Phase III Efficacy and Tolerability Trial of the Fixed Dose Combination of Etodolac 400 mg and Cyclobenzaprine 10 mg Versus Isolated Active Substances in Pain Control After Impacted Third Molar Extraction

Study Overview
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Brief Summary
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This Phase III study will compare the efficacy and tolerability of a Fixed Dose Combination of Etodolac + Cyclobenzaprine versus the isolated drugs in postoperative pain control after impacted third molar extraction.

Official Title
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Phase III Randomized, Unicentric, Double-masked, Parallel Trial for the Efficacy and Tolerability of the Fixed Dose Combination of Etodolac 400 mg and Cyclobenzaprine 10 mg Versus the Isolated Active Substances (Flancox® 400 mg And Miosan® 10 mg) in Postoperative Pain Control After Impacted Third Molar Extraction

Conditions
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Pain, Acute

Intervention / Treatment
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* Drug: Fixed Dose Combination
* Drug: Etodolac
* Drug: Cyclobenzaprine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy research participants of both sexes (male and female non-pregnant), aged 18 years or over, underwent impacted third molar extraction surgery Exclusion Criteria: Presence of any event and / or pathology at the site of interest that may interfere with and contraindicate the performance of the surgical procedure at the discretion of the Investigator, including periodontitis, odontogenic tumors or cysts (associated or not with the third molar), trauma, presence of Inflammation and / or infection; Present or past history of any cardiac, gastrointestinal, respiratory, hepatic, renal, endocrine, neurological, metabolic, psychiatric, hematological event; Previous diagnosis of alcohol and drug abuse defined by DSM-V; Current or past history (for less than 12 months) of smoking; Use of illicit drugs; History of bleeding / bleeding or coagulation disorders, gastric ulcer and / or active peptic hemorrhage; Any finding of clinical (clinical / physical), laboratory or cardiac evaluation (ECG) observation that is interpreted by the investigating physician as a risk to the participant; Use of drugs that potentially interfere with the kinetics / dynamics of acetaminophen or any other medicinal product considered clinically significant by the Investigator; Known hypersensitivity to the active principles used during the study (etodolac and cyclobenzaprine); Women in gestation or breastfeeding, as well as women who present a positive pregnancy test (β - hCG) during the study screening / selection period; Professionals directly involved in the realization of the present study and their relatives; Participant of the research that has participated in clinical study protocols in the last 12 (twelve) months, unless the Investigator deems that there may be direct benefit to it.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>1 active treatment (Fixed Dose Combination) + 2 placebos | Drug: Fixed Dose Combination<br>* Fixed Dose Combination of Etodolac 400 mg + Cyclobenzaprine 10 mg<br>|
| Active Comparator: Group 2<br>1 active treatment (Cyclobenzaprine) + 2 placebos | Drug: Cyclobenzaprine<br>* Individual drug<br>* Other names: Miosan;|
| Active Comparator: Group 3<br>1 active treatment (Etodolac) + 2 placebos | Drug: Etodolac<br>* Individual drug<br>* Other names: Flancox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Superiority of the Fixed Dose Combination versus Isolated active substances | The Primary outcome will be accessed by the individual response rate in relation to the pain intensity calculated by the Visual Analogic Scale (VAS) scale performed after 4 hours of administration of the first dose of medicines | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual response rate | Individual response rate in relation to the evaluation of pain intensity calculated through the Visual Analogic Scale (VAS) measure in times 6h, 12h, 24h, 48h and 72h | 6h, 12h, 24h, 48h and 72h | 
| Edema | Absence of edema after 4 hours of drug administration and at the end of treatment | 4 hours | 
| Mandibula constriction | Absence of mandibular constriction after 4 hours of drug administration and at the end of treatment | 4 hours | 
| Use of rescue medication | Proportion of participants requiring the use of rescue medication over the 3 days of treatment in each treatment group | 3 days |