title: Safety and effectiveness of long-term treatment with diazepam auto-injector administered by caregivers in an outpatient setting for the treatment of acute repetitive seizures.
abstract: OBJECTIVE
  Part 1 of this phase III study was a randomized, double-blind, parallel-group, placebo-controlled, multicenter study of caregiver administered diazepam auto-injector (AI) in subjects with acute repetitive seizures (ARS) and demonstrated that diazepam AI was well-tolerated and significantly more effective than placebo AI in delaying the time to next seizure or rescue. Part 2 of this study, presented herein, was an open-label continuation to assess the long-term safety and effectiveness of diazepam AI for the treatment of ARS.
  
  
  METHODS
  Of the 234 subjects randomized in part 1, 161 continued into part 2 and were provided open-label diazepam AI. Effectiveness measures were time to next seizure or rescue, number of subsequent rescues by type (rescue medication, emergency room visit, or other medical care), and number of subsequent seizures during the 12-h follow-up period. Safety data (adverse events and respirations <8/min) were also collected.
  
  
  RESULTS
  During the open-label part 2 study, 129 subjects were administered a total of 1,380 diazepam AI treatments (median 4.5; range 1-118), of which 1,071 (77.6%) were effective with no subsequent seizure or rescue during the 12-h follow-up period. Median number of subsequent seizures experienced by subjects was one (range 0-20). Of the 1,380 administrations, 79 (5.7%) required use of rescue medication, 18 (1.3%) required a visit to an emergency room, and 6 (0.4%) required other rescue medical care. In most (75%) of subjects with treatment-emergent adverse events (TEAEs), TEAEs were mild or moderate in severity. Commonly reported treatment-related TEAEs were injection-site pain (10.9%), injection-site hemorrhage (7%), and injection-site bruising (6.3%). Although three subjects met the predefined respiratory rate threshold, none were considered clinically significant or reported as AEs.
  
  
  CONCLUSIONS
  Long-term treatment with diazepam AI administered by trained caregivers in an outpatient setting to treat ARS is a safe and effective option. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
authors: Minneapolis Clinic of Neurology, Midwest Center for Seizure Disorders, Golden Valley, Minnesota, U.S.A.
authors: Joanne
authors: J
authors: Rogin
authors: James
authors: J
authors: Wheless
authors: Bassel
authors: B
authors: Abou-Khalil
authors: Kevin D
authors: KD
authors: Wolter
authors: Glenn C
authors: GC
authors: Pixton
authors: Nancy A
authors: NA
authors: Sherman
authors: Rajesh B
authors: RB
authors: Shukla
authors: Carl L
authors: CL
authors: Roland
authors: Kenneth W
authors: KW
authors: Sommerville
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage*; D017028:Caregivers / Q000523:psychology; D002648:Child; D003975:Diazepam / Q000008:administration & dosage*; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010045:Outpatients; D012640:Seizures / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D003975:Diazepam
keywords: Autoinjection; Benzodiazepines; Clinical trial; Cluster seizures; Serial seizures