPPLIED / STORAGE AND HANDLING
16.1 How Supplied
NAYZILAM is supplied as a solution of midazolam. Each single-dose nasal spray unitdelivers 5 mg of midazolam in 0.1 mL of solution.
NAYZILAM is supplied in boxes of 2 nasal spray units (NDC 50474-500-15), each
contained within an individual blister pack.
16.2 Storage and Handling
Do not open the blister packaging until ready to use. Do not test or prime before use.
Do not use if the nasal spray unit appears damaged.
Store at controlled room temperature 20°C to 25°C (68°F to 77°F). Excursions permitted to15°C to 30°C (59°F to 86°F).
17 PATIENT COUNSELING INFORMATION
Advise patients and caregivers to read the FDA-approved patient labeling (Medication Guideand Instructions for Use).
Risks from Concomitant Use with Opioids
Inform patients and caregivers that potentially fatal additive effects may occur ifNAYZILAM is used with opioids and not to use NAYZILAM concomitantly with opioids
unless supervised by a healthcare provider. If |
