Counterpain PXM Versus Diclofenac Versus Piroxicam

The primary goal is to demonstrate that a gel containing the active ingredients Piroxicam plus Counterirritant is equally effective and safe as two other widely used gels in reducing pain. The three gels being compared are:

• Test Gel: Piroxicam plus Counterirritant (brand name Counterpain® PXM). This gel combines an anti-inflammatory drug (Piroxicam) with ingredients that create a distinct warming or cooling sensation on the skin (methyl salicylate, eugenol, and menthol).
• Comparator Gel A: Piroxicam gel only (brand name Pirofel®). This gel contains the anti-inflammatory drug Piroxicam by itself.
• Comparator Gel B: Diclofenac gel (brand name Hotin® DCL). This is another very common and well-studied anti-inflammatory gel, often considered a standard treatment for this type of pain.

The study's central hypothesis is that the Piroxicam-plus-counterirritant gel is not inferior to the other two and provides a similar level of pain relief and safety. This type of study is called an equivalence trial.

How is the Study Designed?

This is a Phase 3, Randomized, Controlled, Multi-center, Single-blind, Parallel-group study. Here's what each of these terms means:

• Phase 3: This is a confirmatory stage of research, often done after a product is already on the market, to confirm its effectiveness and safety in a larger group of people compared to standard treatments.
• Randomized: Participants will be assigned to one of the three gel groups purely by chance, using a computer-generated list (like flipping a coin). This randomization is the best way to ensure the three groups are comparable at the start of the study, minimizing bias in the final results.
• Controlled: The test gel (Piroxicam plus Counterirritant) is being compared against two "control" groups who are using other known and accepted treatments (Piroxicam-only and Diclofenac gels).
• Multi-center: The study will take place at two different clinic locations: Klinik Utama Eminence and St. Carolus Sports Clinic by Eminence. This helps in recruiting enough participants and makes the results more generalizable to the wider population.
• Single-blind: In this type of study, the participants do not know which gel they are using. To achieve this, all the original gel tubes will be completely covered with a plain white sticker, hiding their brand identity. They will only have a study label with a unique code. This prevents the participants' expectations (e.g., thinking a particular brand works better) from influencing how they report their pain. The doctors and physiotherapists who assess the participants will also not know which gel corresponds to which code, ensuring their evaluations are objective. Only the study coordinator and the principal investigator will have access to the master list that links the codes to the actual gels.
• Parallel-group: This means that each participant will only use one type of gel for the entire duration of the study. They will not switch to another gel.

How Long Will the Study Last for Each Person?

The total duration of participation for each individual is 6 ± 1 days. This means the study period could be anywhere from 5 to 7 days. During this time, participants will need to visit the clinic three times:

• Visit 1 (Day 0): The initial screening, enrollment, and first treatment visit.
• Visit 2 (Day 3 ± 1 day): A follow-up visit about halfway through the study.
• Visit 3 (Day 6 ± 1 day): The final visit to conclude the study.

Who Can Take Part in the Study? (Inclusion and Exclusion Criteria) To ensure the study is fair, safe, and that the results are clear and reliable, only people who meet very specific requirements can participate.

Inclusion criteria

(who can join):

• Outpatients at one of the two study clinics.
• Adults aged 18 to 60 years old.
• Diagnosed with acute (sudden-onset) musculoskeletal pain. This specifically includes:
• Osteoarthritis of a joint, with a severity of Grade 0 to III on the Kellgren-Lawrence scale (a standard way to grade osteoarthritis from X-rays). This means mild to moderate arthritis.
• Specific musculoskeletal disorders such as: Ankle sprain, Patellar tendinitis, Tennis elbow (lateral epicondylitis) & Back pain
• Able to read and understand how to fill out the pain assessment forms and the participant diary.
• Willingly provide written consent to participate in the study by signing the informed consent form.

Exclusion criteria

(who cannot join):

• People with severe osteoarthritis (Grade IV on the Kellgren-Lawrence scale).
• Those who have recently had certain medical procedures on the affected joint (e.g., draining fluid, joint injections).
• Individuals currently taking strong painkillers (opioid analgesics) or blood thinners (like warfarin, clopidogrel).
• Those who have taken oral corticosteroids in the 3 days before the study starts.
• People with certain medical conditions, including: Neuropsychiatric disorders (depression, dementia, etc.), Severe, uncontrolled hypertension (high blood pressure), Acute peptic ulcers, Bronchial asthma or a history of aspirin-induced asthma, A known allergy or hypersensitivity to NSAIDs (like piroxicam, diclofenac, or aspirin), Serious liver, kidney, heart, blood disorders, or cancer, Skin conditions (dermatitis) or wounds at the area where the gel would be applied.
• Women who are pregnant, planning to become pregnant, or are currently breastfeeding.
• Anyone considered by the investigator to be unsuitable for the study for any other reason.

