title: Safety profile of tasimelteon, a melatonin MT1 and MT2 receptor agonist: pooled safety analyses from six clinical studies.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  Long-term tasimelteon administration was safe and well-tolerated. This is supported by placebo-controlled data in both Non-24 and insomnia patients.
authors.affiliation: a 1 Université Paris Descartes, APHP, Hôtel-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.|b 2 Université Paris Descartes, EA 7330 VIFASOM Sommeil-Vigilance-Fatigue et Santé Publique , Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Leger
authors.affiliation: c 3 APHP, Hôpital Raymond Poincaré, Unité de sommeil , Garches, France.
authors.forename: Maria-Antonia
authors.initials: MA
authors.lastname: Quera-Salva
authors.affiliation: a 1 Université Paris Descartes, APHP, Hôtel-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.|b 2 Université Paris Descartes, EA 7330 VIFASOM Sommeil-Vigilance-Fatigue et Santé Publique , Paris, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Vecchierini
authors.affiliation: a 1 Université Paris Descartes, APHP, Hôtel-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.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ogrizek
authors.affiliation: d 4 Vanda Pharmaceuticals , Washington, DC, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Perry
authors.affiliation: d 4 Vanda Pharmaceuticals , Washington, DC, USA.
authors.forename: Marlene A
authors.initials: MA
authors.lastname: Dressman
mesh_terms: D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D003521:Cyclopropanes / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D044122:Receptor, Melatonin, MT1 / Q000819:agonists*; D044123:Receptor, Melatonin, MT2 / Q000819:agonists*; D020178:Sleep Disorders, Circadian Rhythm / Q000188:drug therapy; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy; D013997:Time Factors
chemical_list: D001572:Benzofurans; D003521:Cyclopropanes; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; C478745:tasimelteon
keywords: blindness; circadian; melatonin receptor agonist; non-24-h sleep-wake disorder; safety; tasimelteon