title: Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy.
abstract: Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting mothers. In April 2013 the FDA approved the delayed-release combination of doxylamine succinate and pyridoxine hydrochloride (Diclegis®) for NVP, based in part, on the results of a phase III randomized trial demonstrating the efficacy of this drug combination [study drug marketed under the trade name Diclectin® in Canada and Diclegis® in the United States] compared to placebo in pregnant women. Study drug dosing occurred for 14 days, which is substantially longer than what has been performed in similar studies. The objective of this study was to evaluate, through secondary analysis, whether the primary measure of efficacy can be demonstrated after five days of treatment.
  
  
  
  Women suffering from NVP were randomized to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from two to four tablets a day, based on a pre-specified titration protocol. The primary efficacy endpoint was the change in the validated Pregnancy-Unique Quantification of Emesis (PUQE) score at baseline versus Day 15 between Diclegis®-treated and placebo-treated women. For the present study, the change in PUQE score between baseline and Day 15 (end of the study) was compared to the changes observed for Days 3, 4, and 5.
  
  
  
  The use of delayed-release doxylamine succinate and pyridoxine hydrochloride tablets show improved NVP symptom control as compared to placebo on Days 3,4 and 5, with sustained efficacy until the end of the trial.
  
  
  
  A four day study drug dosing trial with Diclegis® is sufficient to document efficacy, as the results are similar to those achieved after 14 study drug dosing days. The benefit seen at the earlier time validates drug efficacy and minimizes the natural course of improvement.
  
  
  
  CTR No. NCT006 14445 2007.
authors.affiliation: University of Toronto, Toronto, Canada. gidiup_2000@yahoo.com.|University of Western Ontario, London Ontario, Canada. gidiup_2000@yahoo.com.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA. gidiup_2000@yahoo.com.
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas, Medical Branch Galveston, Galveston, TX, USA.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Clark
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas, Medical Branch Galveston, Galveston, TX, USA.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA.
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Department of Obstetrics and Gynecology, University of Pittsburgh, Medical Center, Pittsburgh, PA, USA.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.affiliation: Medstar Health Research Institute, Hyattsville, MD, USA.|The Georgetown- Howard Universities Center for Clinical and Translational Science, Washington DC, USA.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.affiliation: Medstar Health Research Institute, Hyattsville, MD, USA.|The Georgetown- Howard Universities Center for Clinical and Translational Science, Washington DC, USA.|The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA.
authors.forename: Menachem
authors.initials: M
authors.lastname: Miodovnik
authors.affiliation: The Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver, National Institute of Child and Human Development, Bethesda, MD, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Mattison
authors.affiliation: University of Toronto, Toronto, Canada.|University of Western Ontario, London Ontario, Canada.|Division of Clinical Pharmacy, Institute of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Matok
mesh_terms: D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004025:Dicyclomine / Q000008:administration & dosage / Q000627:therapeutic use*; D004319:Doxylamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D048968:Morning Sickness / Q000188:drug therapy*; D011247:Pregnancy; D011736:Pyridoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000932:Antiemetics; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C004454:dicyclomine, doxylamine, pyridoxine drug combination; D004025:Dicyclomine; D004319:Doxylamine; D011736:Pyridoxine