PMID- 26393492
OWN - NLM
STAT- MEDLINE
DCOM- 20160608
LR  - 20151117
IS  - 1744-764X (Electronic)
IS  - 1474-0338 (Linking)
VI  - 14
IP  - 11
DP  - 2015
TI  - Safety profile of tasimelteon, a melatonin MT1 and MT2 receptor agonist: pooled 
      safety analyses from six clinical studies.
PG  - 1673-85
LID - 10.1517/14740338.2015.1093112 [doi]
AB  - INTRODUCTION: Tasimelteon, a novel circadian regulator, is the first product for 
      the treatment of Non-24-hour Sleep-Wake Disorder (Non-24) approved by either the 
      FDA or the European Medicines Agency (EMA). Tasimelteon is a potent and specific 
      melatonin (MT1 and MT2) receptor agonist with 2 - 4 times greater affinity for 
      the MT2 receptor. METHODS: Safety was assessed in two controlled and two 
      open-label studies in blind individuals with Non-24 and in two controlled studies 
      of primary insomnia. Periodic assessments included collection of adverse events 
      (AEs), laboratory testing, electrocardiograms (ECGs), vital sign monitoring, 
      physical examinations and assessment for the potential for suicide. One study 
      included additional assessments for endocrine function. RESULTS: A total of 184 
      blind individuals with Non-24 received tasimelteon nightly with a median exposure 
      > 1 year. In placebo-controlled studies, 387 patients with insomnia and 42 
      patients with Non-24 received tasimelteon nightly for 4 - 26 weeks. The total 
      patient years exposure for the six studies assessed here is 258.64 patient years. 
      Discontinuations due to AEs were similar across treatment groups. Overall in the 
      clinical studies described here, AEs attributable to tasimelteon treatment were 
      headache, diarrhea, dry mouth, alanine aminotransferase increased, somnolence, 
      dizziness and nightmare/abnormal dreams. There were no clinically significant 
      differences in treatment group with ECGs, vital signs, withdrawal, endocrine 
      function and suicidality assessments. CONCLUSION: Long-term tasimelteon 
      administration was safe and well-tolerated. This is supported by 
      placebo-controlled data in both Non-24 and insomnia patients.
FAU - Leger, Damien
AU  - Leger D
AD  - a 1 Universite Paris Descartes, APHP, Hotel-Dieu de Paris, Centre du Sommeil et 
      de la Vigilance , 1 place du Parvis Notre Dame, 75181 Paris cedex 04, Paris, 
      France +33 1 42 34 82 43 ; +33 1 42 34 82 27 ; damien.leger@htd.aphp.fr.
AD  - b 2 Universite Paris Descartes, EA 7330 VIFASOM Sommeil-Vigilance-Fatigue et 
      Sante Publique , Paris, France.
FAU - Quera-Salva, Maria-Antonia
AU  - Quera-Salva MA
AD  - c 3 APHP, Hopital Raymond Poincare, Unite de sommeil , Garches, France.
FAU - Vecchierini, Marie-Francoise
AU  - Vecchierini MF
AD  - a 1 Universite Paris Descartes, APHP, Hotel-Dieu de Paris, Centre du Sommeil et 
      de la Vigilance , 1 place du Parvis Notre Dame, 75181 Paris cedex 04, Paris, 
      France +33 1 42 34 82 43 ; +33 1 42 34 82 27 ; damien.leger@htd.aphp.fr.
AD  - b 2 Universite Paris Descartes, EA 7330 VIFASOM Sommeil-Vigilance-Fatigue et 
      Sante Publique , Paris, France.
FAU - Ogrizek, Pascale
AU  - Ogrizek P
AD  - a 1 Universite Paris Descartes, APHP, Hotel-Dieu de Paris, Centre du Sommeil et 
      de la Vigilance , 1 place du Parvis Notre Dame, 75181 Paris cedex 04, Paris, 
      France +33 1 42 34 82 43 ; +33 1 42 34 82 27 ; damien.leger@htd.aphp.fr.
FAU - Perry, Christina A
AU  - Perry CA
AD  - d 4 Vanda Pharmaceuticals , Washington, DC, USA.
FAU - Dressman, Marlene A
AU  - Dressman MA
AD  - d 4 Vanda Pharmaceuticals , Washington, DC, USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20150922
PL  - England
TA  - Expert Opin Drug Saf
JT  - Expert opinion on drug safety
JID - 101163027
RN  - 0 (Benzofurans)
RN  - 0 (Cyclopropanes)
RN  - 0 (Receptor, Melatonin, MT1)
RN  - 0 (Receptor, Melatonin, MT2)
RN  - SHS4PU80D9 (tasimelteon)
SB  - IM
MH  - Benzofurans/administration & dosage/*adverse effects/pharmacology
MH  - Cyclopropanes/administration & dosage/*adverse effects/pharmacology
MH  - Humans
MH  - Receptor, Melatonin, MT1/*agonists
MH  - Receptor, Melatonin, MT2/*agonists
MH  - Sleep Disorders, Circadian Rhythm/drug therapy
MH  - Sleep Initiation and Maintenance Disorders/drug therapy
MH  - Time Factors
OTO - NOTNLM
OT  - blindness
OT  - circadian
OT  - melatonin receptor agonist
OT  - non-24-h sleep-wake disorder
OT  - safety
OT  - tasimelteon
EDAT- 2015/09/24 06:00
MHDA- 2016/06/09 06:00
CRDT- 2015/09/23 06:00
PHST- 2015/09/23 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
AID - 10.1517/14740338.2015.1093112 [doi]
PST - ppublish
SO  - Expert Opin Drug Saf. 2015;14(11):1673-85. doi: 10.1517/14740338.2015.1093112. 
      Epub 2015 Sep 22.