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

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

Official Title
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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

Conditions
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Diabetic Peripheral Neuropathic Pain

Intervention / Treatment
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* Drug: HSK16149 20mg BID
* Drug: HSK16149 40mg BID
* Drug: HSK16149 60mg BID
* Drug: HSK16149 80mg BID
* Drug: Pregabalin 150mg BID
* Drug: Placebo BID


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Males or females aged 18-75 years of age inclusive; Diagnosis of diabetic peripheral neuropathic pain (DPNP) and diabetic peripheral neuropathy (DPN) pain ≥ 6 months; HbA1c ≤ 9.0% at screening and on a stable antidiabetic medication regimen for at least 30 days prior to screening; At Screening, pain scale (VAS) of ≥40 mm and <90 mm. Exclusion Criteria: Peripheral neuropathy or pain unrelated to DPN that may confuse the assessment of DPNP. Skin conditions in the area affected by neurupathy that could alter sensation. Chronic systemic diseases that may affect subjects' participation in the study. Severe hematologic, hepatic or renal dysfunction, the subject will be excluded if: Neutrophils < 1.5 × 10^9/L, or platelet < 90 × 10^9/L, or hemoglobin < 100 g/L, or AST/ALT > 2.5 × upper limit of normal (ULN), or TBIL > 1.5 × ULN, or Estimation of glomerular filtration rate (eGFR) < 60 mL/min / 1.73 m^2, or Creatine kinase > 2.0 × ULN. History of substance abuse or alcohol abuse. Acute complications of diabetes in the 6 months prior to screening. Any active infections at screening. HBsAg or HCV Ab positive, or HIV Ab positive, or serum TP Ab positive. Inability or unwillingness to discontinue any other prohibited concomitant medications (see Section 6.3). Failure to response to previous treatment with pregabalin at doses ≥ 300 mg/d or gabapentin at doses ≥ 1200 mg/d for treatment of DPNP. History of allergic or medically significant adverse reaction to investigational products or their excipients, acetaminophen or related compounds. History of suicidal behavior or attempted suicide. 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. Participated in another clinical study within 30 days prior to screening. Other conditions of the subjects who are unlikely to comply with the protocol. Could potentially affect a subject's safety.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK16149 20mg BID<br> | Drug: HSK16149 20mg BID<br>* HSK16149 20mg, orally twice a day, treatment period; 13-weeks fixed dose.<br>|
| Experimental: HSK16149 40mg BID<br> | Drug: HSK16149 40mg BID<br>* HSK16149 40mg, orally twice a day, treatment period; 13-weeks fixed dose.<br>|
| Experimental: HSK16149 60mg BID<br> | Drug: HSK16149 60mg BID<br>* HSK16149 60mg, orally twice a day, treatment period; 1-week titration and 12-weeks fixed dose.<br>|
| Experimental: HSK16149 80mg BID<br> | Drug: HSK16149 80mg BID<br>* HSK16149 80mg, orally twice a day, treatment period; 1-week titration and 12-weeks fixed dose.<br>|
| Active Comparator: Pregabalin 150mg BID<br> | Drug: Pregabalin 150mg BID<br>* Pregabalin 150mg, orally twice a day, treatment period; 1-week titration and 12-weeks fixed dose.<br>|
| Placebo Comparator: Placebo BID<br> | Drug: Placebo BID<br>* Placebo, orally twice a day, treatment period; 13-weeks fixed dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the change from baseline in Average Daily Pain Score（ADPS） between HSK16149 and placebo at week 5. | The mean change in average daily pain score (ADPS) was measured using a 11-point numeric rating scale (NRS; 0 [no pain] to 10 [worst possible pain]. The rating averaged over a 7-day period and was based on entries in patients' daily pain diaries. | Baseline and week 5 | 
