Evaluation of Doxylamine Hydrogen Succinate and Pyridoxine Hydrochloride in Pregnant Women with Nausea and Vomiting: A Multicenter, Open-Label Study

Trial ID: 2023-505144-19-00
Protocol: RES-6131-C1
Sponsor: Itf Research Pharma S.L.

Trial statistics

science

test molecule

location_city

research sites

public

country

medical_information

disease

person_search

investigators

handshake

vendor

Diseases & Conditions

Morning sickness

Objectives

The primary objective of this clinical trial is to evaluate the **efficacy** of treatment with the fixed combination of doxylamine/pyridoxine 10/10 mg modified-release hard capsules on the quality of life of pregnant women experiencing nausea and vomiting of pregnancy (NVP) after 14 days of administration. This is clinically relevant as NVP can significantly impact the well-being and daily functioning of pregnant women, and effective management is crucial for improving their quality of life.

Secondary objectives include:

Evaluating the efficacy of the treatment on the quality of life after 7 days and between 7 and 14 days of administration.
Assessing the daily efficacy of the treatment on nausea and vomiting throughout the study.
Describing the maximum guidelines achieved after 14 days, the patient profile associated with each regimen, and the time taken to reach the maximum regimen.
Evaluating the time of onset and duration of effect perceived by the patient after the first administration.
Assessing the safety of the treatment during the study period.
Evaluating therapeutic compliance by patient and by regimen used after 14 days.
Assessing patient satisfaction with the treatment after 14 days of administration.
Evaluating investigator satisfaction with the treatment after 14 days of administration.

Participants

The clinical trial focuses on evaluating the efficacy of a treatment for **nausea and vomiting of pregnancy**. The study population comprises pregnant adult women aged between 18 and 45 years, with a gestational age ranging from 5 to 12 weeks. Participants are required to have confirmed clinical pregnancy viability via ultrasound prior to inclusion. The trial exclusively involves female subjects, and the population is considered vulnerable due to the pregnancy status. Participants must present with nausea and vomiting of pregnancy with a PUQE intensity of 6 or higher. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific inclusion criteria, including the absence of prior treatment with Doxylamine/Pyridoxine exceeding a daily dose of 20/20 mg in the five days preceding the study. Participants are expected to adhere to the investigational product's administration instructions and complete all study visits. Lifestyle factors such as diet and physical activity are not specified in the available data.

Plans and Procedures

The clinical trial is a **prospective**, multicentre, open-label study designed to evaluate the efficacy of a fixed-dose combination of **doxylamine hydrogen succinate** and **pyridoxine hydrochloride** in modified-release capsules on the quality of life of pregnant women experiencing **nausea and vomiting of pregnancy** (NVP). The trial will involve adult pregnant women aged 18 to 45 years, with a gestational age between 5 and 12 weeks, who have not previously received the investigational product or have received it in limited doses. The study will be conducted over a period of 14 days, with the primary endpoint being the difference in the global score of the NVPQoL scale after treatment compared to baseline.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on gestational age, clinical pregnancy viability, and the intensity of NVP symptoms. Follow-up visits will occur at 7 and 14 days to assess changes in the NVPQoL score, the evolution of nausea and vomiting, and the safety profile through the incidence of adverse events. The end-of-study visit will coincide with the 14-day follow-up, where the primary and secondary endpoints will be evaluated, including patient and investigator satisfaction, therapeutic compliance, and the frequency of maximum treatment guidelines reached.

The expected length of participant involvement is 14 days, with conditions for early termination including withdrawal of consent, non-compliance with the study protocol, or the occurrence of serious adverse events. The trial is categorized as a Phase IV study, indicating it is a post-marketing surveillance trial to further assess the treatment's effectiveness and safety in a real-world setting. The investigational product will be administered orally, with a maximum daily dose of 40 mg and a total dose not exceeding 580 mg over the treatment period. The trial is anticipated to start recruitment in August 2023 and conclude by September 2024.

Treatment

The clinical trial involves the administration of **Cariban**, a fixed-dose combination medication containing **doxylamine hydrogen succinate** and **pyridoxine hydrochloride**. This experimental medication is provided in the form of modified-release hard capsules, with each capsule containing 10 mg of doxylamine hydrogen succinate and 10 mg of pyridoxine hydrochloride. The route of administration is oral. Participants are instructed to take the medication as per the dosing schedule, which allows for a maximum daily dose of 40 mg and a total maximum dose of 580 mg over the course of the treatment period. The treatment duration is set for a maximum of 14 days. Compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the efficacy of the Cariban capsules in improving the quality of life for pregnant women experiencing nausea and vomiting of pregnancy. The trial is designed to assess the impact of the medication over a 14-day period, with careful monitoring of participant compliance and response to the treatment.

