Abstracts

An autoinjector delivery system for intramuscular (i.m.) administration of diazepam (Vanquix[trade] Auto-Injector) is being developed as an alternative to diazepam rectal administration, the only current treatment that can be administered by non-health care professionals for management of patients with acute repetitive seizures (ARS)., The study was conducted as a 2-part, randomized, open-label, single-dose, crossover design in healthy young (ages 18-40 years) adult volunteers. Part I of the study evaluated the pharmacokinetics (PK) of Vanquix[trade] 5, and 15 mg administered i.m. into the mid outer thigh. Part II evaluated the relative bioavailability of Vanquix[trade] 10 mg compared with diazepam rectal gel (Diastat^[reg]) 10 mg administered according to the product label. Serial sampling of plasma, vital signs, and adverse event assessments were done a specified times. Treatments were separated by a 2-week washout period., A total of 48 subjects were enrolled in the study, 24 in each part. In Part I of the study, administration of Vanquix[trade] 5, 10, and 15 mg i.m. resulted in a proportional increase of the diazepam C[sub]max[/sub] and AUC, and a consistent T[sub]max [/sub] of 1.0 hour at each dose level. In Part II of the study, i.m. administration of Vanquix[trade] 10 mg resulted in plasma concentrations of both the diazepam and desmethyldiazepam that were slightly higher and less variable than those observed following diazepam rectal gel 10 mg. Two subjects had negligible absorption of diazepam from the rectal route of administration, which skewed the PK results for the reference drug. Excluding the tow outliers, the geometric mean ratio ( Vanquix[trade] Auto-Injector/Diastat^[reg]) and 90% CIs for diazepam C[sub]max[/sub] and AUC[sub](O-t) [/sub]were 0.94 [0.84, 1.05] and 1.14 [1.08, 1.21], respectively, indicating that the overal bioavailability of Vanquix[trade] was approximately 14% higher than that of diazepam rectal gel (Diastat^[reg]). Both treatments were generally safe and well-tolerated. Although the incidence of treatment-emergent AEs was higher with Vanquix[trade] Auto-Injector compared with Diastat^[reg] (21.7% [italic]versus[/italic] 13.6%), the difference could be attributed to injection site pain. Injection site pain also correlated with the Vanquix[trade] dose administered in Part I: 5 mg (4.3%), 10 mg (21.7%), and 15 mg (27.3%). No other AEs correlated with dose, and there was no evidence of respiratory depression with either drug., The results of this study demonstrate that diazepam can be safely and reliably delivered to the systematic circulation using Vanquix[trade] Auto Injector. The slight (14%) difference in bioavailability between Vanquix[trade] Auto Injector and diazepam rectal gel is of questionable clinical importance and suggests that the two dosage forms could be interchanged on a mg per mg basis., (Supported by King Pharmaceuticals, Inc.)