Bonjesta for Morning Sickness

Recruiting at 9 trial locations

Overseen By Yvette Poindexter

Age: < 18

Sex: Female

Trial Phase: Phase 3

Sponsor: Duchesnay Inc.

Must not be taking: MAO inhibitors, Anticholinergics

Disqualifiers: Multifetal gestation, Epilepsy, Alcoholism, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 14 days

274 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of Bonjesta (a combination of doxylamine and pyridoxine) in treating morning sickness in pregnant teens compared to a placebo (a "dummy" treatment with no active ingredients). Researchers seek to determine whether Bonjesta can reduce nausea and vomiting during pregnancy and assess its safety for this age group. This trial may suit pregnant teens aged 12 to 17 years who experience morning sickness unrelieved by basic lifestyle changes. Eligible participants should be carrying a single baby, be between 7 and 15 weeks pregnant, and not have responded to usual dietary advice. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as antihistamines, anticholinergics, and drugs with anticholinergic activity, at least 48 hours before starting the study. You must also avoid taking any additional vitamin B6 supplements beyond your current multivitamin.

Is there any evidence suggesting that Bonjesta is likely to be safe for humans?

Research has shown that Bonjesta is generally safe for pregnant people. The FDA has approved it to treat nausea and vomiting during pregnancy. The most common side effect is drowsiness. Studies on a similar drug, Diclegis, found no risk of birth defects, suggesting that Bonjesta is well-tolerated. However, like any medicine, monitoring for unusual reactions is important. Always consult a doctor before starting any new treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for morning sickness?

Unlike standard treatments for morning sickness that often rely on medications like vitamin B6 and doxylamine separately, Bonjesta combines both ingredients in a single tablet. This combination approach is designed to enhance convenience and potentially improve adherence to the treatment regimen. Researchers are excited about Bonjesta because it simplifies the treatment process, offering a more streamlined option that could lead to better symptom management for expecting mothers.

What evidence suggests that Bonjesta might be an effective treatment for morning sickness?

Research has shown that Bonjesta, a combination of doxylamine and pyridoxine, effectively treats nausea and vomiting during pregnancy (NVP). Studies have found that using these two ingredients together can greatly reduce these symptoms without requiring higher doses. Participants in this trial may receive Bonjesta, which provides quick relief and continues to work throughout the day to manage morning sickness. Previous research indicates that treatments with these ingredients outperform a placebo, which is another arm in this trial. This combination is well-researched and has successfully managed NVP in many cases. ^{1 3 6 7 8}

Who Is on the Research Team?

Rafik Marouf, MD, PhD

Principal Investigator

Duchesnay Inc.

Are You a Good Fit for This Trial?

This trial is for pregnant adolescents in the US, aged 12-17 with a viable singleton pregnancy at 7-15 weeks gestation and experiencing morning sickness not improved by diet/lifestyle changes. They must be able to swallow pills whole, agree to follow study procedures, and not plan on ending their pregnancy. Those with certain health conditions or taking conflicting medications cannot participate.

Inclusion Criteria

The participant does not plan termination of the pregnancy

I tried changing my diet and lifestyle as advised but it didn't help.

I agree to keep taking my current multivitamin dose during the trial.

Exclusion Criteria

The participant has a condition for which antihistamines are contraindicated

I am taking or plan to take vitamin B6 supplements during the study.

The participant has a known hypersensitivity to specific medications

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive Bonjesta or placebo for the treatment of nausea and vomiting of pregnancy

14 days

3 visits (in-person), daily phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bonjesta
• Placebo

Trial Overview The trial tests Bonjesta's effectiveness against placebo in treating nausea and vomiting of pregnancy (NVP) among pregnant teenagers. Participants will receive either Bonjesta or a placebo pill to compare how well each works in managing NVP symptoms.

How Is the Trial Designed?

Group I: Bonjesta Active Control 1 Intervention

On Day 1, one tablet will be taken orally at bedtime. If this dose adequately controls symptoms (i.e., PUQE = 3), the participant will be directed to continue taking one tablet daily at bedtime only. However, on Day 2, if symptoms of nausea, retching and/or vomiting persist (i.e., PUQE score \>3), the participant will be directed to take her usual dose of 1 tablet at bedtime and an additional tablet the next morning on Day 3. The minimum dosage prescribed will be 1 tablet daily at bedtime, increasing, when indicated, to the maximal dosage of 2 tablets per day (one tablet in the morning and one tablet at bedtime) starting Day 3 and will continue through Day 14.

