Adhesion and Safety of Rotigexole Compared to Neupro®

Study Design: A non-inferiority open-labelled crossover randomized controlled trial, of two arms, to investigate the adhesiveness and safety of Rotigexole 8 mg/24 hours transdermal patch, manufactured by Eva pharma, Egypt, compared to the innovator product, Neupro® 8 mg/ 24 hours transdermal patch, manufactured by UCB Pharma S.A., Belgium, after 24 hours of application.

Planned Treatment Duration per Subject and Study Duration per Subject:

The overall duration of the study preparation and study conduction is 7 weeks and 5 days (54 days) that are scheduled as follows:

1. Preparatory Phase of the Study: Patients Screening (2 weeks):

Patient screening for eligibility will occur over 14 days. During this time, all relevant administrative, demographic data collection, and informed consent will be conducted for eligible patients. 2. Run-in-Phase (3 weeks):

* On the first day of the run-in phase, prior to drug administration, comprehensive physical and laboratory re-assessments will be conducted to document the initial patient's systemic status which will be monitored throughout the study to observe any potential systemic alterations for ethical purposes. * The transdermal patch Rotigotine (Neupro ®) only will be applied in the run-in phase in a dose taper manner on weekly basis according to the European Medicines Agency (1) and the US FDA (2) recommendations for treating cases of PD. A starting dose of 4 mg/24 h initially, increasing in weekly increments of 2 mg/24 h (based on clinical response and tolerability) to a maximum of 8 mg/24 h; starting dose of 4 mg/24 h in the 1st week will be applied followed by 6 mg/24 h in the 2nd week and finally 8 mg/24 h in the 3rd week. * The patch should be applied on clean, dry, healthy skin on the abdomen (tummy), thigh, hip, side, shoulder or upper arm. * A Rotigotine transdermal patch necessitates daily replacement as the drug delivery lasts for 24 hours only (3-5). Notably, re-application at the same site should be avoided for 14 days. * Comprehensive physical and laboratory assessments will be re-evaluated at the last day of the run-in-phase and prior to the commencement of the following intervention phase. 3. Intervention Phase of the Study:

* This phase will last for five days only. * At this phase patients will be randomly assigned to sequence of TRTR or RTRT (T=Test=Rotigexole, R=Reference= Neupro ®). Each transdermal patch, either T or R, will be replaced at the same time every 24 hours. * Patients will receive accommodation for four nights during the intervention period to assess adhesion. Adhesion assessments will occur at 4, 8, 12 and 24 hours in accordance with FDA guidelines for transdermal patch evaluation. * The application of the transdermal patches should be on different sites of the same region "abdomen (tummy), thigh, hip, side, shoulder or upper arm". * Subjects must refrain from using topical products on the skin area designated for TDS application due to potential effects on adhesion. Additionally, hair at the application site should be clipped rather than shaved. * The alternating transdermal patch should then be applied on the same site of the same region on the contralateral side. * During this period, the patient is allowed to practice his or her routine activities without any restrictions in movement. * Assessments will be performed just after application and will be repeated at 4, 8, 12 and 24 hours * Patch reinforcement such as over-taping should be avoided. * At each assessment, photographic documentation of TDS adhesion to the skin must be archived. This documentation serves to corroborate the visual evaluation of adhesion percentages recorded at each time point. * At the final assessment of the 2nd transdermal patch application, the patient will be prescribed an alternative medicament (Ramixole) to stabilize the patient's conditions. 4. Post-intervention Phase:

* All participants will undergo a comprehensive re-evaluation two weeks post-study to identify any systemic alterations for safety and ethical considerations (one follow-up visit). * Any arising adverse systemic conditions in patients will be appropriately managed

• Proportion of participants achieving more than 90% adherence at 4, 8, 12 and 24 hours at each period as assessed by the investigator/designee as per modified EMA scale for adhesion. [Time frame: two treatment periods (4 days)]
• Adjusted Mean adherence percentage at each assessment time (4, 8, 12 and 24 hours). [Time frame: two treatment periods (4 days)]
• Proportion of participants with a meaningful degree of detachment (more than half of the patch lifting off the skin or falling off) at 4, 8, 12 and 24 hours. [Time frame: two treatment periods (4 days)]
• Number of patches that are completely detached at 4, 8, 12 and 24 hours. [Time frame: two treatment periods (4 days)]
• Number of participants with cold flow in each treatment period (Cold flow is defined as dark ring formed around the patch). [Time frame: two treatment periods (4 days)]
• Number of participants with patch movement/displacement in each treatment period. [Time frame: two treatment periods (4 days)]
• Number of participants with patch wrinkling in each treatment period. [Time frame: two treatment periods (4 days)]
• Number of participants with patch residue formation in each treatment period (Patch residue formation is assessed at patch application on the release liner and at patch removal on the skin). [Time frame: two treatment periods (4 days)]
• % of patients reporting ease or difficulty in patch application and removal. [Time frame: two treatment periods (4 days)]
• Frequency of Adhesion-Related Issues: Evaluate the frequency of adhesion-related issues (e.g., patch detachment). [Time frame: two treatment periods (4 days)]
• % of patients with reported interference in daily activities due to patch adhesion. [Time frame: two treatment periods (4 days)]
• % of patients reporting overall satisfaction with wearing each patch type, measured using a Patch Wear Satisfaction Scale. [Time frame: two treatment periods (4 days)]