Evaluation of Promethazine Hydrochloride on Bimanual Coordination in Healthy Volunteers Under Altered Gravitational Conditions

The primary objective of this study is to evaluate the effects of **promethazine** and altered gravity on bimanual coordination. Specifically, the study aims to:

• Generate dose-response relationships between bimanual coordination operational variables as a function of g-levels.
• Assess whether repeated exposure to altered g-levels impacts performance on bimanual coordination tasks.
• Determine if promethazine influences operational performance in bimanual coordination tasks during various g-levels and during rapid g-level transitions experienced in parabolic flight.

This research is clinically relevant as it explores the physiological impacts of altered gravity and pharmacological intervention on motor coordination, which could have implications for understanding human performance in environments with variable gravitational forces, such as space travel.

The clinical trial involves **healthy volunteers** aged between 18 and 55 years, comprising both male and female participants. The study population is characterized by individuals with a body mass index (BMI) of less than 30, indicating non-obese subjects. Participants are required to be affiliated with a Social Security system, and non-French residents must hold a European Health Insurance Card (EHIC) or a Global Health Insurance Card (GHIC). All participants have undergone a medical examination akin to a standard aviation medical examination for private pilot aptitude, specifically the JAR FCL3 Class 2 medical examination. Additionally, participants are right-hand dominant, as determined by a Laterality Quotient Score of +60 or higher on the Edinburgh Handedness Questionnaire. The sponsor has not provided information regarding the total number of participants in the trial. The trial does not include a vulnerable population, and the selection criteria ensure that participants are capable of providing informed consent and are willing to partake in the study.

The clinical trial is designed to evaluate the effects of **promethazine** on bimanual coordination under altered gravity conditions. This study is a randomized, double-blind, controlled trial involving healthy volunteers aged 18-55 with a body mass index (BMI) of less than 30. Participants must be right-hand dominant and have passed a medical examination similar to a standard aviation medical examination for private pilot aptitude. The trial is categorized as low-intervention due to the authorized use of **promethazine** and minimal additional risk to participants compared to normal clinical practice.

The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria, including written informed consent. Participants will be randomly assigned to receive either **PHENERGAN 25 mg** or a placebo, both administered orally in the form of coated tablets. The maximum daily dose of **promethazine** is 25 mg, with a total dose not exceeding 50 mg over a maximum treatment period of four days. The primary endpoint is the assessment of bimanual coordination performance, measured by harmonicity during various g-levels and rapid g-level transitions.

Study visits will include baseline assessments, administration of the investigational product, and performance evaluations during parabolic flight to simulate altered gravity conditions. Follow-up visits will monitor the participants' response to the treatment and any adverse effects. The trial is expected to last until June 2024, with participant involvement spanning the duration of the treatment period and follow-up assessments. Early termination from the study may occur if participants experience significant adverse effects or withdraw consent.

The clinical trial involves the administration of **PHENERGAN 25 mg**, a coated tablet containing the active substance **promethazine hydrochloride**. This medication is manufactured by Laboratoires Frilab and is authorized in France. The pharmaceutical form is a coated tablet, and the route of administration is oral. The dosage regimen for PHENERGAN is a maximum daily dose of 25 mg, with a total maximum dose of 50 mg over the treatment period. The treatment period is limited to a maximum of 4 days. The primary objective of the trial is to assess the effects of promethazine on bimanual coordination tasks under various gravitational conditions.

In addition to the experimental medication, a **placebo** is used as a comparator in the study. The placebo is a tablet marketed by Centrelab under the reference f00199. The composition of the placebo includes 244.4 mg of dihydrated calcium hydrogen phosphate, 13 mg of corn starch, and 2.6 mg of magnesium stearate. The placebo is administered orally, mirroring the administration route of the experimental medication, to ensure blinding and maintain the integrity of the study design. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint of **bimanual coordination performance**, which will be measured using the parameter of harmonicity. The trial aims to determine the effects of promethazine on operational performance in bimanual coordination tasks under various gravitational levels, including during rapid transitions experienced in parabolic flight. The assessment of bimanual coordination will be conducted through specific tasks designed to test the participants' performance, with harmonicity serving as the key metric for evaluating coordination efficacy. The trial will generate dose-response relationships and assess the impact of repeated exposure to altered gravitational levels on task performance. The study is categorized as a low-intervention clinical trial, as the investigational medicinal product, Phenergan, is authorized and its use is supported by scientific evidence regarding its safety and efficacy. The monitoring procedures are designed to ensure minimal additional risk or burden to participants compared to standard clinical practice.