PMID- 34307747
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220514
IS  - 2330-1619 (Electronic)
IS  - 2330-1619 (Linking)
VI  - 8
IP  - 5
DP  - 2021 Jul
TI  - An Open-Label Phase 2a Study to Evaluate the Safety and Tolerability of 
      Perampanel in Cervical Dystonia.
PG  - 743-749
LID - 10.1002/mdc3.13229 [doi]
AB  - BACKGROUND: Cervical dystonia (CD) is the most common focal isolated dystonia. 
      Preclinical studies report that AMPA-selective glutamate receptor antagonists 
      improve dystonia. Perampanel is a clinically available, AMPA receptor antagonist 
      that has shown efficacy and safety in epilepsy. OBJECTIVES: To determine safety 
      and tolerability of perampanel in CD. METHODS: We performed a phase 2a, 
      open-label, multicenter study to evaluate tolerability and safety of perampanel 
      in CD. Included subjects had primary CD; those on botulinum toxin were 8 weeks 
      post last injection. All subjects received perampanel 2 mg/day, titrated 2 mg 
      weekly over 6 weeks, to maximum 12 mg/day; maintenance phase was 4 weeks, ending 
      at week 10. Primary endpoints included tolerability, defined as ability to remain 
      on perampanel for the maintenance period, at any dose level and safety, 
      determined from adverse events (AEs) collected at each visit. Secondary 
      exploratory endpoints included Toronto Western Spasmodic Torticollis Rating Scale 
      (TWSTRS), quality of life (cervical dystonia impact profile [CIDP]-58) and 
      Clinical Global Impression of change (CGI). RESULTS: CD participants (n = 25) 
      were recruited. Eight subjects withdrew; 4 because of AEs, 3 for other reasons 
      and 1 lost to follow up. One subject tolerated 12 mg/day. Eight subjects (30.8%) 
      tolerated 2 mg, whereas 19.2% tolerated 4 mg/day, and 15.4% tolerated 6 mg or 
      8 mg/day. All subjects experienced AEs. The most common AEs were dizziness, 
      imbalance, and irritability. Exploratory endpoints of TWSTRS showed some improved 
      pain scores and CIDP-58 improved sleep. CONCLUSIONS: Tolerability to perampanel 
      was variable in CD subjects. Lower doses would be considered for future studies 
      in this population.
CI  - (c) 2021 International Parkinson and Movement Disorder Society.
FAU - Fox, Susan H
AU  - Fox SH
AD  - The Edmond J Safra Program in Parkinson Disease, Toronto Western Hospital Toronto 
      Ontario Canada.
AD  - Krembil Brain Institute, University Health Network Toronto Ontario Canada.
AD  - Division of Neurology University of Toronto Toronto Ontario Canada.
FAU - Swan, Matthew
AU  - Swan M
AD  - Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai New York New 
      York USA.
FAU - Jinnah, Hyder A
AU  - Jinnah HA
AD  - Department of Human Genetics and Pediatrics Emory University Atlanta Georgia USA.
FAU - de Freitas, Maria E T
AU  - de Freitas MET
AD  - The Edmond J Safra Program in Parkinson Disease, Toronto Western Hospital Toronto 
      Ontario Canada.
AD  - Krembil Brain Institute, University Health Network Toronto Ontario Canada.
AD  - Division of Neurology University of Toronto Toronto Ontario Canada.
FAU - de Oliveira, Lais M
AU  - de Oliveira LM
AD  - The Edmond J Safra Program in Parkinson Disease, Toronto Western Hospital Toronto 
      Ontario Canada.
AD  - Krembil Brain Institute, University Health Network Toronto Ontario Canada.
AD  - Division of Neurology University of Toronto Toronto Ontario Canada.
FAU - Al-Shorafat, Duha
AU  - Al-Shorafat D
AD  - The Edmond J Safra Program in Parkinson Disease, Toronto Western Hospital Toronto 
      Ontario Canada.
AD  - Krembil Brain Institute, University Health Network Toronto Ontario Canada.
AD  - Division of Neurology University of Toronto Toronto Ontario Canada.
FAU - Fernandez, Hubert H
AU  - Fernandez HH
AD  - Cleveland Clinic Cleveland Ohio USA.
FAU - Kompoliti, Katie
AU  - Kompoliti K
AD  - Rush University Medical Centre Chicago Illinois USA.
FAU - Comella, Cynthia
AU  - Comella C
AD  - Rush University Medical Centre Chicago Illinois USA.
LA  - eng
PT  - Journal Article
DEP - 20210513
PL  - United States
TA  - Mov Disord Clin Pract
JT  - Movement disorders clinical practice
JID - 101630279
PMC - PMC8287187
OTO - NOTNLM
OT  - AMPA antagonist
OT  - TWSTRS
OT  - cervical dystonia
OT  - clinical trial
OT  - perampanel
COIS- The authors declare that partial funding for this study was provided by Eisai 
      Pharmaceuticals as an Investigator Initiated Trial. Partial funding was from 
      Toronto Western and General Foundation (S.H.F.). The authors have no other 
      conflicts of interest to report.
EDAT- 2021/07/27 06:00
MHDA- 2021/07/27 06:01
PMCR- 2022/05/13
CRDT- 2021/07/26 06:41
PHST- 2021/03/02 00:00 [received]
PHST- 2021/04/14 00:00 [revised]
PHST- 2021/04/20 00:00 [accepted]
PHST- 2021/07/26 06:41 [entrez]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/07/27 06:01 [medline]
PHST- 2022/05/13 00:00 [pmc-release]
AID - MDC313229 [pii]
AID - 10.1002/mdc3.13229 [doi]
PST - epublish
SO  - Mov Disord Clin Pract. 2021 May 13;8(5):743-749. doi: 10.1002/mdc3.13229. 
      eCollection 2021 Jul.