| Compare the change from baseline in Average Daily Pain Score （ADPS） between HSK16149 and placebo at week 13. | The mean change in average daily pain score (ADPS) was measured using a 11-point numeric rating scale (NRS; 0 [no pain] to 10 [worst possible pain]. The rating averaged over a 7-day period and was based on entries in patients' daily pain diaries. | Baseline and week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the response rate between HSK16149 and placebo at week 5 (Proportion of subjects whose ADPS decreased by ≥30% and ≥50% from baseline ). | Ratio of Participants Responding to Treatment, as Measured by Average Daily Pain Score (ADPS) Reduction from Baseline. The ADPS is used to determine categorical response rates. | Baseline and week 5 | 
| AE, laboratory tests, physical and neurological examination, vital signs and 12-lead ECG to evaluate the safety of HSK16149 in 5 weeks post treatment. | Number and severity of AEs, clinical laboratory abnormalities, physical examinations, 12-lead electrocardiograms (ECGs), and vital signs. | From week 1 to week 5 | 
| Compare the response rate between HSK16149 and placebo at week 13 (Proportion of subjects whose ADPS decreased by ≥30% and ≥50% from baseline ). | Ratio of Participants Responding to Treatment, as Measured by Average Daily Pain Score (ADPS) Reduction from Baseline. The ADPS is used to determine categorical response rates. | Baseline and week 13 | 
| Compare the change from baseline in ADPS between HSK16149 and placebo at week 1 to 13. | The mean change in average daily pain score (ADPS) was measured using a 11-point numeric rating scale (NRS; 0 [no pain] to 10 [worst possible pain]. The rating averaged over a 7-day period and was based on entries in patients' daily pain diaries. | From week 1 to week 13 | 
| Compare the change from baseline in Visual Analog Scale （VAS） between HSK16149 and placebo at week 13. | VAS, in which the participant rates pain on a 100 mm-long horizontal line, where 0 mm = no pain and 100 mm = worst possible pain. | Baseline and week 13 | 
| Compare the change from baseline in Short-Form McGill Pain Questionnaire (SF-MPQ) between HSK16149 and placebo at week 13. | Participants rate their pain in three parts of the questionnaire, which are combined into a single pain intensity score: Part 1 - fifteen descriptors of pain intensity, on a scale of 0 (none) to 3 (severe) Part 2 - a visual analog scale (VAS), in which the participant rates pain on a 100 mm-long horizontal line, where 0 mm = no pain and 100 mm = worst possible pain Part 3 - a Present Pain Intensity index in which the participant rates present pain intensity on a scale of 0 (no pain) to 5 (most intense pain) | Baseline and week 13 | 
| Compare the Patient Global Impression of Change（PGIC） between HSK16149 and placebo at week 13. | Patient global impression of change (PGIC) on a 7-point categorical scale, where 1 = very much improved and 7 = very much worse. | Week 13 | 
| Compare the change from baseline in Average Daily Sleep Interference score (ADSIS) between HSK16149 and placebo at week 13. | The sleep interference scores on a scale of 0-10, where 0 = pain did not interfere with sleep to 10 = pain completely interfered with sleep. The weekly ADSIS is based on participants daily sleep interference scores. | Baseline and week 13 | 
| Compare the change from baseline in EuroQol-5-Domain-5-Level health questionnaire (EQ-5D-5L) between HSK16149 and placebo at week 13. | The change from baseline in total EuroQol-5-Domain-5-Level health questionnaire. | Baseline and week 13 | 
| AE, laboratory tests, physical and neurological examination, vital signs and 12-lead ECG to evaluate the safety of HSK16149 during the trial. | Number and severity of AEs, clinical laboratory abnormalities, physical examinations, 12-lead electrocardiograms (ECGs), and vital signs. | From week 1 to week 14 | 
| Pharmacokinetic (PK) characteristics of HSK16149 capsules in Chinese patients with diabetic peripheral neuropathic pain. | Pharmacokinetics will be determined by measuring serum concentration of HSK16149. | Week 1,week 5,week 11,week 13 |