A Study to Evaluate the Efficacy and Safety of HR18042 Tablets in the Treatment of Postoperative Pain of Impacted Tooth.

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the Efficacy and safety of HR18042 tablets for the Treatment of Post-surgical Pain After extraction of impacted tooth, find the optimal dose.

Official Title
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A Multicenter,Randomized, Double-blind, Dose Ranging , Active- and Placebo-controlled, Parallel Groups, Phase II Clinical Trial to Evaluate the Efficacy and Safety of HR18042 Tablets for the Treatment of Postoperative Pain of Impacted Tooth.

Conditions
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Moderate to Severe Acute Pain

Intervention / Treatment
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* Drug: HR18042
* Drug: HR18042
* Drug: HR18042
* Drug: Tramadol hydrochloride ER
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 75 years old. Subjects must have a plan of extraction of impacted tooth. Subjects with moderate to severe pain (VAS score ≥ 50mm).This must be measured within a maximum of 4 hours after the end of extraction of impacted tooth. weight at least 45kg,and no more than 100kg. If a female is of child-bearing potential, she must be using highly effective methods of contraception throughout the study. Willingness to comply with the study procedures and requirements. willing and able to provide written informed consent for this study. Exclusion Criteria: any analgesic medication other than preoperative or intraoperative anaesthetic agents within 12h before taking trial medication medication a longacting NSAID within 4 days,or a shortacting NSAID within 1 days prior to dosing. any anti-depressive medication, selective serotonin reuptake inhibitors (SSRIs), diet pills et.al. with 30 days of study entry. Oral surgical site combined with infection. Severe cardiovascular and cerebrovascular diseases. Severe gastrointestinal disease. had a history of seizures or drug or alcohol abuse. uncontrolled hypertension. significant abnormal electrocardiogram significant abnormal laboratory value. Allergic to the study drug and ingredients. Pregnancy, lactation or recent Pregnant plan; Subjects who participated in a clinical research study involving an experimental drug before 30 days of study entry. other conditions unsuitable for participation in the study.

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
Interventional Model Description: A Multicenter,randomized, double-blind, Dose Ranging , controlled with active treatment and placebo, parallel groups, Phase II clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HR18042 100mg<br> | Drug: HR18042<br>* Tablet, Dosing frequency: once daily, Route of administration: oral<br>|
| Experimental: HR18042 125mg<br> | Drug: HR18042<br>* Tablet,Dosing frequency: once daily, Route of administration: oral<br>|
| Experimental: HR18042 200mg<br> | Drug: HR18042<br>* Tablet,Dosing frequency: once daily, Route of administration: oral<br>|
| Active Comparator: Tramadol hydrochloride ER 100mg<br> | Drug: Tramadol hydrochloride ER<br>* Tablet,Dosing frequency: once daily, Route of administration: oral<br>|
| Placebo Comparator: Placebo to match HR18042 and Tramadol hydrochloride ER<br> | Drug: Placebo<br>* Tablet,Dosing frequency: once daily, Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Sum of Pain Intensity Differences（SPID） | SPID is derived as the weighted Sum of Pain Intensity Differences (baseline pain - current pain), measured at different time points via the PI-VAS. Time between two consecutive measurements will be used for weighting. Larger values indicate larger pain relief. | 0-8hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Sum of Pain Intensity Differences（SPID） |  | 0-4hours | 
| the Sum of Pain Intensity Differences（SPID） |  | 0-12hours | 
| Pain Intensity Differences（PID） | Include pain intensity differences(PIDs) from baseline at each time point. measured at different time points via the PI-VAS. | 0-12hours | 
| Pain relief（PAR） | pain relief (PAR) on a 5-point Likert scale (0, none, 1, a little, 2, some,3, a lot, 4, complete). | 0-12hours | 
| the Sum of Pain relief Differences（SPAR） | SPAR is derived as the weighted Sum of Pain relief, measured at different time points via the 5-point Likert scale. Time between two consecutive measurements will be used for weighting. Larger values indicate larger pain relief. | 0-4hours | 
| the Sum of Pain relief Differences（SPAR） |  | 0-8hours | 
| the Sum of Pain relief Differences（SPAR）. |  | 0-12hours | 
| Subject who reaches a 30% reduction in pain intensity from baseline |  | 4hours、8hours、12hours | 
| Subject who reaches a 50% reduction in pain intensity from baseline |  | 4hours、8hours、12hours | 
| time to perceptible pain relief |  | 0-12hours | 
| time to meaningful pain relief | Patients used one stopwatch to record the time to 'perceptible' PAR and another stopwatch for the time to'meaningful' PAR.Patients started timing upon intake of study medication and stopped one stopwatch at the onset of perceptible PAR and another upon achieving meaningful PAR. | 0-12hours | 
| Time to first use of rescue medication |  | 0-12hours | 
| Proportion of subjects who take of at least 1 dose of rescue medication |  | 0-12hours | 
| Subject's overall assessment of study medication | Patients made an overall assessment of the study medication using a verbal rating scale (excellent, verygood, good, fair, poor). | 12hours |