Comparative Study of Loxoprofen Sodium Transdermal Patch and Loxonin® Tablets for the Treatment of Acute Trauma

Study Overview
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Brief Summary
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This study evaluates the non-inferiority of the new transdermal patch dosage form containing loxoprofen sodium (100 mg - Daiichi-Sankyo) in comparison with oral Loxonin® (60 mg tablet - Daiichi-Sankyo) for the treatment of acute traumatic injuries.

Detailed Description
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The primary objective of the study will be to verify the efficacy of loxoprofen in its new dosage form for the treatment of pain. Primary endpoint: score of change in spontaneous pain by using the visual analogue scale (VAS) after seven days of treatment. Secondary endpoints: intensity of pain evaluated by the VAS scale on each study visit, impression of the research subject checked by a 7-point scale, changes in clinical symptoms, and frequency of use of the rescue medication. Evaluation of drug safety as per the occurrence of adverse events and serious adverse events. This is a double blind, randomized, comparative study, with a total of 208 subjects divided into 2 groups: 104 subjects treated with loxoprofen sodium (transdermal patch 100 mg; Daiichi-Sankyo) associated with placebo tablet (experimental group) and 104 subjects treated with transdermal patch of placebo associated with Loxonin® (loxoprofen sodium 60 mg - Daiichi-Sankyo - control group). In order to be enrolled in the study, the research subject shall sign and date the informed consent form and shall have between 18 and 65 years old, with recent (48 hours before study baseline visit) posttraumatic disease (contusion or sprain) of lower or upper limbs (except for fingers and toes), with at least one moderate or more serious symptom of pain or inflammation according to the investigator's evaluation, with no prior (5 days before initiating the study treatment) or current use of pain medication, NSAIDs, anti-inflammatory drugs, or steroids. In addition, research subjects shall not experience cardiovascular, renal, or hematological diseases, diabetes mellitus, psychiatric disorders, or any other serious comorbidity (at the investigator's discretion), apparent complication of a bacterial infection, fracture or requiring immobilization with cast or surgical procedure, neck sprain, too small area affected (e.g.,fingers) not allowing the use of the transdermal patch, skin sores in application site, bad or sensitive condition of the skin with prior history of dermatitis due to the use of topic drugs, prior history of gastrointestinal bleeding or ulcers, bronchial asthma of any cause, allergy to loxoprofen or any other NSAIDs. Also, the subjects should not have participated in any other clinical study in the last 12 months and pregnant or breastfeeding subjects or those who want to become pregnant or who refuse to use a safe birth control method during the study will not be enrolled in the study. The accrual period anticipated for the study will be of 4 to 5 months as of the regulatory approval of the protocol. Total duration of participation of each research subject and active treatment will be of 1 week.

Official Title
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A Phase III, Randomized, Double Blind, Non-inferiority, Comparative Study of the New Transdermal Patch Dosage Form Containing Loxoprofen Sodium (100 mg) and Loxonin® (60 mg Tablet) for the Treatment of Acute Traumatic Injuries

Conditions
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Trauma, Pain

Intervention / Treatment
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* Drug: Transdermal Patch
* Drug: Loxoprofen sodium
* Drug: Placebo (for loxoprofen sodium)
* Drug: Placebo (for transdermal patch)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For enrollment in this study, the eligible research subjects shall meet all criteria below: Sign and date the informed consent form; Age between 18 and 65 years old; Have recent (48 hours before study baseline visit) post-traumatic disease (contusion or sprain) of lower or upper limbs (except for fingers and toes), with at least one moderate or more serious symptom of pain or inflammation according to the investigator's evaluation. Exclusion Criteria: Research subjects who meet any criteria below will not be eligible for the study: Have cardiovascular, renal, or hematological disease, diabetes mellitus, gastrointestinal disease, hepatic disease, asthma, rheumatoid arthritis, osteoarthritis, or any other serious chronic comorbidity (at the investigator's discretion); Prior history of gastrointestinal bleeding or ulcers (6 months before enrollment in the study); Have any hemorrhagic disorder; Have apparent complication of bacterial infection; Have a fracture or need of immobilization with cast or surgical procedure or neck sprain; Have a too small area affected (e.g., fingers) not allowing the use of the transdermal patch, skin sores in application site, bad or sensitive condition of the skin with prior history of dermatitis due to the use of topic drugs; Have made a prior (5 days before the study treatment is initiated) or current use of pain medications, NSAIDs, anti-inflammatory drugs, or steroids; Have a known allergy to loxoprofen, inactive ingredients of the formulation or any other NSAIDs; Subjects who are pregnant or breastfeeding or those who want to become pregnant or who refuse to use a safe birth control method during the study; Research subjects who have participated in another clinical study in the last 12 months.

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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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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: transdermal patch & placebo<br>transdermal patch 100 mg once a day for 7 days and placebo (for loxoprofen sodium 60 mg tablet) by mouth, every 8 hours for 7 days | Drug: Transdermal Patch<br>* Transdermal patch 100 mg once a day for 7 days<br>Drug: Placebo (for loxoprofen sodium)<br>* Placebo (for loxoprofen sodium 60 mg per tablet) by mouth, every 8 hours for 7 days<br>|
| Active Comparator: loxoprofen sodium & placebo<br>loxoprofen sodium 60 mg by mouth, every 8 hours for 7 days and placebo (for transdermal patch 100 mg) once a day for 7 days | Drug: Loxoprofen sodium<br>* Loxoprofen sodium 60 mg per tablet by mouth, every 8 hours for 7 days<br>Drug: Placebo (for transdermal patch)<br>* Placebo (for transdermal patch 100 mg) once a day for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score of change in spontaneous pain by using the visual analogue scale (VAS) |  | after seven days of treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of pain evaluated by the VAS scale |  | on day 3 and on day 7 | 
| Impression of the research subject checked by a 7-point scale |  | on day 3 and on day 7 | 
| Evaluation of drug safety as per the occurrence of adverse events and serious adverse events. |  | on day 3 and on day 7, for SAE up to 30 days |