Efficacy

The efficacy of the fixed-dose combination of **Doxylamine** and **Pyridoxine** 10/10 mg modified-release capsules will be assessed in a clinical trial involving pregnant women experiencing nausea and vomiting of pregnancy (NVP). The primary endpoint for evaluating efficacy is the difference in the global score of the NVP Quality of Life (NVPQoL) scale after 14 days of treatment compared to baseline. Secondary endpoints include the difference in NVPQoL scores after 7 days of treatment, the evolution of nausea and vomiting assessed daily using the PUQE-24 scale, and the frequency of subjects categorized by NVP intensity levels.

Additional secondary endpoints involve the frequency of maximum treatment guidelines reached, the time of onset and duration of perceived effect after the first dose, and safety through the incidence of adverse events. The degree of therapeutic compliance and patient satisfaction will also be evaluated after 14 days of treatment. Efficacy assessments will be conducted using validated scales such as the NVPQoL and PUQE-24, with data collected at specified timepoints including baseline, day 7, and day 14 of treatment. The trial aims to provide comprehensive insights into the treatment's impact on the quality of life and symptom management in the target population.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Pregnant adult woman aged between 18-45 years (both included).
Patient with gestational age between 5 and 12 weeks (both included: week 5+0 – week 12+6). Gestational age and viability of clinical pregnancy should have been confirmed with ultrasound prior to study inclusion.
Patient presenting with nausea and vomiting of pregnancy (nausea and/or vomiting), of PUQE intensity ≥6.
Patient who has not planned the discontinuation of her pregnancy.
Patient who has signed informed consent to participate in the study and agrees to follow the investigational product's administration instructions and complete all study visits.
Patient who has not previously received Doxylamine/Pyridoxine for the treatment of nausea and vomiting in pregnancy, or alternatively, who has received Doxylamine/Pyridoxine prior to inclusion in the study as long as it has not exceeded a daily dose of 20/20 mg. For this inclusion criterion, the 5 days prior to inclusion in the study will be taken into consideration.

cancel

Exclusion Criteria

Patient who is taking multivitamins or vitamin B6 (pyridoxine) supplements containing more than 10 mg or plans to do so during the study.
A patient who has received an investigational product within 30 days prior to study inclusion, or plans to do so during the course of the study.
Patient who presents difficulty in comprehension, reading or writing, as well as difficulty in following the requirements of the study.
Patient in whom, in the opinion of the investigator, adherence to the prescribed treatment is not expected, sufficient relevant data cannot be available (sociodemographic, clinical, obstetric, nausea and vomiting of pregnancy pathology and/or therapeutic approach), or are not suitable candidates to receive the investigational product or participate in the study.
Patient with trophoblastic disease of gestation.
Patients with nausea and vomiting of etiology other than pregnancy: gastrointestinal pathology, pyelonephritis, vertigo, etc.
Patient previously hospitalized for nausea and vomiting of pregnancy or hyperemesis gravidarum during current pregnancy.
Patient with hypersensitivity to any of the active ingredients or excipients of treatment, or contraindication to treatment with antihistamines (epilepsy, alcoholism, glaucoma, chronic lung disease, etc.).
Patient with a medical condition that results in gastrointestinal malabsorption, such as celiac disease, Crohn's disease, and ulcerative colitis (i.e., may result in low or deficient vitamin B6 levels).
Patients with any contraindication by data sheet to the use of Cariban® 10/10mg (such as, for example, suffering from porphyria, having hypersensitivity to antihistamines, etc.).
Patient treated with other antihistamines, anticholinergics, drugs with anticholinergic activity (e.g. tricyclic antidepressants), dopamine or serotonin antagonists, from the beginning of pregnancy.
Patient who has used ginger or other antiemetic therapy (e.g. acupressure, acupuncture, homeopathy, medical hypnosis, relief bands, etc.) during the past 48 hours or plans to do so during the study.
Patient who is taking oral progesterone or plans to do so during pregnancy.