A Randomized, Open-Label, Non-Inferiority Trial Comparing Lacosamide and Duloxetine for Chemotherapy-Induced Neuropathic Pain

The primary objective of this study is to explore the **analgesic effect** of lacosamide compared to duloxetine in patients with painful chemotherapy-induced polyneuropathy. This is clinically relevant as it aims to determine the efficacy of these two medications in managing neuropathic pain resulting from chemotherapy, which is a significant concern for patients undergoing cancer treatment.

Secondary objectives include:

• To assess the side effect profile of lacosamide and duloxetine, which is crucial for understanding the safety and tolerability of these treatments.
• To phenotype patients with painful chemotherapy-induced polyneuropathy using quantitative sensory testing, conditioned pain modulation, offset analgesia, and cornea confocal microscopy. This objective aims to better understand the characteristics of the neuropathy in affected patients.
• To correlate the chemotherapy-induced polyneuropathy phenotype of patients with the treatment effect of lacosamide and duloxetine, which may provide insights into personalized treatment approaches based on patient-specific neuropathic profiles.

The clinical trial focuses on individuals experiencing **chemotherapy-induced neuropathic pain**. The study population includes both male and female participants, aged 18 years and older, who have undergone chemotherapy with agents such as taxanes, platinums, vicalkiniods, or bortezomib. Participants must exhibit symptoms of neuropathic pain persisting for at least three months post-chemotherapy, with a pain score of 4 or higher. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include the ability to provide informed consent and indications of small- or large-fiber neuropathy as determined by quantitative sensory testing. Lifestyle factors such as diet and physical activity are not specified as part of the selection process.

The clinical trial is designed as a **randomized**, open-label, non-inferiority study to evaluate the efficacy of **lacosamide** compared to **duloxetine** in patients experiencing **chemotherapy-induced neuropathic pain**. The primary objective is to assess the analgesic effect of lacosamide relative to duloxetine in this patient population. The trial will span an estimated duration from January 11, 2021, to December 31, 2025, with a maximum treatment period of 8 weeks for each participant. Participants will be randomly assigned to receive either Cymbalta 30 mg hard gastro-resistant capsules or Vimpat 50 mg film-coated tablets, both administered orally.

The study will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be confirmed based on criteria such as age over 18 years, ability to provide informed consent, and a pain score of 4 or higher. Participants must have undergone chemotherapy with specific agents and exhibit symptoms of neuropathic pain at least 3 months post-chemotherapy. Follow-up visits will monitor pain intensity, patient satisfaction, and side effect profiles, with the primary endpoint being the pain intensity score during the last 4 weeks of treatment.

Participants are expected to be involved in the study for a total of 8 weeks, with conditions for early termination including withdrawal of consent or adverse events that compromise safety. The trial aims to provide valuable insights into the comparative effectiveness of these treatments, contributing to improved management strategies for patients with chemotherapy-induced neuropathic pain.

The clinical trial involves the administration of **Cymbalta** (duloxetine) as an experimental medication. Cymbalta is provided in the form of hard gastro-resistant capsules, each containing 30 mg of the active substance **duloxetine**. The medication is administered orally, with a maximum daily dose of 120 mg, divided into two doses per day. The treatment period for Cymbalta is set for a maximum of 8 weeks. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, the trial includes a comparator treatment using **Vimpat** (lacosamide). Vimpat is supplied as film-coated tablets, each containing 50 mg of the active substance **lacosamide**. Similar to Cymbalta, Vimpat is administered orally, with a maximum daily dose of 600 mg, also divided into two doses per day. The treatment duration for Vimpat is also limited to 8 weeks. Compliance with the dosing schedule for Vimpat will be closely monitored to maintain the integrity of the trial data.

Both medications, Cymbalta and Vimpat, are chemically derived and have been authorized for use in the trial. The trial aims to evaluate the analgesic effect of lacosamide compared to duloxetine in patients suffering from painful chemotherapy-induced polyneuropathy. No additional non-experimental treatments, such as placebo or standard-of-care therapy, are included in this study. The trial is designed to ensure rigorous monitoring of participant adherence to the treatment protocols to accurately assess the efficacy of the medications under investigation.

The efficacy of the clinical trial will be assessed by evaluating the analgesic effect of **lacosamide** compared to **duloxetine** in patients with painful chemotherapy-induced polyneuropathy. The primary endpoint for efficacy assessment is the pain intensity score during the last four weeks of treatment. This will be measured using a validated pain scale to ensure accurate and reliable data collection. Secondary endpoints include patient satisfaction with the treatment and the side effect profile, which will provide additional insights into the overall effectiveness and tolerability of the treatments. Data collection will occur at specified intervals throughout the trial, with a focus on the final four weeks to capture the primary endpoint. The analysis will involve comparing the changes in pain intensity scores and secondary outcomes between the two treatment groups to determine non-inferiority of lacosamide relative to duloxetine.