Assessment of Prednisolone Transfer into Breast Milk and Infant Plasma in Lactating Women with Inflammatory Conditions

The primary objective of this study is to determine the concentration of **prednisolone** in the plasma of breast-fed infants whose lactating mothers are treated with prednisolone. This is clinically relevant as it helps assess the potential exposure and safety of prednisolone in infants, which is crucial for managing inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE), myositis, psoriatic arthritis, and inflammatory bowel disease in breastfeeding mothers.

Secondary objectives include: - Determining the concentration of prednisolone/prednisone in breast milk and maternal plasma, and calculating the milk-to-plasma ratio. This will aid in estimating the average daily infant dose (ADID) and relative infant dose (RID), providing further insight into infant exposure levels. - Evaluating cortisol levels in the infants, which is important for understanding the potential impact of maternal prednisolone treatment on infant adrenal function.

The clinical trial involves a study population consisting exclusively of **female** participants, specifically breastfeeding women aged 18 years and older. The trial focuses on women who are being treated with prednisolone, with doses up to 50 mg/day, for conditions such as **rheumatoid arthritis**, systemic lupus erythematosus (SLE), myositis, psoriatic arthritis, and inflammatory bowel disease. The total number of participants has not been disclosed by the sponsor. Participants were selected based on their treatment with prednisolone and their status as breastfeeding mothers. The trial does not include male subjects and involves a vulnerable population, as it includes both the mothers and their breast-fed infants. Lifestyle considerations such as diet and physical activity are not specified. Key inclusion criteria include the requirement for signed informed consent from both the participating woman and the father of the child. The sponsor has not provided information on the general health status of the participants.

The clinical trial is designed to evaluate the **concentration** of prednisolone in the plasma of breast-fed infants whose mothers are undergoing treatment with prednisolone for conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE), myositis, psoriatic arthritis, and inflammatory bowel disease. This study is a low-intervention cohort trial with biobanking of breast milk and plasma samples. The trial employs a non-randomized, observational design, focusing on the pharmacokinetics of prednisolone transfer into breast milk and subsequently into the infant's plasma. The trial is expected to commence recruitment on February 1, 2024, and conclude by December 31, 2025.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as being a breastfeeding woman treated with prednisolone at doses up to 50 mg/day and being 18 years or older. Informed consent must be obtained from both the mother and the father of the child. The primary endpoint is the measurement of prednisolone concentration in the infant's plasma two hours after breastfeeding, with the feeding occurring one hour post maternal dose intake. Secondary endpoints include the concentration of prednisolone and prednisone in breast milk and maternal plasma, as well as cortisol levels in the infant's blood at the same time point as pharmacokinetic measurements.

The expected duration of participant involvement is aligned with the study's timeline, with specific visits scheduled for sample collection and data analysis. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that compromise the safety of the mother or child. The study ensures that participation does not interfere with the prescribed treatment regimen, maintaining adherence to clinical practice standards. The trial's low-intervention nature is justified by the non-invasive collection of breast milk and blood samples, which are not routinely obtained postpartum, necessitating a clinical trial application.

The clinical trial involves the administration of **betamethasone sodium phosphate**, a chemical compound known for its anti-inflammatory properties. The pharmaceutical form of the medication is identified as PHF00059MIG, and it is administered orally. The maximum daily dose is set at 50 mg, with the same amount being the maximum total dose allowed. The treatment period is limited to one day. The medication is not a pediatric formulation and is not classified as an orphan drug. The active substance is chemically derived, and the trial aims to assess its transfer into human breast milk and the plasma of breastfeeding children.

In addition to the experimental medication, the study may involve the use of standard-of-care therapy as a non-experimental treatment. However, specific details regarding any comparator treatments, placebos, or additional non-experimental therapies are not provided in the available data. Participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed regimen. The primary objective of the trial is to determine the concentration of **prednisolone** in the plasma of breast-fed infants whose mothers are treated with the medication to manage inflammation in various conditions.

Efficacy in this clinical trial will be assessed by measuring the concentration of **prednisolone** in the plasma of breast-fed infants. The primary endpoint is the concentration of prednisolone in the infant's plasma 2 hours after feeding, with the feeding occurring 1 hour following the maternal dose intake. Secondary endpoints include the concentration of prednisolone and prednisone in breast milk and maternal plasma at 1 hour after maternal dose intake, as well as the concentration of cortisol in the infant's blood at the same time point when blood is drawn for pharmacokinetic measurement.

The trial involves collecting breast milk and blood samples to study the excretion of prednisolone into breast milk and its transfer to the child. The study is designed as a low-intervention cohort study, ensuring that participation does not interfere with the treatment prescribed by the participants' physicians. The trial will follow clinical practice procedures, although blood samples from newborns are not routinely taken at 6-8 weeks postpartum, necessitating a clinical trial application. The trial is expected to start recruitment on February 1, 2024, and conclude by December 31, 2025.