Crisugabalin for Radiotherapy-Related Neuropathic Pain

Crisugabalin Versus Pregabalin for Radiotherapy-Related Neuropathic Pain in Head and Neck Cancers: A Multicenter, Randomized, Open-Label, Non-Inferiority Trial

The purpose of this study is to evaluate whether Crisugabalin has similar efficacy compared to Pregabalin in reducing radiotherapy-related neuropathic pain (RRNP) in patients with head and neck cancers.

The primary objective of this study is to determine whether Crisugabalin provides non-inferior pain relief compared to Pregabalin in patients with head and neck cancer experiencing radiotherapy-related neuropathic pain. The trial adopts a multicenter, randomized, open-label design, and the primary endpoint is the change in Numeric Rating Scale (NRS) pain scores from baseline to 4 weeks. The study aims to provide new evidence to support treatment strategies for this condition, which significantly affects patients' quality of life.

Inclusion Criteria:

1. Ability to understand and voluntarily sign a written informed consent form.
2. Male or female patients aged ≥18 years with an expected survival of at least 5 months.
3. Histologically confirmed head and neck tumors treated with radiotherapy at least 6 months prior to screening.
4. Average NRS pain score ≥4 over 7 days during the screening period, with pain localized to nerve-innervated areas corresponding to the radiotherapy site, such as the head, face, neck, and arms.
5. Diagnosis of neuropathic pain persisting for at least 4 weeks, confirmed by two trained neurologists based on clinical history, symptoms, signs, and a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score ≥12 (Chinese version).
6. Adequate cognitive and language abilities to communicate and complete study questionnaires.

Exclusion Criteria:

1. Severe abnormalities in hematological, hepatic, or renal function, as evidenced by:

   • Hematology: Neutrophil count <1.5×10⁹/L, platelet count <90×10⁹/L, or hemoglobin <100 g/L.
   • Liver function: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper limit of normal (ULN), or total bilirubin (TBIL) >1.5× ULN.
   • Renal function: Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or undergoing dialysis.
   • Creatine kinase >2× ULN.

2. Chronic systemic diseases that may interfere with study participation, including but not limited to:

   • Severe cardiopulmonary diseases such as unstable angina, myocardial infarction, severe arrhythmia, WHO functional classification III-IV heart failure, uncontrolled hypertension (systolic BP >160 mmHg or diastolic BP >100 mmHg), or recurrent asthma.
   • Chronic gastrointestinal diseases, such as liver fibrosis, recurrent indigestion or diarrhea, or peptic ulcers.
   • Neurological or psychiatric conditions affecting pain assessment, including epilepsy, recurrent dizziness, headache, memory, or cognitive disorders; cerebrovascular accidents or transient ischemic attacks within 6 months of screening.

3. Known allergy to study drugs or chemically related compounds.

4. Current diagnosis of tumor recurrence or metastasis associated with tumor-related pain.

5. Neuropathic pain not caused by radiotherapy, such as postherpetic neuralgia, diabetic neuropathy, HIV-related neuropathy, spinal cord injury, or other neurological diseases.

6. Use of pregabalin/crisugabalin within 4 weeks before screening.

7. Pregnant, planning to become pregnant during the study, or breastfeeding. Participants and their partners unwilling to use reliable contraception (e.g., condoms, spermicides, intrauterine devices) from the time of consent until 28 days after the last dose of study medication.

8. Participation in any other clinical trial within 30 days prior to screening.

9. Any other condition deemed unsuitable for study participation by the investigator.

10. Use of prohibited medications within at least 5 half-lives of the drug before screening, with prohibition maintained throughout the study.

11. Previous use of pregabalin ≥300 mg/day or gabapentin ≥1200 mg/day deemed ineffective.