A Randomized, Double-Blind Study on Intravenous Propofol Injection Pain Versus Placebo in Healthy Adults

The primary objective of this randomized, double-blind parallel group study is to determine the proportion of participants experiencing significant **pain** following intravenous injection of **propofol** or placebo. This is clinically relevant as it aims to quantify and compare the pain associated with propofol injections, which is a common concern in clinical settings where propofol is used as an anesthetic agent.

Secondary objectives include:

• Determining pain intensity by intravenous injection of propofol or placebo.
• Assessing pain intensity retrospectively scored after the procedure.
• Evaluating the temporal evolution of pain intensity following intravenous injection of propofol/placebo.
• Measuring pain intensity during and after the insertion of the intravenous cannula.
• Determining the level of sedation after cuff pressure release.

The clinical trial focuses on evaluating the **pain** response in participants following an intravenous injection of propofol or placebo. The study population includes both male and female subjects, aged between 18 and 49 years, who are overtly healthy as determined by medical evaluation, including medical history and physical examination. The trial does not involve a vulnerable population. Participants are required to have a negative highly sensitive urine pregnancy test if they are women of childbearing potential. The sponsor has not provided information regarding the total number of participants involved in the study. Participants were selected based on their health status and age, ensuring they meet the inclusion criteria. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the incidence of pain associated with the intravenous injection of **propofol** compared to a placebo in healthy adult participants. The trial will involve a parallel group design, ensuring that participants are randomly assigned to receive either the active treatment or the placebo, with neither the participants nor the investigators aware of the group assignments. The study is set to commence recruitment on August 4, 2025, and is expected to conclude by December 31, 2028, encompassing a total duration of approximately three years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as being overtly healthy, aged between 18 and 50 years, and having a negative pregnancy test for women of childbearing potential. Following successful screening, participants will be enrolled in the trial and will attend subsequent visits for the administration of the study drug or placebo and for the collection of primary and secondary endpoint data. The primary endpoint is the proportion of participants experiencing significant pain, as measured by a Visual Analog Scale (VAS) score of 30 mm or higher. Secondary endpoints include maximum VAS pain, maximum Numeric Rating Scale (NRS) pain, and other pain-related metrics.

The expected length of participant involvement is determined by the maximum treatment period, which is one day for the **propofol** group and two days for the **saline** placebo group. Participants may be withdrawn from the study early if they experience adverse events, fail to comply with study procedures, or withdraw consent. The end-of-study visit will involve a final assessment to ensure participant safety and to collect any remaining data. The trial is conducted under the guidelines of a Phase 4 clinical trial, focusing on the safety and efficacy of the intervention in a real-world setting.

The clinical trial involves the administration of two treatments: **Propolipid** and **saline**. **Propolipid** is an emulsion for injection/infusion containing the active substance **propofol**. It is manufactured by Fresenius Kabi Norge AS and is identified by the EU medicinal product number PRD534193. The pharmaceutical form is an emulsion, and it is administered via intravenous bolus use. The maximum daily dose is 40 mg, with a total maximum dose of 40 mg over a treatment period of one day. The role of **Propolipid** in the trial is as the test medication, and it is not a pediatric formulation.

The comparator treatment in this study is **saline**, which serves as the placebo. **Saline** is provided as a solution for injection and is administered via intravenous bolus use. The maximum daily dose is 50 ml, with a total maximum dose of 50 ml over a treatment period of two days. **Saline** is not a pediatric formulation and does not have a marketing authorization number. It is identified by the EU medicinal product number SUB20722. The role of **saline** in the trial is as the placebo, and it is used to compare the pain experienced during the injection of **Propolipid**.

Both treatments are administered under controlled conditions to ensure participant safety and compliance. The trial is designed to assess the proportion of participants experiencing significant pain upon intravenous injection of either **propofol** or placebo. Compliance with dosing schedules is monitored throughout the study to maintain the integrity of the trial results.

Efficacy in this clinical trial will be assessed by evaluating the proportion of participants experiencing significant pain during the intravenous injection of **propofol** or placebo. The primary endpoint is the proportion of participants with a Visual Analog Scale (VAS) score of 30 mm or higher on a 0-100 mm scale. Secondary endpoints include the maximum electronic VAS pain score, maximum Numeric Rating Scale (NRS) pain score, time to maximum electronic VAS pain, area under the curve (AUC) for different time intervals (0-1 min, 1-2 min, 2-3 min), AUC for VAS scores of 30 or higher, the curve shape of electronic VAS pain by description of the curve (number of peaks), and the Richmond Agitation-Sedation Scale (RASS).

The efficacy parameters will be measured using validated scales such as the electronic VAS and NRS. The collection and analysis of these parameters will occur at specified timepoints, including the immediate period following the injection to capture the peak pain response and its progression over time. The data will be analyzed to determine the proportion of participants experiencing significant pain and to evaluate the pain intensity and duration associated with the injection of **propofol** compared to placebo.