title: Single therapeutic and supratherapeutic doses of laropiprant, a selective prostaglandin D2 receptor 1 antagonist, do not prolong the QTcF interval in healthy volunteers.
abstract: Laropiprant (LRPT), a prostaglandin D(2) receptor-1 antagonist shown to reduce niacin-induced flushing symptoms, has been combined with niacin for treatment of dyslipidemia. This study evaluated the effects of LRPT (50 mg and 600 mg, respectively) on the QT interval with Fridericia's correction (QTcF). QTcF measurements were made over a 24-hour period following administration of single-dose moxifloxacin 400 mg, LRPT 50 mg, LRPT 600 mg, or placebo. The primary hypothesis was supported if the 90% confidence intervals (CIs) for the least squares (LS) mean differences between placebo and LRPT in change from baseline in QTcF interval were <10 milliseconds at every time point. The upper limits of the 90% CIs for LS mean differences from placebo in changes from baseline in QTcF intervals for LRPT 50 mg and 600 mg were <5 milliseconds at every time point. The lower limits of the 90% CIs for placebo-adjusted LS mean changes from baseline in QTcF intervals for moxifloxacin exceeded 0 milliseconds at every time point, demonstrating the sensitivity of this assay to detect increases in the QTcF interval. In conclusion, single doses of LRPT 50 mg and 600 mg do not prolong the QTcF interval relative to placebo and are generally well tolerated.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey, USA.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Luo
authors.forename: Tami
authors.initials: T
authors.lastname: Crumley
authors.forename: David
authors.initials: D
authors.lastname: Ebel
authors.forename: George J
authors.initials: GJ
authors.lastname: Atiee
authors.forename: Jane
authors.initials: J
authors.lastname: Royalty
authors.forename: Amy O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.forename: John
authors.initials: J
authors.lastname: Wagner
authors.forename: Eseng
authors.initials: E
authors.lastname: Lai
mesh_terms: D000293:Adolescent; D000328:Adult; D001372:Aza Compounds / Q000009:adverse effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000009:adverse effects*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D007211:Indoles; C518174:MK-0524; D011804:Quinolines; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000077266:Moxifloxacin; C036293:prostaglandin D2 receptor