A prospective, multicentre open-label clinical trial to evaluate the efficacy of the fixed-dose combination of Doxylamine and Pyridoxine 10/10 mg modified-release capsules on the quality of life of pregnant women presenting with nausea and vomiting of pregnancy (NVP)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Itf Research Pharma S.L.

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

31 Oct 2023 → 13 Aug 2024

Decision date (initial)

2023-09-12

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of treatment with the fixed combination of doxylamine/pyridoxine 10/10 mg modified-release hard capsules after 14 days of administration on the quality of life of pregnant women with nausea and vomiting of pregnancy

Secondary objectives 9

1. To evaluate the efficacy of treatment with the fixed combination of Doxylamine/Pyridoxine 10/10 mg modified-release capsules on the quality of life of pregnant women with nausea and vomiting of pregnancy after 7 days of administration.
2. To evaluate the efficacy of treatment with the fixed combination of doxylamine/pyridoxine 10/10 mg modified-release capsules on the quality of life of pregnant women with nausea and vomiting of pregnancy between 7 and 14 days of administration.
3. To evaluate the efficacy of treatment with the fixed combination of Doxylamine/Pyridoxine 10/10 mg modified-release capsules on nausea and vomiting of pregnancy, on a daily basis, throughout the study.
4. Describe the maximum guidelines achieved after 14 days of treatment, as well as the patient profile associated with each regimen, and the time taken to reach the maximum regimen.
5. To evaluate the time of onset and duration of effect perceived by the patient after the first administration of the fixed combination of doxylamine/pyridoxine 10/10 mg modified-release capsules.
6. To evaluate the safety of doxylamine/pyridoxine 10/10 mg modified-release capsules during treatment.
7. To evaluate the therapeutic compliance by patient and by regimen used, after 14 days of treatment.
8. To evaluate patient satisfaction with treatment with doxylamine/pyridoxine 10/10 mg modified-release capsules after 14 days of administration.
9. To evaluate investigator satisfaction with treatment with doxylamine/pyridoxine 10/10 mg modified-release capsules after 14 days of administration.

Conditions and MedDRA coding

Nausea and vomiting of pregnancy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Pregnant adult woman aged between 18-45 years (both included).
2. 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.
3. Patient presenting with nausea and vomiting of pregnancy (nausea and/or vomiting), of PUQE intensity ≥6.
4. Patient who has not planned the discontinuation of her pregnancy.
5. 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.
6. 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.

Exclusion criteria 13

1. Patient who is taking multivitamins or vitamin B6 (pyridoxine) supplements containing more than 10 mg or plans to do so during the study.
2. 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.
3. Patient who presents difficulty in comprehension, reading or writing, as well as difficulty in following the requirements of the study.
4. 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.
5. Patient with trophoblastic disease of gestation.
6. Patients with nausea and vomiting of etiology other than pregnancy: gastrointestinal pathology, pyelonephritis, vertigo, etc.
7. Patient previously hospitalized for nausea and vomiting of pregnancy or hyperemesis gravidarum during current pregnancy.
8. 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.).
9. 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).
10. 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.).
11. Patient treated with other antihistamines, anticholinergics, drugs with anticholinergic activity (e.g. tricyclic antidepressants), dopamine or serotonin antagonists, from the beginning of pregnancy.
12. 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.
13. Patient who is taking oral progesterone or plans to do so during pregnancy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in results in the global score of the NVPQoL scale after 14 days of treatment with Doxylamine/Pyridoxine 10/10 mg modified-release capsules versus baseline.

Secondary endpoints 10

1. Difference in results versus baseline, after 7 days of treatment with Doxylamine/Pyridoxine 10/10 mg modified release capsules in the NVPQoL score. The overall score will be evaluated.
2. Difference in results between 7 and 14 days of treatment with Doxylamine/Pyridoxine 10/10 mg modified-release capsules in the NVPQoL score. The overall score will be evaluated.
3. Evolution of nausea and vomiting during treatment with the fixed combination of Doxylamine/Pyridoxine 10/10 mg capsules. The evolution will be evaluated daily against baseline, as well as between 7 and 14 days of treatment by: • PUQE-24 global score • Frequency and score of the individual items of the PUQE-24 scale: nausea, vomiting and retching • Frequency of subjects without NVP (PUQE-24=3), with NVP mild intensity (PUQE-24=4-6), moderate (PUQE-24=7-12) or severe (PUQE-24=13-15).
4. Frequency of maximum treatment guidelines reached after 14 days of treatment, according to the titration reflected in the summary of product characteristics of the investigational product (morning-afternoon-night posology: 0-0-2, 1-0-2, or 1-1-2) and time taken to achieve the maximum regimen.
5. Time of onset and duration of perceived effect (hours) after taking the first dose (Day 1) of the fixed combination of Doxylamine/Pyridoxine 10/10 mg modified-release capsules, assessed by questionnaire to the patient.
6. Safety, through the incidence of adverse events and serious adverse events during the study period.
7. Degree of therapeutic compliance categorized as poor (<50%), moderate (≥50% to <75%), good (≥75% to <90%) and very good (≥90%), per patient, and by regimen, after 14 days of treatment, obtained by evaluation of excess medication according to the regimen used during the 14 days of treatment.
8. Degree of patient satisfaction, categorized as excellent, very good, good, fair, bad and not evaluated after 14 days of administration.
9. Degree of satisfaction of the investigator, defined in the same way as criterion 8.
10. The profile of the patient (sociodemographic and baseline clinical characteristics) will also be described according to the maximum pattern reached.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Itf Research Pharma S.L.

Sponsor organisation

Itf Research Pharma S.L.

Address

Calle De San Rafael 3, Poligono Industrial Calabozos Poligono Industrial Calabozos

City

Alcobendas

Postcode

28108

Country

Spain

Scientific contact point

Organisation

Itf Research Pharma S.L.

Contact name

Dra. Tatiana Vilchez Quino

Public contact point

Organisation

Itf Research Pharma S.L.

Contact name

Dra. Tatiana Vilchez Quino

Third parties 1

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications