Evaluation of Safety, Tolerability, and Analgesic Efficacy of Intranasal Ketamine Hydrochloride and Sufentanil Citrate in Pediatric Patients with Moderate to Severe Pain

The primary objective of this study is to assess the **safety** and **tolerability** of CT001, a nasal spray solution containing ketamine hydrochloride and sufentanil citrate, in pediatric participants experiencing moderate to severe pain in an acute care setting. Additionally, the study aims to evaluate the **analgesic effect** of CT001 in this population. These objectives are clinically relevant as they address the need for effective and safe pain management strategies in pediatric patients, a group that often requires specialized treatment considerations.

Secondary objectives include:

• Assessing medication errors in pediatric participants with moderate to severe pain in an acute care setting.
• Evaluating the additional analgesic effect of CT001 in this population.
• Determining the need for supplemental analgesics.
• Evaluating the feasibility of CT001 in pediatric participants with moderate to severe pain in an acute care setting.

The clinical trial involves a total of **75 participants** who are pediatric patients aged between **1 year to 17 years**. The study population includes both **male and female** subjects who are attending an Emergency Department following an injury and experiencing **acute pain** of moderate to severe intensity. Participants were selected based on their attendance at an emergency setting and the intensity of their pain, which is measured using age-appropriate pain scales. The trial specifically targets a vulnerable population, given the pediatric nature of the participants. Informed consent was obtained from parents or guardians, with assent from the child when possible and relevant, depending on age. The study does not specify any particular lifestyle considerations such as diet or physical activity, focusing instead on the acute care context and the immediate health status related to pain management.

The clinical trial is designed as an open-label, prospective study to evaluate the **safety**, tolerability, and analgesic effect of a nasal spray solution containing **ketamine hydrochloride** and **sufentanil citrate** in pediatric patients experiencing moderate to severe pain in an acute care setting. The trial is categorized as a Phase 4 study and is not considered low intervention. The study aims to assess the primary endpoint of analgesic efficacy by measuring changes in pain intensity from baseline using age-appropriate scoring instruments, such as the FLACC score, Wong-Baker FACES scale, and the 0-10 Numerical Rating Scale (NRS). Secondary endpoints include the maximum change in pain intensity within 30 minutes post-administration, the proportion of participants achieving a 30% reduction in pain intensity, and the number of children requiring additional analgesics.

The trial is expected to commence recruitment on December 1, 2023, and conclude by December 31, 2024. Participants will be involved in the study for a maximum treatment period of one day, with a maximum daily dose of 600 microliters of the investigational medicinal product (IMP). The study will include an initial screening visit to confirm eligibility, followed by the administration of the IMP and subsequent monitoring of pain intensity at specified intervals (10, 15, 20, 30, 45, and 60 minutes post-administration). The end-of-study visit will occur after the final pain assessment, ensuring all data is collected and any adverse events are documented.

Inclusion criteria for the study require participants to be pediatric patients aged 1 to 17 years, attending an emergency department following an injury, and experiencing acute pain of moderate or severe intensity. Informed consent must be obtained from a parent or guardian, with assent from the child when applicable. There are no specified exclusion criteria provided. Participants may be withdrawn from the study if they experience significant adverse events or if they do not adhere to the study protocol. The trial's design and procedures are structured to ensure the collection of reliable data while maintaining the safety and well-being of the participants.

The clinical trial involves the administration of an **experimental medication** identified as CT001, which is a **nasal spray solution** containing the active substances **ketamine hydrochloride** and **sufentanil citrate**. This investigational product is designed for use in pediatric patients experiencing moderate to severe pain in an acute care setting. The pharmaceutical form of the medication is a nasal spray, and it is administered via the nasal route. The maximum daily dose is 600 microliters, with the same amount being the maximum total dose allowed during the treatment period, which is limited to one day. The formulation is not specifically designed for pediatric use, but it is being tested in this population to assess its safety, tolerability, and analgesic efficacy.

In this study, no **non-experimental treatments** such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on evaluating the effects of the CT001 nasal spray. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol. The trial aims to provide insights into the feasibility of using this combination of active substances for pain management in children, with a particular emphasis on safety and tolerability.

Efficacy in this clinical trial will be assessed by evaluating the **analgesic effect** of the investigational product, CT001, in pediatric patients experiencing moderate to severe pain in an acute care setting. The primary endpoint for efficacy assessment is the change in pain intensity from baseline, measured using age-appropriate scoring instruments. For participants aged 1 to less than 5 years, the FLACC score will be utilized. The Wong-Baker FACES scale will be applied for those aged 5 to less than 9 years, and the 0-10 Numerical Rating Scale (NRS) will be used for participants aged 9 years and above.

Secondary endpoints include the maximum change in pain intensity within 30 minutes post-administration of the investigational medicinal product (IMP), the number and proportion of participants achieving a 30% reduction in pain intensity within 30 minutes, and changes in pain intensity at various timepoints: 10, 15, 20, 30, 45, and 60 minutes post-IMP. Additionally, derived variables such as the area under the curve (AUC), peak change in pain intensity, and duration of effect will be calculated from the recorded pain assessments. The number of children receiving additional analgesics will also be assessed at specified timepoints.