Xonvea clinical trials data

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Xonvea is designed specifically for the treatment of NVP and studies indicate no fetal toxicity of Xonvea in pregnant women1

  • Over 33,000,000 pregnant women between 1956-19832,10
  • 40 years of data in pregnant women2,3
  • 2 meta-analyses involving data from more than 200,000 pregnancies4,5

Clinical study design6

A phase III randomised, double-blind, multicentre, placebo-controlled trial, recruited pregnant adult women (n=298) with NVP (mean gestational age 9.3 weeks at enrolment) who had previously failed to respond to conservative management.

Participants were randomised in a 1:1 ratio to receive delayed-release 10mg doxylamine/10mg pyridoxine combination, or placebo for 14 days.

Primary Endpoint

The primary endpoint included the change from baseline in the two elements of the PUQE score.

  • Symptoms element of the PUQE score is the number of daily vomiting episodes, number of daily retching, and length of daily nausea in hours, for an overall score of symptoms rated from 3 (no symptoms) to 15 (most severe).
  • Quality of life element of the PUQE score is the patients’ report on their well-being from zero (worst possible) to 10 (best possible and is a set of five patient self-score questions which are answered daily.

 

Secondary Endpoint

Secondary effectiveness criteria included:

  • Day-by-day area under the curve for change in PUQE from baseline.
  • Time loss from employment.
  • The number of women in each arm who continued with (blinded) compassionate use of her medication.
  • The number of patients who reported concurrent use of alternate therapy for NVP was also recorded and included management strategies such as nutritional modifications, teas, aroma therapy, massage, and yoga.

NVP symptoms and impact on quality of life were evaluated daily using both domains of the validated Pregnancy-Unique Quantification of Emesis scale (PUQE) and the mean difference in score from baseline to day 15 constituted the primary endpoint.

To view the PUQE score, please click here.

Results of study6,7

Xonvea significantly improved the symptoms of NVP and the quality of life versus placebo.

Primary endpoints:

A consistently significant reduction in NVP symptoms as per PUQE symptom score.

The Quality of Life domain of the PUQE score showed a statistically-significant difference in the Global Assessment of Well-being (GAWB) scores from baseline to day 15: those women taking doxylamine 10mg/pyridoxine 10mg scored significantly better versus placebo (2.8 vs. 1.8; P=0.005 at 95% CI). This is a proven, validated and recognised assessment tool for measuring QOL in patients with NVP.8,9

Secondary endpoints:


After the trial, 64 (48.9%) significantly more women receiving doxylamine/pyridoxine combination asked to continue compassionate use of their medication, as compared with 41 (32.8%) of placebo-treated women (P=0.009). Likewise, significantly more women receiving placebo (n=46, 36%) than doxylamine/pyridoxine (n=31, 23.7%) required additional alternative therapies to manage their NVP symptoms (P=0.04).

A secondary measure of efficacy was the observed loss of time from employment, which was numerically greater in the placebo group (2.37 days ± 10.23) than in the doxylamine/pyridoxine group (0.92 days ± 3.86). Not statistically significant (P=0.06).

Xonvea – side effect profile1

Xonvea contains the most studied drug combination in pregnancy, designed specifically for NVP, with over 33,000,000 prescriptions between 1956-1983,2,10 40 years of data in pregnant women and 2 meta-analyses involving data from more than 200,000 pregnancies.2-5

There has been vast clinical experience regarding the use of the Xonvea combination (doxylamine/pyridoxine combination) use in pregnancy dating back to 1956.1,2

Adverse events include:1

  • Nervous system disorders: somnolence (very common); dizziness (common)
  • Gastrointestinal disorders: dry mouth (common)
  • General disorders and administration site conditions: fatigue (common).

Please read the product’s prescribing information for a full list of the adverse events for this medication and refer to the Summary of Product characteristics before prescribing. Click here for prescribing information and adverse events reporting.

You can also visit our safety and historical use page for more information.

References:

  1. Xonvea 10 mg/10 mg gastro-resistant tablets Summary of Product Characteristics.
  2. Madjunkova S, Maltepe C, Koren G. The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin®) for the treatment of nausea and vomiting of pregnancy. Pediatr Drugs 2014; 16: 199-211.
  3. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 189, January 2018. Nausea and vomiting of pregnancy. Obstet. Gynecol. 2018;131:e15-e30.
  4. Einarson T, Leeder J, Koren G. A method for meta-analysis of epidemiological studies. Drug Intell Clin Pharma 1988; 22(10):813-824.
  5. McKeigue P, Lamm S, Linn S, Kutcher J. Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies. Teratology 1994; 50(1): 27-37.
  6. Koren G, Clark S, Hankins GDV, Caritis SN, et al. Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. American Journal of Obstetrics & Gynaecology. 2010;203:571.e1–571.e7.
  7. Koren G et al. Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy. BMC Pregnancy and Childbirth (2016) 16:371.
  8. Koren G, Piwko C, Ahn E, et al. Validation studies of the Pregnancy Unique-Quantification of Emesis (PUQE) scores. J Obstet Gynaecol. 2005;25(3):241-244.
  9. Royal College of Obstetricians and Gynaecologists. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum (Green-top Guideline No. 69). 22 June 2016. Royal College of Obstetricians and Gynaecologists: London. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg69/.
  10. Ornstein, M., Einarson, A., Koren, G. Bendectin/Diclectin for morning sickness: A Canadian follow-upof an American tragedy. Reproductive Toxicology. 1995; 9(1): 1-6.