MORPHINE PHARMACOKINETICS AND –DYNAMICS IN HEALTHY VOLUNTEERS AND PATIENTS WITH OBESITY AND OBSTRUCTIVE SLEEP APNOEA. -AN INVESTIGATOR INITIATED, CLINICAL STUDY OF THE IMPACT OF OBESITY AND SLEEP APNOEA ON THE PHARMACOLOGY OF MORPHINE

The primary objective of this clinical study is to generate significant insights into the **safety** and **efficacy** of **morphine** for perioperative pain management, particularly in bariatric patients with **obstructive sleep apnoea** undergoing bariatric surgery. This is clinically relevant as it aims to optimize pain management strategies, ensuring effective pain relief while minimizing adverse effects, which is crucial for improving patient outcomes in this specific population. Additionally, the study seeks to enhance understanding of the pharmacokinetics and pharmacodynamics of morphine, a first-line drug for acute pain relief, to support a more personalized approach to acute peri- and postoperative pain treatment.

The clinical trial involves participants diagnosed with **obesity** and **obstructive sleep apnoea**. The study population includes both male and female subjects, with an age range corresponding to category code 3, which typically represents adults. The trial does not specifically target a vulnerable population. Participants were selected based on the presence of obesity and obstructive sleep apnoea, as these are the principal inclusion criteria. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. The trial aims to gather significant insights into the safety and efficacy of morphine for perioperative pain management, particularly in bariatric patients undergoing surgery.

The clinical trial is designed to evaluate the **pharmacokinetics** and **pharmacodynamics** of **morphine hydrochloride** in individuals with obesity and obstructive sleep apnea. This is a Phase 4, randomized, double-blind, controlled study aimed at understanding the impact of these conditions on morphine's efficacy and safety, particularly in the context of perioperative pain management. The trial is expected to run from October 2022 to January 2025, with participant involvement lasting up to one month. The study will include a series of visits, beginning with a screening visit to assess eligibility based on criteria such as the presence of obesity and obstructive sleep apnea.

Participants will be randomly assigned to receive either the test drug or a control, with **naloxone hydrochloride** and **lidocaine hydrochloride** serving as auxiliary medications. The trial will employ a double-blind methodology to ensure unbiased results. The primary endpoints include the area under the curve (AUC) and maximum plasma concentration (CMAX) of morphine, while secondary endpoints involve quantitative sensory testing through various stimulus intensity assessments. Study visits will be scheduled to monitor these parameters, with follow-up visits to assess ongoing safety and efficacy.

The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted. Participants may be withdrawn from the study early if they experience adverse effects or if they no longer meet the inclusion criteria. The trial aims to provide insights into a more personalized approach to pain management, minimizing side effects while ensuring effective pain relief. The study's findings are anticipated to benefit future surgical patients, particularly those undergoing bariatric surgery. The trial's design and procedures adhere to rigorous scientific standards to ensure the reliability and validity of the results.

The clinical trial involves the administration of **Naloxone Hydrochloride**, which is utilized as an **antidote**. This experimental medication is provided in the form of an **injection**. The administration routes include **intravenous (IV) injection** and **IV infusion**. The maximum daily dose is set at 4 mg, with a total maximum dose of 10 mg over the treatment period. The treatment duration is limited to one day. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol.

**Lidocaine Hydrochloride** is employed as a **local anaesthetic** in this study. It is also administered in the form of an **injection**, specifically via the **subcutaneous route**. The maximum daily and total dose is 100 mg, with the treatment period restricted to one day. Monitoring of participant compliance will be conducted to ensure proper administration and adherence to the dosing regimen.

The primary focus of the trial is on **Morphine Hydrochloride**, which serves as an **analgesic**. This medication is administered in the form of an **injection**, with routes including **IV injection** and **IV infusion**. The maximum daily and total dose is 15 mg, with a treatment period of one day. Compliance with the dosing schedule will be closely monitored to ensure accurate administration and adherence to the study protocol.

The efficacy of **morphine hydrochloride** in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the area under the curve (AUC) for morphine and the maximum plasma concentration (CMAX) of morphine. These parameters will provide insights into the pharmacokinetics of morphine in the study population, which includes healthy volunteers and patients with obesity and obstructive sleep apnea. The secondary endpoints involve the reported stimulus intensity during quantitative sensory testing, which includes Heat, Cold, Bone, and Muscle Pressure Tests. This will help evaluate the pharmacodynamics of morphine, focusing on its efficacy in pain relief.

The trial aims to generate important knowledge on the safety and efficacy of morphine for perioperative pain management, particularly in bariatric patients with obstructive sleep apnea undergoing surgery. The study will contribute to a more personalized approach to acute peri- and postoperative pain treatment, aiming to deliver effective pain relief with minimal side effects. The trial is categorized as a Phase 4 study, indicating it is conducted after the drug has been approved for use, to gather additional information on its efficacy and safety in specific populations.