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

Joanne Rogin, James Wheless, Bassel Abou-Khalil, Kevin D. Wolter, Glenn C. Pixton, Nancy A. Sherman, Rajesh B. Shukla, Carl L. Roland, Kenneth W. Sommerville

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 openlabel 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 injectionsite bruising (6.3%). Although three subjects met the predefined respiratory rate threshold, none were considered clinically significant or reported as AEs.

Significance: Long-term treatment with diazepam AI administered by trained caregivers in an outpatient setting to treat ARS is a safe and effective option.

Original languageEnglish (US)
Pages (from-to)1444-1451
Number of pages8
JournalEpilepsia
Volume55
Issue number9
DOIs
StatePublished - Jan 1 2014

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Diazepam
Caregivers
Seizures
Outpatients
Safety
Therapeutics
Hospital Emergency Service
Placebos
Injections
Respiratory Rate
Multicenter Studies
Respiration
Hemorrhage
Pain

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

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. / Rogin, Joanne; Wheless, James; Abou-Khalil, Bassel; Wolter, Kevin D.; Pixton, Glenn C.; Sherman, Nancy A.; Shukla, Rajesh B.; Roland, Carl L.; Sommerville, Kenneth W.

In: Epilepsia, Vol. 55, No. 9, 01.01.2014, p. 1444-1451.

Research output: Contribution to journalArticle

Rogin, Joanne ; Wheless, James ; Abou-Khalil, Bassel ; Wolter, Kevin D. ; Pixton, Glenn C. ; Sherman, Nancy A. ; Shukla, Rajesh B. ; Roland, Carl L. ; Sommerville, Kenneth W. / 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. In: Epilepsia. 2014 ; Vol. 55, No. 9. pp. 1444-1451.
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AU - Abou-Khalil, Bassel

AU - Wolter, Kevin D.

AU - Pixton, Glenn C.

AU - Sherman, Nancy A.

AU - Shukla, Rajesh B.

AU - Roland, Carl L.

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N2 - 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 openlabel 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 injectionsite bruising (6.3%). Although three subjects met the predefined respiratory rate threshold, none were considered clinically significant or reported as AEs.Significance: Long-term treatment with diazepam AI administered by trained caregivers in an outpatient setting to treat ARS is a safe and effective option.

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