Group II: Placebo Placebo Group 1 Intervention

On Day 1, one tablet will be taken orally at bedtime. If this dose adequately controls symptoms (i.e., PUQE = 3), the participant will be directed to continue taking one tablet daily at bedtime only. However, on Day 2, if symptoms of nausea, retching and/or vomiting persist (i.e., PUQE score \>3), the participant will be directed to take her usual dose of 1 tablet at bedtime and an additional tablet the next morning on Day 3. The minimum dosage prescribed will be 1 tablet daily at bedtime, increasing, when indicated, to the maximal dosage of 2 tablets per day (one tablet in the morning and one tablet at bedtime) starting Day 3 and will continue through Day 14.

Bonjesta is already approved in United States for the following indications:

Approved in United States as Bonjesta for:

• Nausea and vomiting of pregnancy

Who Is Running the Clinical Trial?

Duchesnay Inc.

Lead Sponsor

Trials

7

Recruited

2,600+

Health Decisions

Collaborator

Trials

31

Recruited

14,000+

Premier Research

Collaborator

Published Research Related to This Trial

In a case of severe diphenhydramine-induced antimuscarinic delirium, the combination of physostigmine and transdermal rivastigmine was effective in resolving symptoms without any observed adverse effects, suggesting rivastigmine as a potential alternative during physostigmine shortages.

The patient experienced persistent antimuscarinic symptoms like dry mouth and difficulty urinating after rivastigmine was discontinued, but did not develop muscarinic toxicity, indicating that rivastigmine can be safely used in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diphenhydramine-Induced Antimuscarinic Delirium Treated with Physostigmine and Transdermal Rivastigmine. Whitledge, JD., Watson, CJ., Simpson, M., et al.[2023]

Doxylamine succinate and pyridoxine hydrochloride, combined as Diclegis, is the only FDA-approved medication for treating nausea and vomiting in pregnancy (NVP), addressing a significant treatment gap since the removal of Bendectin over 30 years ago.

Diclegis has a strong safety profile, qualifying for FDA Pregnancy Category A status, making it a recommended first-tier treatment option for managing NVP due to its proven efficacy and safety in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxylamine succinate-pyridoxine hydrochloride (Diclegis) for the management of nausea and vomiting in pregnancy: an overview. Nuangchamnong, N., Niebyl, J.[2021]

For patients with moderate-to-severe morning sickness who do not fully respond to doxylamine and pyridoxine, it is important to consider adding another medication based on a structured algorithm.

The Motherisk algorithm prioritizes treatments that are both effective and safe for the fetus, ensuring that the management of morning sickness is evidence-based.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nausea and vomiting of pregnancy. Evidence-based treatment algorithm. Levichek, Z., Atanackovic, G., Oepkes, D., et al.[2018]

In a study involving 42 patients with dyspepsia, hiatus hernia, or duodenal ulcer, dicyclomine (Merbentyl) effectively controlled symptoms without the need for additional antacids or placebo treatments.

The study was conducted under double-blind conditions, showing that while patients preferred taking frequent treatments, dicyclomine alone was sufficient for symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of dicyclomine with antacid and without antacid in dyspepsia. Kagan, G., Huddlestone, L., Wolstencroft, P.[2017]

The combination of doxylamine succinate and pyridoxine hydrochloride (Diclegis®) significantly improves symptoms of nausea and vomiting in pregnancy (NVP) compared to placebo, with efficacy observed as early as Days 3, 4, and 5 of treatment.

A shorter treatment duration of just four days is sufficient to demonstrate the drug's effectiveness, which aligns with the results seen after the full 14-day treatment period, suggesting that early intervention can effectively manage NVP symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demonstration of early efficacy results of the delayed-release combination of doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy. Koren, G., Clark, S., Hankins, GD., et al.[2018]

Diclegis®, a combination of doxylamine and pyridoxine, was approved by the FDA in April 2013 as a safe treatment for morning sickness during pregnancy, classified as a pregnancy category A drug, indicating strong evidence of fetal safety.

This approval marks a significant advancement after 30 years without an FDA-approved treatment for morning sickness, providing a therapeutic option that could benefit millions of pregnant women and their healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The return to the USA of doxylamine-pyridoxine delayed release combination (Diclegis®) for morning sickness--a new morning for American women. Koren, G.[2020]

A new chewable tablet formulation combining meclizine and pyridoxine has been developed to provide rapid absorption and improve patient acceptance, especially for those experiencing nausea and vomiting.

The formulation demonstrated excellent dissolution profiles and was well-received in taste tests, indicating its potential as an effective and palatable treatment option for motion sickness across all age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation of New Chewable Oral Dosage Forms of Meclizine and Pyridoxine Hydrochloride. Al-Madhagi, WM., Alshargabi, A., Alzomor, AKY., et al.[2023]

In a study of 28 patients with suspected gastrointestinal motility disorders, neostigmine significantly increased motor activity in the stomach and small intestine, indicating its potential efficacy in treating conditions like gastroparesis and intestinal dysmotility.