What Will Happen During the Study Visits? The process is carefully structured for each of the three visits. This ensures consistency and that all necessary data is collected correctly.

Visit 1 (Day 0 - The Start):

Registration & Screening: A person with pain registers at the clinic. The research team explains the study in detail. If interested, the participant reads and signs the Informed Consent Form, a document confirming they understand the study and voluntarily agree to take part.

Initial Assessments:

• The participant fills out a questionnaire about their pain (the "Brief Pain Inventory" - Form 2).
• A doctor (Principal Investigator or Sub-Investigator) performs a medical interview and physical exam. This includes checking the location and nature of the pain, measuring the Range of Motion (ROM) of the affected joint and testing muscle strength (Form 6). If clinically needed, an X-ray may be taken.
• Randomization & First Treatment: The study coordinator uses a computer to randomly assign the participant to one of the three gel groups.
• The participant receives their first application of the gel from a physiotherapist in the therapy room. The physiotherapist records this (Form 7).
• Immediately after the gel is applied, the participant fills out a short form about the thermal sensation they feel (e.g., cool, warm, neutral, hot) and how long it took to feel that sensation (Form 8).
• Physiotherapy: The participant receives a standardized physiotherapy session based on their specific diagnosis. For example, a person with an ankle sprain will do different exercises than someone with back pain. This session is documented by the physiotherapist (Form 9).

Take-Home Kit: The participant is given a pouch containing everything they need for the next few days:

• 2 tubes of their assigned study gel.

• 3 dosing cards (to help measure the correct amount of gel each time).

• 4 strips of rescue medication (paracetamol 600mg tablets).

• A participant diary to record gel applications, pain levels, and any other medications taken. Business cards for the study coordinator and doctor.

At Home (Between Visits):

• The participant applies the gel at home three times a day (morning, afternoon, evening) using the dosing card.

• They record each application and any changes in their pain in the diary.

• The study coordinator will send daily reminders (e.g., by phone or text) to help with compliance.

• If the pain becomes unbearable, the participant can take the paracetamol (rescue medication) and must record the date and time in the diary.

Visit 2 (Day 3 ± 1 day - The Midpoint):

• The participant returns to the clinic, bringing back their pouch with all remaining products and their completed diary.

• They re-register and meet with the doctor. The same assessments from Visit 1 are repeated (pain questionnaires, ROM, muscle strength).
• They receive another physiotherapy session and another application of their assigned gel from the physiotherapist. They again fill out the thermal sensation form.
• They are given a new pouch with a fresh supply of study gel, dosing cards, and rescue medication to continue the treatment at home until the final visit.

Visit 3 (Day 6 ± 1 day - The End):

• The process is the same as Visit 2.
• The participant returns all remaining products and the completed diary for the final time.
• After the final assessments and physiotherapy session, the doctor informs them that the study is complete.

Inclusion criteria

• Outpatient in a health care setting.
• Between the ages of 18 - 60 years of either sex.
• Patients diagnosed with musculoskeletal pain as described in the target population.
• Patient can read and understand how to fill out the assessment form and diary.
• Patients gave written consent to participate in the study independently.

Exclusion criteria

• Patient who has osteoarthritis with Grade IV Kellgren-Lawrence (KL) grading. - - Patients who underwent any of the following treatments:
• Paracentesis and drainage of joint
• Intraarticular injection (joint protection agents, local anesthetic, etc.)
• Nerve block (including trigger points)
• Patients are being treated with an analgesic opioids for their musculosceletal pain.
• Patients being treated with anti coagulant therapy such as warfarin, clopidogrel.
• Patients being treated with oral corticosteroids 3 days before and until signed the informed consent.
• Patients being treated using rigid orthoses those requiring such treatment
• Patients with neuropsychiatric disorders including depression, dementia, schizophrenia, and anxiety neurosis
• Patients with Grade 3 hypertension (systolic blood pressure ≥ 180 mmHg and diastolic blood pressure ≥ 110 mmHg regardless of the use of an antihypertensive drugs)
• Patients with acute peptic ulcer
• Patients with bronchial asthma with current or previous aspirin-induced asthma (asthmatic attacks induced by NSAIDs and other relevant drugs)
• Patients with a history of hypersensitivity or allergy to NSAIDs
• Patients with serious hepatic disease, renal disease, cardiac disease, hematologic disease, or malignancy
• Patients with a history of dermatitis requiring treatment with topical agents
• Patients with dermatitis or wounds at the application site of the study drug
• Pregnant women ,women who may be pregnant, women who wish to become pregnant during the study, or nursing women
• Patients considered by the Investigator to be inappropriate as participants of this study