PMID- 30357823
OWN - NLM
STAT- MEDLINE
DCOM- 20190404
LR  - 20190404
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 59
IP  - 11
DP  - 2018 Nov
TI  - Pharmacokinetics of clobazam oral soluble film.
PG  - 2153-2161
LID - 10.1111/epi.14581 [doi]
AB  - OBJECTIVE: Clobazam oral soluble film (COSF) is a novel dosage form under 
      development for the adjunctive treatment of seizures associated with 
      Lennox-Gastaut syndrome. The present study was undertaken to assess the 
      pharmacokinetics of clobazam administered as single doses of COSF 20 and 10 mg 
      compared with clobazam tablets (CTAB) 20 and 10 mg in healthy adults. A secondary 
      objective was to assess the safety and tolerability of single doses of COSF 20 
      and 10 mg. METHODS: A total of 51 adult volunteers were enrolled in a 
      single-dose, open-label, randomized four-sequence, four-period, crossover study 
      with treatments (A) COSF 20 mg, (B) CTAB 20 mg, (C) COSF 10 mg, and (D) CTAB 10 
      mg. Pharmacokinetic sampling for clobazam and N-desmethylclobazam was carried out 
      until 21 days postdose with a 28-day washout. Subjects were monitored for adverse 
      events (AEs) throughout the study. Visual inspections of the administration site 
      were performed before and after COSF administration to monitor for mucosal 
      irritation. RESULTS: COSF at single doses of 10 and 20 mg was bioequivalent to 
      CTAB at equivalent doses for both clobazam and its active metabolite 
      N-desmethylclobazam. The pharmacokinetics of both formulations was 
      dose-proportional at doses of 10 and 20 mg. The number of AEs and the number of 
      subjects experiencing AEs were dose-related across the treatment groups, with 
      somnolence the most common event. None of these events was severe or serious, and 
      most were mild. There was no evidence for local irritation at the administration 
      site following COSF. SIGNIFICANCE: COSF is a novel clobazam dosage form that is 
      bioequivalent to CTAB. Because of its ease of administration, COSF may be 
      expected to improve adherence, reduce likelihood of dosing error, and provide 
      more accurate dosing than formulations of clobazam that are currently available.
CI  - (c) 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of 
      International League Against Epilepsy.
FAU - Heller, Allen H
AU  - Heller AH
AD  - Pharma Study Design LLC, Woodbridge, Connecticut.
FAU - Wargacki, Stephen
AU  - Wargacki S
AD  - Aquestive Therapeutics, Inc, Warren, New Jersey.
FAU - Jung, Cassie
AU  - Jung C
AD  - Aquestive Therapeutics, Inc, Warren, New Jersey.
FAU - Buan, Carla V
AU  - Buan CV
AD  - Aquestive Therapeutics, Inc, Warren, New Jersey.
FAU - Wyatt, David J
AU  - Wyatt DJ
AD  - Syneos Health Clinical Solutions, Early Phase, Miami, Florida.
FAU - Schobel, A Mark
AU  - Schobel AM
AD  - Aquestive Therapeutics, Inc, Warren, New Jersey.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181024
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 2MRO291B4U (Clobazam)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Anticonvulsants/*pharmacokinetics
MH  - Area Under Curve
MH  - Clobazam/*pharmacokinetics
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Drug Delivery Systems/*methods
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Single-Blind Method
MH  - Therapeutic Equivalency
MH  - Young Adult
OTO - NOTNLM
OT  - Lennox-Gastaut
OT  - N-desmethylclobazam
OT  - anticonvulsants
OT  - antiepileptics
OT  - bioequivalence
EDAT- 2018/10/26 06:00
MHDA- 2019/04/05 06:00
CRDT- 2018/10/26 06:00
PHST- 2018/06/29 00:00 [received]
PHST- 2018/09/21 00:00 [revised]
PHST- 2018/09/21 00:00 [accepted]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2019/04/05 06:00 [medline]
PHST- 2018/10/26 06:00 [entrez]
AID - 10.1111/epi.14581 [doi]
PST - ppublish
SO  - Epilepsia. 2018 Nov;59(11):2153-2161. doi: 10.1111/epi.14581. Epub 2018 Oct 24.