Prospective, placebo-controlled clinical trial with Aconite Pain Oil in oncological patients undergoing chemotherapy to prevent chemotherapy-induced polyneuropathy (CIPN) grade II, to reduce symptoms typical of CIPN and to improve the quality of life of patients with CIPN

The primary objective of this clinical trial is to evaluate the efficacy of **Aconite Pain Oil** in reducing the risk of **chemotherapy-induced polyneuropathy (CIPN)** of grade II and higher by 35% during the treatment period, as compared to a placebo. This is clinically relevant as CIPN is a common and debilitating side effect of chemotherapy, impacting patients' quality of life and potentially limiting the effectiveness of cancer treatment.

Secondary objectives include:

• Reduction of CIPN symptoms during treatment with verum compared to placebo.
• Improvement in quality of life and sleep for patients during treatment with verum compared to placebo.
• Reduction in anxiety and depression during treatment with verum compared to placebo.
• Assessment of patient satisfaction.
• Evaluation of safety and tolerability during treatment.
• Analysis of events related to chemotherapy due to CIPN during treatment with verum compared to placebo.
• Examination of medication use regarding CIPN during treatment with verum compared to placebo.
• Reduction in the development of grade-III CIPN during treatment with verum compared to placebo.
• Regression of CIPN that occurred during chemotherapy after discontinuation of chemotherapy by continued use of verum compared to placebo.
• Prevention of CIPN occurrence after discontinuation of chemotherapy by continued use of verum compared to placebo.

The clinical trial involves participants diagnosed with **chemotherapy-induced polyneuropathy (CIPN)**. The study population includes both male and female subjects, with an age range starting from 18 years. Participants are required to have a **Karnofsky Index** of 70% or higher, indicating a relatively stable general health status. The trial does not include a vulnerable population. Participants are individuals with solid tumors who are scheduled to receive unmodified chemotherapy with taxanes or platinum derivatives, or their combination, for a minimum duration of three months. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants. Key inclusion criteria include a signed consent form, a minimum life expectancy of 12 months, and for those of childbearing age, a negative pregnancy test is required. The selection process for the trial population is not detailed in the provided data.

The clinical trial is designed as a **randomized**, **double-blind**, placebo-controlled study aimed at evaluating the efficacy of Aconit Schmerzöl in preventing and reducing symptoms of **chemotherapy-induced polyneuropathy (CIPN)** in patients undergoing chemotherapy. The trial will involve participants with solid tumors who are scheduled to receive unmodified chemotherapy with **taxanes** or **platinum compounds** for a minimum of three months. The primary objective is to reduce the risk of CIPN of grade II and higher by 35% using the active treatment compared to placebo. The trial will employ a COX regression model to analyze the primary endpoint, which is the time to CIPN of grade II or higher.

The trial is expected to commence recruitment on January 1, 2024, and conclude by August 31, 2027. Participants will be involved in the study for a maximum treatment period of six to seven months, depending on the specific treatment regimen. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, Karnofsky Index, and life expectancy, followed by regular follow-up visits to monitor the occurrence and progression of CIPN symptoms. The end-of-study visit will assess the overall impact of the treatment on CIPN symptoms and quality of life.

Participants may be withdrawn from the study if they experience adverse events that compromise their safety, if they withdraw consent, or if they fail to comply with the study protocol. The trial will also assess secondary endpoints, including the time to occurrence of CIPN grade III, regression of CIPN symptoms, and various measures of sensory and motor function over time. The study will utilize descriptive and exploratory statistical methods to evaluate these secondary outcomes. The trial is categorized as a therapeutic confirmatory study and is not considered low intervention.

The clinical trial involves the administration of **Taxanes**, a class of **cytostatica** used in the treatment of cancer. Taxanes are administered via **infusion** with a maximum daily dose of 175 mg/m² and a total maximum dose of 1400 mg/m² over a treatment period of up to 6 weeks. The pharmaceutical form is not specified, and the administration is monitored to ensure compliance with the dosing schedule.

**Aconit Schmerzöl** is utilized as an auxiliary treatment in the trial. It is a **cutaneous liquid** containing active substances such as **D-Camphor**, **Lavender Oil**, **Quarz Dil. D9 Oleos.**, and **Aconitum Napellus E Tubere Ferm 33C Dil. D9 Oleos.**. The product is applied externally with a maximum daily dose of 12 ml and a total maximum dose of 2520 ml over a 7-week period. A dosing cup is provided to measure the specific volume of oil for accurate administration.

**Carboplatin**, another **cytostatica**, is administered via **infusion** with a maximum daily dose of 400 mg/m² and a total maximum dose of 3200 mg/m² over a treatment period of up to 6 weeks. The pharmaceutical form is identified as PHF00230MIG, and the administration is carefully monitored to ensure adherence to the prescribed dosing regimen.

**Refined Peanut Oil** is used as a placebo in the trial. It is applied topically with a maximum daily dose of 12 ml and a total maximum dose of 2520 ml over a 7-week period. The oil serves as a control to evaluate the efficacy of the experimental treatments in preventing chemotherapy-induced polyneuropathy (CIPN) and improving the quality of life in oncological patients undergoing chemotherapy.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is defined as the time to the occurrence of **chemotherapy-induced polyneuropathy (CIPN)** of grade II or higher. The analysis will employ a COX regression model, incorporating stratification variables of randomization as covariates. The hypothesis tested will be H0: HR ≥ 1 versus H1: HR < 1.

Secondary endpoints include various measures such as the time to occurrence of CIPN grade III, regression of CIPN after chemotherapy discontinuation, and the absence of CIPN post-chemotherapy with continued use of the investigational product. These will be descriptively presented and subjected to exploratory statistical testing. Additional assessments will cover thermoception, tactile perception, nociception, pallaesthesia, fine motor skills, hand strength, and various reflexes over time, utilizing mixed logistic and linear regression models for analysis. Patient-reported outcomes will be evaluated using instruments like the EORTC-QLQ-CIPN20, EORTC-QLQ-C30, and the Insomnia Severity Index, among others. These will be descriptively presented and analyzed using mixed linear regression models. Patient satisfaction and events related to chemotherapy due to CIPN will also be documented and analyzed descriptively.