Nausea and Vomiting of Pregnancy
Conditions
Keywords
Nausea, Vomiting, Pregnancy, Hyperemesis gravidarum, Pregnancy complications
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.
Interventions
DRUGdoxylamine succinate 10 mg/pyridoxine hydrochloride 10 mg
up to 4 tablets daily, titrated according to the protocol
DRUGPlacebo
2 to 4 tablets daily titrated according to the protocol
Sponsors
Premier Research
Duchesnay Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| Diclectin® Diclectin® (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) delayed release tablet | 140 |
| Placebo Placebo tablets identical in size, shape, taste, and color to the experimental treatment (Diclectin®) | 140 |
| Total | 280 |
Baseline characteristics
| Characteristic | Placebo | Diclectin® | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 140 Participants | 140 Participants | 280 Participants |
| Age, Continuous | 25.0 years STANDARD_DEVIATION 5.6 | 25.9 years STANDARD_DEVIATION 6 | 25.5 years STANDARD_DEVIATION 5.8 |
| Region of Enrollment United States | 140 participants | 140 participants | 280 participants |
| Sex: Female, Male Female | 140 Participants | 140 Participants | 280 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 65 / 133 | 63 / 128 |
| serious Total, serious adverse events | 4 / 133 | 5 / 128 |
Outcome results
Primary
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).
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)
Population: 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 | Measure | Value (MEAN) |
|---|---|---|
| Diclectin® | 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). | -4.8 PUQE Score |
| Placebo | 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). | -3.9 PUQE Score |