Pharmacokinetic Comparison of Subcutaneous Versus Intravenous Paracetamol in Adult Palliative Care Patients

The primary objective of this study is to determine the **pharmacokinetic profile** of subcutaneous paracetamol in patients receiving palliative care and to compare it with the intravenous pharmacokinetic profile in the same patient population. This comparison is clinically relevant as it may provide insights into the optimal route of administration for paracetamol in palliative care settings, potentially influencing pain management strategies and improving patient comfort.

Secondary objectives include evaluating the effectiveness of paracetamol in pain control, assessing the tolerance of the route of administration through skin monitoring (including changes in color, appearance of edema, skin necrosis, and allergic reactions), and monitoring the appearance of pain at the puncture site. Additionally, the study aims to assess the overall tolerance of the treatment. These secondary objectives are crucial for understanding the broader implications of subcutaneous administration in terms of safety and patient experience.

The clinical trial involves **adult patients** over the age of 18 who are undergoing **palliative care**, as defined by the World Health Organization, for conditions that do not respond to curative treatment. Participants must be able to communicate effectively and have a functional central venous line with reflux. They should experience spontaneous pain with a numerical scale rating greater than 3 or have paracetamol as part of their usual treatment regimen. Both male and female subjects are included in the study, and the trial does not specifically target a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the need for participants to be hospitalized, affiliated with the social security system, and capable of self-assessing pain. Additionally, participants must not have contraindications to paracetamol or alternative analgesics and should have recent blood tests indicating no end-stage liver or kidney disease. Informed consent is required for participation.

The clinical trial is designed to evaluate the **pharmacokinetic** profile of subcutaneous versus intravenous administration of **paracetamol** in adult patients undergoing palliative care. This study is structured as a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to run from September 2019 to February 2025, with participant involvement lasting approximately 30 days from the initial screening to the end-of-study visit.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, palliative care status, and the ability to communicate and self-assess pain. Following successful screening, participants will be randomized to receive either subcutaneous or intravenous paracetamol. The primary endpoint involves measuring paracetamolemia to determine pharmacokinetic parameters such as AUC0-t, AUC0-∞, Cmax, Vd, and t1/2 for each mode of administration. Secondary endpoints include pain assessment using a digital scale, skin monitoring, and the collection of adverse events throughout the study period.

Participants will have follow-up visits to monitor safety and efficacy, with systematic collection of adverse events from the signing of consent to day 30. The end-of-study visit will conclude the trial for each participant, with a final assessment of the pharmacokinetic data and overall safety. Conditions that may lead to early termination from the study include the development of contraindications to paracetamol or alternative analgesics, significant adverse events, or withdrawal of consent. The trial aims to provide comprehensive data on the pharmacokinetic differences between the two administration routes in the specified patient population.

The clinical trial involves the administration of **PARACETAMOL B BRAUN 10 mg/ml**, a **solution for infusion**. This pharmaceutical form is specifically designed for intravenous (IV) or subcutaneous (SC) administration. The active substance in this formulation is **paracetamol**, a chemical compound known for its analgesic and antipyretic properties. The maximum daily dose is set at 1 gram, with the same limit for the total dose amount. The treatment period is restricted to a maximum of one day. The product is manufactured by B.BRAUN MELSUNGEN AG and is authorized under the marketing authorization number 34009 583 081 2 3 in France. The product is classified under the ATC code N02BE01, indicating its role as a non-opioid analgesic.

In this study, the primary objective is to determine the pharmacokinetic profile of subcutaneous paracetamol in patients receiving palliative care and to compare it with the intravenous pharmacokinetic profile in the same patient population. The trial does not involve any pediatric formulations or orphan drug designations. The study is designed to ensure participant compliance through careful monitoring of dosing schedules and administration routes. No additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial protocol.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint involves the measurement of **paracetamolemia** to determine pharmacokinetic parameters such as AUC0-t, AUC0-∞, Cmax, Vd, and t1/2 for each mode of administration (subcutaneous versus intravenous) in the same patient. Pharmacokinetic curves will be generated to facilitate this comparison. Secondary endpoints include the assessment of pain using a digital scale, as well as skin monitoring and tolerance assessment throughout the administration period and protocol completion, from Day 0 to Day 30. Additionally, safety will be evaluated by systematically collecting adverse events of any grade, as per the CTCAE scale, from the signing of consent to Day 30, which is the minimum follow-up period for drug research. These efficacy parameters will be collected and analyzed according to the specified schedule to ensure comprehensive evaluation of the treatment's impact.