Clinical trial NCT00614445: The Efficacy Of Diclectin® For Nausea And Vomiting Of Pregnancy
Official title: A Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial Of The Efficacy Of Diclectin® For Nausea And Vomiting Of Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Nausea and Vomiting of Pregnancy
Keywords: Nausea
Vomiting
Pregnancy
Hyperemesis gravidarum
Pregnancy complications
Lead sponsor: Duchesnay Inc.
Sponsor class: INDUSTRY
Collaborators: name: Premier Research Group plc
First posted: 2008-02-13
Enrollment: 280
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Diclectin® (doxylamine succinate USP 10 mg and pyridoxine HCl 10 mg) is more effective at controlling the nausea and vomiting of pregnancy than a placebo.

Detailed description: Nausea and vomiting of pregnancy (NVP), also known as "morning sickness," is a common condition that affects a large percentage of pregnant women. The symptoms can range from mild nausea to severe nausea and vomiting for which a woman may need to be hospitalized. Nausea and vomiting of pregnancy can affect a woman's quality of life and ability to conduct daily activities.

Diclectin® is a combination of 10 mg doxylamine succinate (an antihistamine), and 10 mg pyridoxine hydrochloride (vitamin B6) in a delayed release tablet formulation. It has been commercially available in Canada for the management of NVP for over 25 years and has been prescribed to over 33 million pregnant women.

Presently, there is no Food Drug and Administration (FDA) approved drug on the market to treat the symptoms of NVP. This study will test the efficacy of Diclectin® (doxylamine 10 mg, pyridoxine 10 mg in a delayed-release formulation) for NVP.

Patients enrolled in the study will receive between 2 and 4 tablets of Diclectin® or placebo daily, depending on their symptoms for up to 14 days. Patients will assess their symptoms of nausea and vomiting daily using a standardized questionnaire.

Eligibility criteria: Inclusion Criteria:

* The patient has signed a written informed consent to participate in the study and has agreed to follow dosing instructions and complete all required study visits.
* The patient is a pregnant female age equal to or greater than 18 years old.
* The patient's entry ultrasound indicates a viable pregnancy and confirms gestational age of the fetus is 7-14 weeks at the anticipated time of the first dose of study medication or placebo. If an ultrasound was done within 4 weeks of the admission visit, and results can be obtained, an additional ultrasound is not necessary.
* The patient is suffering from NVP and has a Pregnancy Unique Quantification of Emesis (PUQE) score ≥6.
* The patient has not responded to conservative management consisting of dietary/lifestyle advice according to the 2004 ACOG Practice Bulletin.
* The patient agrees, if on a multivitamin, to continue on their current dose of multivitamin for the duration of the trial.
* The patient does not plan termination of the pregnancy.

Exclusion Criteria:

* The investigator confirms the patient's nausea and vomiting is of etiology other than Nausea and Vomiting of Pregnancy (NVP).
* The patient has gestational trophoblastic disease or multifetal gestation.
* The patient has a condition for which antihistamines, in the opinion of the investigator, are contraindicated (epilepsy, alcoholism, glaucoma, chronic lung disease, urinary retention, heart block, etc.).
* The patient has used antihistamines, anticholinergics, dopamine antagonists, serotonin antagonists, ginger, or anti-emetic therapy (including acupressure, acupuncture, homeopathic remedies, medical hypnosis, relief bands etc) to treat NVP in the previous 48 hours or plans to do so during the study .
* The patient is using drugs that have anticholinergic activity (e.g., tricyclic antidepressants).
* The patient is taking multivitamins containing more than 10 mg of vitamin B6, or plans to do so during the study.
* The patient is taking supplementary vitamin B6 in addition to any multivitamin preparation, or plans to do so during the study.
* The patient is currently drinking any amount of alcohol.
* The patient has any condition that might interfere with the conduct of the study.
* The patient is likely to be unable to comply with study procedures because of inadequate cognitive skills.
* The patient has received an investigational drug within 30 days before enrollment in this study or is scheduled to receive an investigational drug during the course of this study.

Primary outcomes:
measure: Diclectin Versus Placebo for Treatment of Nausea and Vomiting of Pregnancy (NVP) as Measured by the Change in Pregnancy Unique-Quantification of Emesis (PUQE) Overall Score of Symptoms From Baseline (Day 1) to End of Study Visit (Day 15).
timeFrame: Baseline (Day 1) to End of Study Visit Day 15 (± 1 day)
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Washington Hospital Center Physicians
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Bethesda
country: United States
facility: National Naval Medical Center
state: Maryland
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of University of Pittsburgh Medical Center
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Pasadena
country: United States
facility: UTMB Pasadena Clinic
state: Texas
city: Pearland
country: United States
facility: UTMB Regional Maternal & Child Health Program--Pearland Clinic
state: Texas
Study officials:
affiliation: Duchesnay Inc.
name: Liubov Gargaun, M.D.
role: STUDY_DIRECTOR
affiliation: Motherisk Program, University of Toronto
name: Gideon Koren, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Gary Hankins, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Persaud N, Meaney C, El-Emam K, Moineddin R, Thorpe K. Doxylamine-pyridoxine for nausea and vomiting of pregnancy randomized placebo controlled trial: Prespecified analyses and reanalysis. PLoS One. 2018 Jan 17;13(1):e0189978. doi: 10.1371/journal.pone.0189978. eCollection 2018.
citation: Koren G, Clark S, Hankins GD, Caritis SN, Umans JG, Miodovnik M, Mattison DR, Matok I. Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy. BMC Pregnancy Childbirth. 2016 Nov 24;16(1):371. doi: 10.1186/s12884-016-1172-9.
citation: Koren G, Hankins GD, Clark S, Caritis SN, Miodovnik M, Umans JG, Mattison DR. Effectiveness of doxylamine-pyridoxine for morning sickness. Am J Obstet Gynecol. 2016 May;214(5):664-6. doi: 10.1016/j.ajog.2016.01.186. Epub 2016 Feb 1. No abstract available.
citation: Koren G, Clark S, Hankins GD, Caritis SN, Umans JG, Miodovnik M, Mattison DR, Matok I. Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial. BMC Pregnancy Childbirth. 2015 Mar 18;15:59. doi: 10.1186/s12884-015-0488-1.
citation: Matok I, Clark S, Caritis S, Miodovnik M, Umans JG, Hankins G, Mattison DR, Koren G. Studying the antiemetic effect of vitamin B6 for morning sickness: pyridoxine and pyridoxal are prodrugs. J Clin Pharmacol. 2014 Dec;54(12):1429-33. doi: 10.1002/jcph.369. Epub 2014 Aug 7.
citation: Costantine MM, Matok I, Chiossi G, Clark S, Miodovnik M, Umans JG, Caritis S, Hankins GD, Koren G. Determinants of adherence to delayed-release doxylamine and pyridoxine in patients with nausea and vomiting of pregnancy. Ther Drug Monit. 2012 Oct;34(5):569-73. doi: 10.1097/FTD.0b013e31826e7997.
citation: Koren G, Clark S, Hankins GD, Caritis SN, Miodovnik M, Umans JG, Mattison DR. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010 Dec;203(6):571.e1-7. doi: 10.1016/j.ajog.2010.07.030. Epub 2010 Sep 16.