Efficacy & Safety of Piroxicam Plus Counterirritant Gel Compared With Other Topical Non-Steroid Anti-Inflammatory Drugs in Managing Musculoskeletal Pain: A Randomized Clinical Study
Phase: PHASE3
Conditions: Ankle Sprain, Back Pain, Osteoarthritis (OA) of the Knee, Tennis Elbow, Runner's Knee
Sponsor: Taisho Pharmaceutical Indonesia

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CLINICAL STUDY PROTOCOL 
 
EFFICACY & SAFETY OF PIROXICAM PLUS COUNTERIRRITANT GEL 
COMPARED WITH OTHERS TOPICAL NON-STEROID ANTI 
INFLAMMATION DRUGS IN MANAGING MUSCULOSKELETAL PAIN : 
A RANDOMIZED CLINICAL STUDY 
NO. PROTOCOL : CT_CTPPXM001_PRT_V003/IX/2025 
Approved on 08 September 2025 
 
 
Clinical Research Team  
dr. Erica Kholinne, Sp.OT (K), Ph.D 
dr. Astuti Pitarini, Sp.OT (K) 
dr. A. Andi Kurniawan, Sp.KO Subsp. ALK (K) 
dr. Wawan Budisusilo, Sp.KO 
dr. Marion Cinta Kuntjoro, Sp.KFR 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Supported by:  
PT Taisho Pharmaceutical Indonesia TBK 
2025 
 

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History of CT_CTPPXM001 protocol changes as follows:  
Protocol Version 
Description 
CT_CTPPXM001_PRT_V001/II/2025 
This is the first protocol that was reviewed by Clinical 
Research Team,  TPI and TPI’s consultant 
CT_CTPPXM001_PRT_V002/VI/2025 Protocol V001 has been revised to refer to BPOM RI 
Letter about Additional data and Protocol revision No. 
B-RG.01.06.32.323.5.2025.1759 on May 29th 2025. 
The revisions that applied in the PRT V002 are:  
- 
The tittle of clinical study 
- 
The clinical study background and justification 
of the study 
- 
The study objective 
- 
The study design 
- 
The inclusion criteria 
- 
The sample size 
- 
The investigational products 
- 
The study schedule 
CT CTPPXM001 PRT V003/IX/2025 
Protocol V002 has been revised to refer to the 
discussion with BPOM RI on Aug 9th 2025.  
The clinical study was conducted with the main aim of 
developing education and health standards in 
Indonesia. Thus, the concept of clinical study will be 
an Investigator Initiated Trial (IIT). 
 
Add secondary objective point : 
- 
Time (in days) musculoskeletal pain symptoms 
dissapear. 
 
 
 
 
 
 
 
 
Changes to this protocol have been reviewed and acknowledged by:  
Sponsor 
PT Taisho Pharmaceutical Indonesia 
Clinical Research Team 
 
 
 
 
 
 
08 September 2025 
dr. Ardini Kartasasmita 
Medical Manager 
 
 
 
 
 
 
 
08 September 2025 
Aryani Pratami Dewi 
Head of Regulatory Affairs and 
Medical  
 
 
 
 
      08 September 2025 
dr. Erica Kholinne, Sp. OT (K), Ph.d 
Principal Investigator 

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PROTOCOL SIGNATURE PAGE 
 
  Clinical Research Team:  
 
 
I agree to conduct the study in accordance with this Protocol and in 
compliance with all applicable Health Authority requirements, Good 
Clinical Practice and National Laws. 
 
 
Name & Position 
 
Signature & Date of Signature 
 
dr. Erica Kholinne, Sp.OT (K), Ph.D 
Principal Investigator 
 
 Signature: 
 
 
Date: 8 September 2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. GENERAL INFORMATION 

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Clinical Study Tittle  
: Efficacy and safety of Piroxicam Plus Counterirritant gel 
compared with others Topical Non Steroid Anti Inflammation 
Drugs in Managing Musculoskeletal Pain: a randomized clinical 
study.  
Clinical Study Phase  
: Phase III 
Protocol Number 
 
