A Clinical Trial to Compare Safety and Effectiveness for Relieving Tenderness of 10% Naproxen Gel vs. a 2.32% Diclofenac Diethylamine Gel in the Treatment of Strains and Bruises of the Legs.

Study Overview
=================
Brief Summary
-----------------
Researchers are looking for a different way to treat people who have an injury to their muscles, ligaments, or tendons in their legs or feet. This is known as a soft tissue injury. Before a treatment is available to all patients, researchers study it in trials to better understand its safety and how well it works. People with soft tissue injuries can have pain, swelling, and bruising. In this trial, the researchers want to learn more about the trial treatment, BAYH006689, in participants with a soft tissue injury to their legs or feet. BAYH006689 is a naproxen gel that is used for the temporary relief of minor aches and pains of muscles and joints. The researchers will learn more about how BAYH006689 works and how safe it is in these participants. The trial will include about 100 male and female participants between the ages of 18 and 60. All the participants will have a soft tissue injury to their legs or feet that was caused by playing sports. The injury will have happened within 3 hours of joining the trial. The researchers will use a computer program to randomly choose what treatment each participant will receive. This will help make sure the treatments are chosen fairly and that comparing the results of the treatments is as accurate as possible. The participants will be randomly chosen to be in 1 of 3 groups: Group 1: 4 grams (g) of BAYH006689 Group 2: 4 g of a diclofenac diethylamine gel Group 3: 4 g of a placebo A placebo looks like a treatment but does not have any medicine in it. Diclofenac diethylamine gel is a treatment already available for doctors to be recommended to people with soft tissue injuries. The participants will receive their treatment once in the evening on Day 1 and then 2 times a day for 4 days. The participants will receive their final dose in the morning of Day 6. The doctors will apply the treatment to the participants' skin where the injury is. The participants must be present at the clinic site 11 times over six days: once on Day 1 and twice daily on Days 2-6. During the trial, the doctors will: check the participants' overall health and ask if they have any medical problems do physical examinations to check the participants' injuries use a device to see how tender and sore the participants' injuries are In this trial, the researchers will study how tender the participants' injuries are after 3 days and at other time points over the 6 day follow-up period. They will also study how many participants have medical problems during the trial.

Official Title
-----------------
Randomized, Controlled, Double-blind, Placebo-controlled, Multi-center Hypothesis-finding Trial to Compare the Efficacy and Safety of a 10% Naproxen Gel vs. a 2.32% Diclofenac Diethylamine Gel and Placebo in the Treatment of Acute Soft Tissue Injuries of the Lower Extremities