The increase in motor activity was observed in a majority of patients with reduced contractile responses after meals, but interestingly, the effects were not more pronounced in patients with cardiovagal dysfunction, suggesting that the mechanism of action may not be influenced by this specific type of nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders. Parthasarathy, G., Ravi, K., Camilleri, M., et al.[2018]

In a 4-week study involving 100 patients with non-ulcer dyspepsia and erosive prepyloric changes, treatment with Al-Mg antacids and pirenzepine did not show significant superiority over placebo in improving symptoms or changing the grade of erosive prepyloric changes.

While no serious side effects were reported, xerostomia (dry mouth) was more common in patients taking pirenzepine compared to those on placebo, indicating a potential side effect of this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose antacids and pirenzepine in the treatment of patients with non-ulcer dyspepsia and erosive prepyloric changes. A randomized, double-blind, placebo-controlled trial. Weberg, R., Berstad, A.[2019]

Pralidoxime was successfully used to treat a pediatric patient who ingested rivastigmine, showing clinical improvement in symptoms of cholinergic syndrome after administration.

This case suggests that pralidoxime can be an effective treatment for acetylcholinesterase inhibitor poisoning, as indicated by the patient's increased plasma cholinesterase levels following treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The First Use of Pralidoxime in a Child With Rivastigmine Poisoning. Saz, EU., Yurtseven, A., Kilinç, MA., et al.[2018]

The herbal medicinal product STW 5 has been shown to be an effective alternative to metoclopramide and cisapride for treating functional gastrointestinal disorders, supported by randomized controlled trials.

STW 5 has a favorable safety profile, allowing for long-term use in patients without the restrictions that apply to other prokinetic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders. Madisch, A., Vinson, BR., Abdel-Aziz, H., et al.[2018]

In a study involving 20 participants with motion sickness, the transdermal system Scopoderm TTS (scopolamine) was found to be as effective as the oral antiemetic dimenhydrinate during a 1-hour test flight.

Scopoderm TTS offers a significant advantage for long-distance travel, providing effective motion sickness prevention for up to 72 hours, compared to the shorter duration of dimenhydrinate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparative in-flight study of a scopolamine-containing membrane plaster versus dimenhydrinate under defined acceleration conditions]. Offenloch, K., Zahner, G., Dietlein, G., et al.[2018]

In a randomized trial involving 256 pregnant women, Diclectin significantly improved symptoms of nausea and vomiting of pregnancy compared to placebo, with a notable difference in the pregnancy unique quantification of emesis score.

The majority of women taking Diclectin expressed a desire to continue using the medication after the trial, indicating its effectiveness and tolerability in managing their symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Koren, G., Clark, S., Hankins, GD., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3990370/

Doxylamine succinate–pyridoxine hydrochloride (Diclegis) for ... Doxylamine and pyridoxine have become the most studied drugs for NVP, and their use may alleviate many women's symptoms without the need for escalation.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10853031/

Nausea and Vomiting of Pregnancy and its Management ... Additionally, pyridoxine (vitamin B 6 ) has been shown to be effective in treating NVP, supported by several trials 48 50 51 . Also, although ...

3. hcp.bonjesta.com hcp.bonjesta.com/safety-and-efficacy

Safety And Efficacy | Bonjesta - Healthcare Professional Bonjesta offers rapid relief of NVP symptoms and a sustained therapeutic effect, controlling nausea and vomiting symptoms that occur in the morning, during the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05289557

The Efficacy and Safety of Bonjesta® for Nausea ... The primary objective of this study is to compare the efficacy of Bonjesta for the treatment of nausea and vomiting of pregnancy (NVP) in pregnant ...

5. ajog.org ajog.org/article/S0002-9378(10)00914-2/abstract

Effectiveness of delayed-release doxylamine and ... Diclectin use resulted in a significantly larger improvement in symptoms of nausea and vomiting of pregnancy compared with placebo based on both the pregnancy ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/doxylamine-and-pyridoxine-oral-route/description/drg-20060896

Doxylamine and pyridoxine (oral route) - Side effects & ... Doxylamine and pyridoxine combination is used to treat nausea and vomiting in pregnant women (also called morning sickness) ... Safety and ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/021876s002lbl.pdf

Diclegis (doxylamine succinate and pyridoxine hydrochloride ... The safety and efficacy of DICLEGIS were compared to placebo in a double-blind, randomized, multi-center trial in 261 women with nausea and vomiting of ...

8. canada.ca canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-assessing-diclectin-doxylamine-pyridoxine-combination-safety-pregnancy.html

DICLECTIN (doxylamine and pyridoxine combination) The safety information reviewed on Diclectin and birth defects (fetal adverse events) showed no change in the safety profile of Diclectin in pregnant women. The ...