Crisugabalin for Radiotherapy-Related Neuropathic Pain

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 5months.

3. Histologically confirmed head and neck tumors treated with radiotherapy at least 6months prior to screening.

4. Average NRS pain score ≥4 over 7 days during the screening period, with painlocalized to nerve-innervated areas corresponding to the radiotherapy site, such asthe head, face, neck, and arms.

5. Diagnosis of neuropathic pain persisting for at least 4 weeks, confirmed by twotrained neurologists based on clinical history, symptoms, signs, and a LeedsAssessment of Neuropathic Symptoms and Signs (LANSS) score ≥12 (Chinese version).

6. Adequate cognitive and language abilities to communicate and complete studyquestionnaires.

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, orhemoglobin <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 m²or undergoing dialysis.

• Creatine kinase >2× ULN.

2. Chronic systemic diseases that may interfere with study participation, including butnot 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), orrecurrent asthma.

• Chronic gastrointestinal diseases, such as liver fibrosis, recurrentindigestion or diarrhea, or peptic ulcers.

• Neurological or psychiatric conditions affecting pain assessment, includingepilepsy, recurrent dizziness, headache, memory, or cognitive disorders;cerebrovascular accidents or transient ischemic attacks within 6 months ofscreening.

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

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

5. Neuropathic pain not caused by radiotherapy, such as postherpetic neuralgia,diabetic neuropathy, HIV-related neuropathy, spinal cord injury, or otherneurological 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 daysafter 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 beforescreening, with prohibition maintained throughout the study.

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