Phase 3 Randomized Multicentric Open-Label Study of Capsaicin Patch vs. Oral Duloxetine in Chemotherapy-Induced Peripheral Neuropathy

The primary objective of this study is to demonstrate that a **capsaicin** 179 mg patch, when compared to daily **duloxetine**, improves painful chemotherapy-induced peripheral neuropathy (CIPN) after a 5-week treatment period. This is clinically relevant as CIPN is a common and debilitating side effect of chemotherapy, and effective management can significantly enhance patient quality of life and treatment adherence.

Secondary objectives include:

• To assess safety.
• To evaluate the efficacy on non-painful sensory symptoms.
• To assess the improvement in quality of life using QLQ C30 and SF12.
• To assess interference with daily function.
• To assess the global improvement of CIPN.
• To assess global satisfaction using PGIC.
• To evaluate the efficacy and safety of repeated application of the capsaicin 179 mg patch.
• To measure the psychometric properties of the QLQ CIPN20 French version.

The clinical trial focuses on participants diagnosed with **chemotherapy-induced peripheral neuropathy** (CIPN), characterized by painful symptoms such as numbness, tingling, or burning pain in a "gloves and socks" distribution following neurotoxic chemotherapy. The study population includes both male and female subjects aged 18 years and older. Participants are required to have stable doses of concomitant neuropathic pain medication and healthy, non-irritated skin in the areas to be treated. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include the persistence of CIPN symptoms for at least one month post-chemotherapy with taxanes and/or platinum salts, and a sensory CIPN grade of 2 or higher according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE v.5.0). Participants must not have any planned neurotoxic chemotherapy in the six months following inclusion and must be affiliated with a social security scheme. The trial aims to compare the efficacy of a capsaicin 179 mg patch to daily duloxetine in improving painful CIPN over a five-week treatment period.

The clinical trial is designed to evaluate the efficacy of a **capsaicin** 179 mg patch compared to oral **duloxetine** in patients with chemotherapy-induced peripheral neuropathy (CIPN). This is a phase 3, randomized, open-label study with a multicentric approach. The trial aims to demonstrate that a single application of the capsaicin patch improves painful CIPN symptoms more effectively than daily administration of duloxetine over a 5-week treatment period. The study is expected to conclude by June 2027, with recruitment starting in October 2023.

Participants will be randomly assigned to either the capsaicin patch group or the duloxetine group. The trial will follow a structured sequence of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as the presence of painful CIPN symptoms, stable neuropathic pain medication, and healthy skin in the treatment area. Participants must be at least 18 years old and provide informed consent. The primary endpoint is the percentage of patients experiencing a 30% improvement in pain severity at 6 weeks compared to baseline.

Follow-up visits are scheduled at weeks 6, 12, 19, and 26 to assess safety, efficacy, quality of life, and functional interference using validated scales such as the Brief Pain Inventory-Short Form and the EORTC QLQ-CIPN20. The end-of-study visit will occur at week 26, marking the completion of the trial. The expected duration of participant involvement is approximately 26 weeks, with conditions for early termination including adverse events, withdrawal of consent, or protocol non-compliance.

The clinical trial involves the use of **Duloxetine**, an experimental medication administered in the form of a gastro-resistant capsule, hard. The active substance, **Duloxetine**, is of chemical origin. The medication is administered orally with a maximum daily dose of 30 mg for a treatment period of 1 week, and another regimen with a maximum daily dose of 120 mg for a treatment period of 6 weeks. The dosing schedule is designed to ensure participant compliance, with regular monitoring to assess adherence to the prescribed regimen.

In addition to **Duloxetine**, the trial also includes the use of **Capsaicin** in the form of a cutaneous patch. The active substance, **Capsaicin**, is also of chemical origin. The patch is applied cutaneously with a maximum total dose of 358 mg, intended for a treatment period of 2 weeks. The application of the patch is accompanied by an anaesthetic to mitigate any potential discomfort during administration. Participant compliance with the patch application is monitored to ensure adherence to the treatment protocol.

The trial aims to compare the efficacy of the **Capsaicin** patch against the oral administration of **Duloxetine** in patients with chemotherapy-induced peripheral neuropathy. The study is designed as a phase 3 randomized multicentric open-label study, with the primary objective of demonstrating the improvement in painful symptoms after a 5-week treatment period. The trial does not involve any paediatric formulations, and all substances used are chemically derived.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the percentage of patients with **chemotherapy-induced peripheral neuropathy** (CIPN) experiencing a 30% improvement in their average pain severity score at 6 weeks compared to baseline, with measurements taken on day 1 of week 6. Secondary endpoints include the assessment of safety according to the CTC-AE v5.0 at multiple timepoints: week 6, week 12, week 19, and week 26. Efficacy on non-painful sensory symptoms such as tingling and numbness will be evaluated by the rate of patients achieving at least a 30% improvement in their sensory scale scores from the quality of life questionnaire-chemotherapy-induced peripheral neuropathy (QLQ-CIPN20 and NPSI) at the same timepoints.

Quality of life will be measured using the QLQ C30 and the SF-12 quality of life scale at baseline and at weeks 6, 12, 19, and 26. Functional interference will be assessed using the Brief Pain Inventory-Short Form (BPI-SF) at these intervals. Global improvement of CIPN will be evaluated by the total score of the EORTC QLQ-CIPN20, and patient satisfaction will be assessed by the Patient Global Impression of Change (PGIC) at weeks 6, 12, 19, and 26. The trial will also assess the demonstration of improved efficacy and safety after repeated applications of capsaicin through paired comparisons of different scores between baseline and subsequent weeks. Additionally, the psychometric properties will be evaluated using the French-CIPN20 for structural validity and known-group comparisons at baseline and at the time of patch application in the experimental arm for reliability.