A Study of Prucalopride in Breastfeeding Women With Constipation

Study Overview
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Brief Summary
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Prucalopride is a medicine used to treat constipation. The main aim of the study is to measure prucalopride concentrations in breast milk. Other aims are to check the growth and development of babies breastfed by their mothers who took prucalopride and to check if the babies had any side effects. During the study, participants will provide one set of milk samples over 24 hours using an electric breast pump. Breast milk samples will be collected at home and will be shipped to the laboratory. Also, participants will be asked questions during telephone interviews every 2 months in the first year of their baby's life. They will also be asked to complete growth and development questionnaires about their baby.

Official Title
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A Breast Milk Study in Lactating Women Who Have Been Prescribed Therapeutic Doses of MOTEGRITY® or RESOTRAN® (Prucalopride) for Chronic Idiopathic Constipation to Evaluate Prucalopride Concentrations in Breast Milk, and to Collect Incidental Safety Data From the Nursing Infants

Conditions
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Chronic Constipation

Intervention / Treatment
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* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants cannot be enrolled before all inclusion criteria are confirmed. Female participants with an ability to voluntarily provide verbal followed by written, signed, and dated (personally or via a legally authorized representative) informed consent as applicable to participate in the study. Participants greater than or equal to (>=) 18 years of age at the time of consent. This inclusion criterion will only be assessed at the time of enrollment. Participants who are currently breastfeeding a singleton infant who is between 10 days and 11 months 0 days. Note that participants pumping breast milk and bottle feeding their infant breast milk are allowed to participate. Participants who are currently exclusively breastfeeding or breastfeeding with supplemental formula and/or solid food. Infants who are exclusively breastfed and do not eat solid food are preferred. Participants who are currently treated as prescribed by their physician with MOTEGRITY or RESOTRAN (generic forms of prucalopride not allowed) for functional constipation, including chronic idiopathic constipation (CIC) and irritable bowel syndrome-constipation (IBS-C), for at least 5 consecutive days at the time of taking the first breastmilk sample. Participants who agree to the conditions and requirements of the study including the sample collection, interview schedule, completion of developmental questionnaires, and release of medical records. Participants with an understanding, ability, and willingness to fully comply with study procedures and restrictions. Exclusion Criteria: The participant will be excluded from the study if any of the following exclusion criteria are met: Participants who are breastfeeding an infant who: is hospitalized, has a major birth defect, or has a history of a disease that could affect absorption or drug disposition. Participants who have used MOTEGRITY or RESOTRAN while breastfeeding for a condition other than functional constipation. Participants who are pregnant at the time of enrollment. Participants who have started to wean their child from breast milk. Participants with a history of any hematological, hepatic, respiratory, cardiovascular, renal, gall bladder removal, or other current or recurrent disease that could affect the action, absorption, or disposition of prucalopride.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| All Study Participants<br>Participants with chronic idiopathic constipation who are treated with prucalopride 2 milligrams (mg) oral tablets which was initiated prior to enrollment, and are breastfeeding their infant at the time of enrollment and sample collection will be observed prospectively. | Other: No Intervention<br>* This is a non-interventional study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Milk Concentration-time Curve (AUCmilk) of Prucalopride | AUCmilk will be derived from a series of 7 timed, full expression breast milk samples collected from a single breast using an electric breast pump over a 24-hour period for breast milk prucalopride concentrations. | Pre-dose, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 1 | 
| Average Concentration of Prucalopride in Milk | Average concentration will be derived from a series of 7 timed, full expression breast milk samples collected from a single breast using an electric breast pump over a 24-hour period for breast milk prucalopride concentrations. | Pre-dose, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 1 | 
| Time Interval Over Which the AUCmilk Measured | Time interval over which the AUCmilk is measured will be reported. | Pre-dose, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Infant Dosage | Daily prucalopride dose will be received by the infant through breastfeeding. | Pre-dose, 1, 2, 4, 8, 12, and 24 hours post-dose | 
| Weight-adjusted Percentage of the Maternal Dose | Percentage maternal dose will be calculated as (infant dose [mg/kg/day]/maternal dose [mg/kg/day])*100. The weight-adjusted percentage of the maternal dose (also called the relative infant dosage [RID]) consumed in breast milk over 24 hours will be reported. | Up to 24 hours post-dose | 
| Number of Infants With Adverse Events (AEs) Based on Maternal Report | Number of infants with AEs while being breastfed by a mother who is taking prucalopride will be obtained by maternal report (by phone). | Up to 1 year of age | 
| Change in Length During the First Year of Life in Infant's | Growth changes in length in centimeters every 2 months during the first year of life in infant's breastfed by mothers taking prucalopride will be obtained by maternal report (by phone), and medical records abstraction. | Up to 1 year of age | 
| Change in Weight During the First Year of Life in Infant's | Growth changes in weight in grams every 2 months during the first year of life in infant's breastfed by mothers taking prucalopride will be obtained by maternal report (by phone), and medical records abstraction. | Up to 1 year of age | 
| Infant's Neurodevelopmental Performance Based on Ages and Stages Questionnaire-3 (ASQ-3) | Infant's neurodevelopmental progress at 4 and 12 months will be assessed by the ASQ-3 which will be completed by the mother. The ASQ-3 is a developmental screening instrument with 5 domains: (i) personal-social, (ii) gross motor, (iii) fine motor, (iv) problem solving, and (v) communication. Each domain has 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. ASQ-3 average = average score of 5 aspects. | Up to 1 year of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prucalopride, Motegrity, Pharmacokinetics, Lactation, Breastfeeding, Milk-only study, Infant growth and development, Infant neurodevelopment, Infant outcomes