The Efficacy Of Diclectin® For Nausea And Vomiting Of Pregnancy

• Sponsor: Duchesnay Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00614445
• Collaborator: Premier Research Group plc (Industry)
• Enrollment: 280
• Locations: 7
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 40
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Nausea and Vomiting of Pregnancy	Drug: doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial Of The Efficacy Of Diclectin® For Nausea And Vomiting Of Pregnancy
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diclectin® Diclectin® (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) delayed release tablet	Drug: doxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg; up to 4 tablets daily, titrated according to the protocol; Other Names: Diclectin®
Placebo Comparator: Placebo Placebo tablets identical in size, shape, taste, and color to the experimental treatment (Diclectin®)	Drug: Placebo; 2 to 4 tablets daily titrated according to the protocol

Outcome Measures

Primary Outcome Measures

1. 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). [Baseline (Day 1) to End of Study Visit Day 15 (± 1 day)]

   The objective of this double-blind, randomized, placebo-controlled study was to assess the efficacy, safety, and tolerability of oral Diclectin® in the treatment of nausea and vomiting of pregnancy (NVP) as measured by the Pregnancy Unique-Quantification of Emesis (PUQE) overall score of symptoms from baseline (Day 1) to end of study visit (Day 15). The PUQE score measured hours of nausea, number of times vomiting, and number of times retching for a TOTAL overall score of symptoms on a scale rated from 3 (no symptoms) to 15 (most severe).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington Hospital Center Physicians	Washington	District of Columbia	United States	20010
2	Georgetown University Hospital	Washington	District of Columbia	United States	20057
3	National Naval Medical Center	Bethesda	Maryland	United States	20889
4	Magee-Womens Hospital of University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
5	University of Texas Medical Branch	Galveston	Texas	United States	77555-0587
6	UTMB Pasadena Clinic	Pasadena	Texas	United States	77502
7	UTMB Regional Maternal & Child Health Program--Pearland Clinic	Pearland	Texas	United States	77581

Sponsors and Collaborators

• Duchesnay Inc.
• Premier Research Group plc

Investigators

• Study Director: Liubov Gargaun, M.D., Duchesnay Inc.
• Principal Investigator: Gideon Koren, M.D., Motherisk Program, University of Toronto
• Principal Investigator: Gary Hankins, M.D., University of Texas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duchesnay Inc.
• ClinicalTrials.gov Identifier: NCT00614445
• Other Study ID Numbers: DIC-301
• First Posted: Feb 13, 2008
• Last Update Posted: Nov 23, 2021
• Last Verified: Aug 1, 2011

• Keywords provided by Duchesnay Inc.: Nausea; Vomiting; Pregnancy; Hyperemesis gravidarum; Pregnancy complications
• Additional relevant MeSH terms: Pregnancy Complications; Nausea; Vomiting; Pyridoxine; Vitamin B 6; Doxylamine; Doxylamine succinate

Study Results

Participant Flow

Recruitment Details	This is a double-blind, randomized, multicenter, placebo-controlled study in the treatment of NVP. On Day 1, all patients will receive 2 tablets of study drug at bedtime. During Days 2-14 the patients will receive 2 tablets of study drug at bedtime plus additional study drug based upon the need for control of their nausea and vomiting.
Pre-assignment Detail	The minimum dosage will be 2 tablets daily at bedtime, increasing, when indicated, to the maximal dosage of 4 tablets per day. After randomization, patients will return to the clinic for evaluation on Day 4 (+/-1 day) and Day 8 (+/-1 day), and will return on Day 15 (+/-1 day) for an end of study visit. The study duration is expected to be 15 days.

Arm/Group Title	Diclectin®	Placebo
Arm/Group Description	Diclectin® (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) delayed release tablet	Placebo tablets identical in size, shape, taste, and color to the experimental treatment (Diclectin®)
Period Title: Overall Study
STARTED	140	140
COMPLETED	112	91
NOT COMPLETED	28	49

Baseline Characteristics

Arm/Group Title	Diclectin®	Placebo	Total
Arm/Group Description	Diclectin® (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) delayed release tablet	Placebo tablets identical in size, shape, taste, and color to the experimental treatment (Diclectin®)	Total of all reporting groups
Overall Participants	140	140	280
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	140 100%	140 100%	280 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.9 (6.0)	25.0 (5.6)	25.5 (5.8)
Sex: Female, Male (Count of Participants)
Female	140 100%	140 100%	280 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	140 100%	140 100%	280 100%

Outcome Measures

1. Primary Outcome

Title	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).
Description	The objective of this double-blind, randomized, placebo-controlled study was to assess the efficacy, safety, and tolerability of oral Diclectin® in the treatment of nausea and vomiting of pregnancy (NVP) as measured by the Pregnancy Unique-Quantification of Emesis (PUQE) overall score of symptoms from baseline (Day 1) to end of study visit (Day 15). The PUQE score measured hours of nausea, number of times vomiting, and number of times retching for a TOTAL overall score of symptoms on a scale rated from 3 (no symptoms) to 15 (most severe).
Time Frame	Baseline (Day 1) to End of Study Visit Day 15 (± 1 day)

Outcome Measure Data

Analysis Population Description

Planned: Approximately 280 subjects (140 subjects per treatment group) were to be enrolled to achieve 200 evaluable subjects. Analyzed: 280 enrolled subjects [261 subjects in the intent-to-treat safety (ITT-S) population; 256 subjects in the intent-to-treat efficacy (ITT-E) population].

Arm/Group Title	Diclectin®	Placebo
Arm/Group Description	Diclectin® (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) delayed release tablet	Placebo tablets identical in size, shape, taste, and color to the experimental treatment (Diclectin®)
Measure Participants	140	140
Mean (95% Confidence Interval) [PUQE Score]	-4.8	-3.9

Adverse Events

Arm/Group Title	Diclectin®		Placebo
Arm/Group Description	Diclectin® (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) delayed release tablet		Placebo tablets identical in size, shape, taste, and color to the experimental treatment (Diclectin®)
All Cause Mortality
	Diclectin®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Diclectin®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/133 (3%)		5/128 (3.9%)
Hepatobiliary disorders
Bile duct stone	0/133 (0%)	0	1/128 (0.8%)	1
Pregnancy, puerperium and perinatal conditions
Intra-uterine Death	1/133 (0.8%)	1	0/128 (0%)	0
Abortion missed	1/133 (0.8%)	1	0/128 (0%)	0
Abortion spontaneous	1/133 (0.8%)	1	0/128 (0%)	0
Abortion spontaneous	0/133 (0%)	0	1/128 (0.8%)	1
Abortion missed	0/133 (0%)	0	1/128 (0.8%)	1
Premature rupture of membrane	0/133 (0%)	0	1/128 (0.8%)	1
Foetal disorder	0/133 (0%)	0	1/128 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Diclectin®		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/133 (48.9%)		63/128 (49.2%)
Gastrointestinal disorders
Adominal Pain	5/133 (3.8%)	5	8/128 (6.3%)	8
General disorders
Fatigue	9/133 (6.8%)	9	8/128 (6.3%)	8
Musculoskeletal and connective tissue disorders
Back pain	7/133 (5.3%)	7	4/128 (3.1%)	4
Nervous system disorders
Dizziness	8/133 (6%)	8	8/128 (6.3%)	8
Headache	17/133 (12.8%)	17	20/128 (15.6%)	20
Somnolence	19/133 (14.3%)	19	15/128 (11.7%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No unpublished data given to the investigator may be transmitted to a third party without prior approval of the sponsor in writing. No publications or communications involving the results of the trial are authorized without prior review and written consent from the sponsor. The investigator must agree to send the sponsor for review prior to their submission. The sponsor reserves the right to delete from such materials any part or parts deemed to be confidential or proprietary.