To Evaluate the Efficacy and Safety of HSK16149 Capsule in Chinese Patients With Postherpetic Neuralgia

Study Overview
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Brief Summary
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Investigate the Efficacy and Safety of HSK16149 capsules in Chinese Postherpetic Neuralgia Following 12 Weeks Treatment in Comparison to Placebo

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 12-Week, Phase 3 Study to Evaluate the Efficacy and Safety of HSK16149 Capsules in Chinese Patients With Postherpetic Neuralgia

Conditions
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Postherpetic Neuralgia

Intervention / Treatment
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* Drug: HSK16149 20mg BID
* Drug: HSK16149 40mg 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; Outpatient, Patients can not stay in the hospital overnight; Patients must have pain present for more than 1 months after the healing of the herpes zoster skin rash; At Screening, pain scale (VAS) of ≥40 mm; Exclusion Criteria: Peripheral neuropathy or pain unrelated to PHN that may confuse the assessment of PHN; 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:1)Neutrophils < 1.5 × 109/L, or platelet < 90 × 109/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 m2, or 4)Creatine kinase > 2.0 × ULN. Uncontrolled diabetes(HbA1c≥11.0% at screening) ; History of substance abuse or alcohol abuse; 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); Patients who have undergone neurolytic or neurosurgical therapy 1 week before screening for postherpetic neuralgia; Failure to response to previous treatment with pregabalin at doses ≥ 300 mg/d or gabapentin at doses ≥ 1200 mg/d for treatment of PHN; 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; Mechanical operators who are engaged in high-altitude operations, motor vehicle driving and other dangerous machinery operators; Participated in another clinical study within 30 days prior to screening; Other conditions unlikely to participate in this trial.

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>HSK16149 20mg, orally twice a day for 12 weeks | Drug: HSK16149 20mg BID<br>* HSK16149 20mg, orally twice a day, treatment period; 12-weeks fixed dose<br>|
| Experimental: HSK16149 40mg BID<br>HSK16149 40mg, orally twice a day for 12 weeks | Drug: HSK16149 40mg BID<br>* HSK16149 40mg, orally twice a day, treatment period; 12-weeks fixed dose<br>|
| Placebo Comparator: Placebo BID<br>placebo, orally twice a day for 12 weeks | Drug: Placebo BID<br>* Placebo, orally twice a day, treatment period; 12-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 ADPS between HSK16149 and placebo at week 12 | 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 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the response rate between HSK16149 and placebo at week 12 (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 12 | 
| Compare the change from baseline in ADPS between HSK16149 and placebo at week 1 to 12 | 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 12 | 
| Compare the change from baseline in Visual Analogue Scale（VAS） between HSK16149 and placebo at week 12 | 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 12 | 
| Compare the change from baseline in Short Form McGill Pain Questionnaire (SF-MPQ) between HSK16149 and placebo at week 12 | 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 12 | 
| Compare the change from baseline in Average Daily Sleep interference score（ADSIS） between HSK16149 and placebo at week 12 | he 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 12 | 
| Compare the total consumption of Acetaminophen and Paracetamol and Dihydrocodeine Tartrate between HSK16149 and placebo during the trial |  | From week 1 to week 12 | 
| Compare the change from baseline in EQ-5D-5L between HSK16149 and placebo at week 12 | The change from baseline in total EuroQol-5-Domain-5-Level health questionnaire | Baseline and week 12 | 
| AE（adverse event） to evaluate the safety of HSK16149 during the trial | Number and severity of AEs | From week 1 to week 12 | 
| Peak Plasma Concentration (Cmax) of HSK16149 capsules in Chinese patients with Postherpetic Neuralgia |  | Week 4,week 8,week 10,week 12 | 
| Area under the plasma concentration versus time curve (AUC) of HSK16149 capsules in Chinese patients with Postherpetic Neuralgia |  | Week 4,week 8,week 10,week 12 |