Conditions
-----------------
Soft Tissue Injury

Intervention / Treatment
-----------------
* Drug: Naproxen gel
* Drug: Diclofenac gel
* Drug: Placebo gel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent. Participants with a primary diagnosis of acute sports-related acute soft tissue injuries of the lower extremities that do not require hospitalization and that occurred within 3 hours of enrollment. Participants with a baseline algometric measurement values on the injured site of ≤50% of the respective value at the contralateral site. Participants with a baseline pain on movement (POM) of ≥50 mm on a visual analog scale (VAS) (0-100 mm). Participant's absolute sensitivity to tenderness on the contralateral site is at least 2.5 N/cm2 as measured by algometry. Participant's size of trauma is between 25 and 150 cm^2. Exclusion Criteria: Heart surgery within 2 weeks of enrollment in the study. Suspected bone fracture or torn ligaments related to the injury. Open wounds to the area to be treated. Current skin disorders or localized infection in the area to be treated. Injured area is too hairy for proper assessments. Suspected head injury. History of blood coagulation disorders. Current or past history of gastrointestinal ulceration, gastrointestinal bleeding or other bleeding disorder(s). Relevant concomitant disease such as asthma (exercise induced asthma is permitted). History of significant disease deemed by the investigator to render the patient unsuitable for inclusion, including evidence or history of clinically significant (in the judgment of the investigator) hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including hypertension and cardiac arrhythmia), hepatic, psychiatric, neurologic diseases, or malignancies within the last 5 years. Participants with a medical disorder, condition, or history of such that could impair the participant's ability to participate or complete this trial in the opinion of the investigator. Significant ongoing painful condition other than that associated with the sports-related injury/contusion. Any ongoing condition that might interfere with the absorption, distribution, metabolism, or excretion of the study medication. Females who are planning to become pregnant, are pregnant or lactating. Prior/Concomitant Therapy Ice and compression are prohibited from the time of injury through the final evaluation. Physical therapy or other comfort measures, or herbal preparations for bruises from the time of injury through the final evaluation. Use of any medications within 5 days of enrollment until discharge from the study site (except oral contraceptives, prophylactic antibiotics, synthetic thyroid hormones, methylphenidate or medications to treat benign conditions such as antibiotics to treat acne). Any other treatment or medication (oral or topical), that could interfere with the trial (e.g. corticosteroids) up to 3 days prior to the trial. Participants with the following medical conditions may be eligible at the discretion of the investigator: ADHD on a stable dose regimen of methylphenidate/(dextro) amphetamine for at least 6 months; participants with hypothyroidism on a stable dose of synthetic thyroid hormone for at least 6 months. Have received any form of treatment in the form of medication for depression in the past 6 months or any form of psychotropic agent (including selective serotonin uptake inhibitors [SSRI] but excluding ADHD medications described above) within the last 6 months. Any previous history of allergy or known intolerance to naproxen, diclofenac, paracetamol or any of the drugs or formulation constituents which, in the investigator's opinion, might preclude use of an NSAID, including aspirin-sensitive asthma or a previous allergic response to a NSAID, including bronchospasm, urticaria, angioedema, and rhinitis; participation in a clinical trial in the previous 30 days. Use of any over the counter (OTC) or prescription medications with which the administration of naproxen, acetaminophen, any other NSAID, is contraindicated. Habituation to analgesic drugs including opioids (i.e., routine use of oral analgesics 5 or more times per week for greater than 3 weeks within the past 2 years). Other Exclusions More than low-risk alcohol consumption (>24 g (males) or ˃12 g (females) of alcohol regularly per day). Amount corresponds to 0.6 L of beer/day or 0.24 L of wine/day or 3 glasses (at 2 cL) of liquor/day for males and 0.3 L of beer/day or 0.12 L of wine/day or 1 glass (at 2 cL) of liquor/day for females. Self-reported drug abuse within two years prior to screening. Member or first-degree relative of study staff or the Sponsor directly involved in the study. Unwilling or unable to comply with all requirements outlined in the protocol. Previous enrollment in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naproxen Topical Gel (BAYH006689)<br>UI Number: 1614000-268; Subjects will be randomized into one of the three treatment groups in a 2:2:1 (active:active:placebo) allocation. Treatment consists of a twice daily (bid) application (approximately 12 hours apart) of the assigned topical gel over 5 consecutive days, beginning on the evening of Day 1 and ending (last application) on the morning of Day 6 (total of 10 applications). In order to assure adequate representation of different types of soft tissue injuries, at least 25 randomized subjects must enter the study with a lower extremity sprain/strain injury (cohort) and at least 50 randomized subjects with a lower extremity contusion injury (cohort). | Drug: Naproxen gel<br>* 10%, bid for 5 days (final application on morning of Day 6)<br>|
| Active Comparator: Diclofenac Diethylamine Gel<br>UI Number: Not applicable; Subjects will be randomized into one of the three treatment groups in a 2:2:1 (active:active:placebo) allocation. Treatment consists of a twice daily (bid) application (approximately 12 hours apart) of the assigned topical gel over 5 consecutive days, beginning on the evening of Day 1 and ending (last application) on the morning of Day 6 (total of 10 applications). In order to assure adequate representation of different types of soft tissue injuries, at least 25 randomized subjects must enter the study with a lower extremity sprain/strain injury (cohort) and at least 50 randomized subjects with a lower extremity contusion injury (cohort). | Drug: Diclofenac gel<br>* 2.32% bid for 5 days (final application on morning of Day 6)<br>|
| Placebo Comparator: Placebo Gel<br>UI Number: 1614000-272; Subjects will be randomized into one of the three treatment groups in a 2:2:1 (active:active:placebo) allocation. Treatment consists of a twice daily (bid) application (approximately 12 hours apart) of the assigned topical gel over 5 consecutive days, beginning on the evening of Day 1 and ending (last application) on the morning of Day 6 (total of 10 applications). In order to assure adequate representation of different types of soft tissue injuries, at least 25 randomized subjects must enter the study with a lower extremity sprain/strain injury (cohort) and at least 50 randomized subjects with a lower extremity contusion injury (cohort). | Drug: Placebo gel<br>* bid for 5 days (final application on morning of Day 6)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tenderness (Algometry) over the initial 72 hours of naproxen topical gel 10% (BAYH006689) | To assess the effectivenss of a naproxen topical gel 10% for relieving tenderness to pressure in subjects with acute soft tissue injuries of the lower extremities. Algometry will be performed at baseline and at each study visit. Algometric measurements will be performed using a calibrated caliper with digital pressure recording). Increases in pressure during measurement will be kept constant at 10 N/cm2/s. The site of measurement will be marked with a water resistant marker, and measurements will be repeated at the same site. The measurements will be performed in such a way that the patient and the investigator cannot read the actual pressure exerted (covered display). The device stores the last exerted pressure, which is then recorded on the case report form. A tenderness reaction is defined as the pressure that, under the above conditions, produced a painful sensation. | Up to 72 hours post dose | 
| Tenderness (Algometry) over the initial 72 hours of diclofenac diethylamine gel 2.32% | To assess the effectivenss of a diclofenac diethylamine 2.32% for relieving tenderness to pressure in subjects with acute soft tissue injuries of the lower extremities. Algometry will be performed at baseline and at each study visit. Algometric measurements will be performed using a calibrated caliper with digital pressure recording). Increases in pressure during measurement will be kept constant at 10 N/cm2/s. The site of measurement will be marked with a water resistant marker, and measurements will be repeated at the same site. The measurements will be performed in such a way that the patient and the investigator cannot read the actual pressure exerted (covered display). The device stores the last exerted pressure, which is then recorded on the case report form. A tenderness reaction is defined as the pressure that, under the above conditions, produced a painful sensation. | Up to 72 hours post dose | 
| Tenderness (Algometry) over the initial 72 hours of placebo gel | To assess the effectivenss of a placebo gel for relieving tenderness to pressure in subjects with acute soft tissue injuries of the lower extremities. Algometry will be performed at baseline and at each study visit. Algometric measurements will be performed using a calibrated caliper with digital pressure recording). Increases in pressure during measurement will be kept constant at 10 N/cm2/s. The site of measurement will be marked with a water resistant marker, and measurements will be repeated at the same site. The measurements will be performed in such a way that the patient and the investigator cannot read the actual pressure exerted (covered display). The device stores the last exerted pressure, which is then recorded on the case report form. A tenderness reaction is defined as the pressure that, under the above conditions, produced a painful sensation. | Up to 72 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with at least one TEAE after treatment with naproxen topical gel 10% (BAY117031) | TEAE = treatment emergent adverse event | Up to 120 hours post dose | 
| Percentage of subjects with at least one TEAE after treatment with diclofenac diethylamine gel 2.32% |  | Up to 120 hours post dose | 
| Percentage of subjects with at least one TEAE after treatment with placebo gel |  | Up to 120 hours post dose |