To Evaluate the Efficacy and Safety of HSK16149 Capsule in Chinese Patients With Diabetic Peripheral Neuropathic Pain

A Multicenter, Randomized, Double-Blind, Double-Dummy, Placebo- and Pregabalin Capsule-Controlled, 13-Week, Adaptive-design Phase 2/3 Study to Evaluate the Efficacy and Safety of HSK16149 Capsules in Chinese Patients With Diabetic Peripheral Neuropathic Pain

Investigate the efficacy and safety of HSK16149 capsules in Chinese diabetic peripheral neuropathic pain (DPNP) following 13 weeks treatment in comparison to placebo.

Inclusion Criteria:

1. Signed informed consent;
2. Males or females aged 18-75 years of age inclusive;
3. Diagnosis of diabetic peripheral neuropathic pain (DPNP) and diabetic peripheral neuropathy (DPN) pain ≥ 6 months;
4. HbA1c ≤ 9.0% at screening and on a stable antidiabetic medication regimen for at least 30 days prior to screening;
5. At Screening, pain scale (VAS) of ≥40 mm and <90 mm.

Exclusion Criteria:

1. Peripheral neuropathy or pain unrelated to DPN that may confuse the assessment of DPNP.

2. Skin conditions in the area affected by neurupathy that could alter sensation.

3. Chronic systemic diseases that may affect subjects' participation in the study.

4. Severe hematologic, hepatic or renal dysfunction, the subject will be excluded if:

   1. Neutrophils < 1.5 × 10^9/L, or platelet < 90 × 10^9/L, or hemoglobin < 100 g/L, or
   2. AST/ALT > 2.5 × upper limit of normal (ULN), or TBIL > 1.5 × ULN, or
   3. Estimation of glomerular filtration rate (eGFR) < 60 mL/min / 1.73 m^2, or
   4. Creatine kinase > 2.0 × ULN.

5. History of substance abuse or alcohol abuse.

6. Acute complications of diabetes in the 6 months prior to screening.

7. Any active infections at screening.

8. HBsAg or HCV Ab positive, or HIV Ab positive, or serum TP Ab positive.

9. Inability or unwillingness to discontinue any other prohibited concomitant medications (see Section 6.3).

10. Failure to response to previous treatment with pregabalin at doses ≥ 300 mg/d or gabapentin at doses ≥ 1200 mg/d for treatment of DPNP.

11. History of allergic or medically significant adverse reaction to investigational products or their excipients, acetaminophen or related compounds.

12. History of suicidal behavior or attempted suicide.

13. Pregnant or preparing for pregnancy or breastfeeding during the study period, or subjects were not willing to use reliable contraceptives methods from the date of ICF signature until 28 days after the last trial drug administration, or planning to use progesterone contraceptives during this period.

14. Participated in another clinical study within 30 days prior to screening.

15. Other conditions of the subjects who are unlikely to comply with the protocol.

16. Could potentially affect a subject's safety.