This is a secondary analysis of a double-blind, randomized, multicenter, placebo-controlled study of the delayed-release combination of doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) (Diclegis®) in the treatment of NVP [12]. The study was approved by the IRB of the University of Texas, Galveston, University of Pittsburg and Georgetown University. The subjects were pregnant, at least 18 years of age, in the gestational age range of 7–14 weeks, suffering from NVP, had a PUQE score ≥ 6) [13-15], and had not responded to conservative management consisting of dietary/lifestyle advice [16]. Women treated by other antiemetics, suffering from chronic medical conditions, or those who could not communicate in either English or Spanish, were excluded. After physical examination and laboratory tests (hemoglobin and blood count, liver function tests, electrolytes, amylase), and after confirming in utero singleton pregnancies by ultrasound, women were randomized, using a computerized program, to receive Diclegis® (doxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg) or placebo of similar look. Two tablets of study drug (Diclegis® or placebo) were administered at bedtime on Day 1. If symptoms of nausea and vomiting persisted into the afternoon hours of Day 2 (i.e., PUQE Score above 3), the subject was directed to take her usual dose of 2 tablets at bedtime and an additional tablet the next morning on Day 3. Based upon assessment in the clinic on Day 4 (+/−1 day), the subject might have been directed to take an additional 4th tablet mid-afternoon to control evening symptoms. The minimum assigned study medication was 2 tablets daily at bedtime, increasing when indicated to the maximal dosage of 4 tablets per day according to the timing, duration, severity, and frequency of the symptoms experienced by the subject. The study had a 15 day period consisting of 14 dosing days. Telephone contact was made on day 2, 6, 12, and 14 in order to assess subject diary information, adverse events (AEs), concomitant medications, and compliance with the study medication. Patients returned to the clinic in the morning prior to their morning dose on Day 4 (+/− 1 day), Day 8 (+/− 1 day), and on Day 15 (+/− 1 day; end of study visit) to collect diary report and complete all study related data.
Subjects completed the Pregnancy-Unique Quantification of Emesis (PUQE) score and the study diary (once daily every morning prior to study dose at approximately the same time each day). They also completed the Global Assessment of Well Being scale of the PUQE on Days 1, 8, and 14 at the same time the PUQE score was completed.
Adverse events and concomitant medications were recorded at all visits and follow-up phone calls. An additional follow-up phone call was conducted 30 days after last dosing to capture serious adverse events for patients completing the treatment period or early termination.
The results of the effectiveness of the drug in this trial have been previously published [12].
The frequency and severity of all AEs were tabulated by treatment group, system organ class, preferred term severity, and relationship to study drug. In addition, laboratory tests were conducted on Days 1 and15 (±1 day).
Adverse events (AEs) experienced by the subjects that occurred on or after Day 1 (after the patient signed the informed consent form) through Day 15, were compared between groups using Pearson’s Chi-square test or Fisher’s exact test if more appropriate. The available sample size has 80% power to show a doubling in CNS depression with alpha of 5%.