: CT_CTPPXM001_V003/IX/2025 
Protocol Date Version 
: V003- 08 September 2025 
Principal Investigator  
: dr. Erica Kholinne, Sp.OT (K), Ph.D 
Sub-Investigator 
 
:  
1) dr. Astuti Pitarini, Sp.OT (K) 
2) dr. A. Andi Kurniawan, Sp.KO Subsp. ALK (K) 
3) dr. Wawan Budisusilo, Sp.KO 
4) dr. Marion Cinta Kuntjoro, Sp.KFR 
 
Sites 
 
 
 
: Sports Medicine Clinic 
1) Klinik Utama Eminence  
2) St. Carolus Sports Clinic by Eminence 
 
Sponsor 
 
 
: PT Taisho Pharmaceutical Indonesia TBK 
Millenium Centennial Center 8th Floor,Jalan Jend.Sudirman 
Kav. 25 Jakarta 
 
Monitoring 
: The monitoring of this clinical study will be conducted by 
certified Clinical Research Associates that appointed by Sponsor 
 
 
 
2. CLINICAL STUDY BACKGROUND 
 
2.1 Piroxicam Plus Counterirritant gel 
In 1972, an innovator topical analgesic product was introduced to the Indonesian market. 
Counterpain® is one of the topical analgesic products that is known not only in Indonesia, but 
also in other Southeast Asian countries such as Malaysia, Philippines, and Thailand. 
Counterpain® as an innovator product in Indonesia has several variants, namely Counterpain® 
cream helps with a warm sensation that relieve muscle pain, Counterpain® Cool with a cool 
sensation can be used for cooling during exercise and Counterpain® PXM effectively relieves 
inflammation in musculoskletal and joint. 
 
There are many topical preparations containing non-steroidal anti-inflammatory drugs, namely 
diclofenac, ketoprofen and also piroxicam. Piroxicam preparations that are registered as 
innovator products in Indonesia :  
• Feldene® gel which only contains Piroxicam as an active substance and  
• Counterpain® PXM which contains Piroxicam, and Counterirritant: methyl salicylate, 
menthol and eugenol as active substances.  
Counterpain® PXM was first registered and obtained marketing authorization in Indonesia in 
2004 by Bristoll Myers Squibb (BMS). The registration process was completed  by providing 
research data of Counterpain PXM-Thailand clinical study in 1995 as supporting data. 

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The pharmacokinetic parameters of  piroxicam 0.5% topical gel were taken from data were 
determined in 20 healthy volunteers (6 women and 14 men) following application of multiple 
doses (20 mg piroxicam daily) over 14 days. 21 blood samples were drawn from each patient 
beginning just before application of the first dose, with the final sample taken 14 days after 
application of the last dose. Plasma concentrations of piroxicam were determined by high-
performance liquid chromatography using UV detection at 340nm. There was considerable 
interindividual variation in piroxicam half-lives with a mean of 79 hours. Mean piroxicam 
plasma concentrations at steady-state were between 300 and 400 ng/ml, which is about 5% of 
those observed after equivalent doses of oral or intramuscular piroxicam. No adverse 
experiences were reported during the study period. Thus, the results of this study confirm the 
minimal systemic absorption of piroxicam during multiple-dose application of the 0.5% topical 
gel and the excellent tolerability of this mode of piroxicam therapy. 
 
A study that conducted in 1995, with its tittle “The study of efficacy and safety of anti 
inflammatory and analgesic cream in the treatment of musculoskeletal pain” described that the 
standard piroxicam gel 0.5 % versus the test drug, piroxicam and analgesic cream containing 
methylsalicylate, eugenol and menthol are equally effective and well tolerated in the treatment 
of musculoskeletal pain. It was interesting to note that most of patients prefer to have the warm 
feeling after application as it indicates that the medication was working.  
 
Another study that conducted in 1995, with its tittle “A double-blind randomized study to 
evaluate the safety and effectiveness of 0.5% Piroxicam gel compared to Counterpain Plus 
(combination of 0.5% piroxicam gel, 10% methyl salicylate, 5.4% menthol and 1.36% eugenol) 
in patients with mild osteoarthritis. As conclusion that both Counterpain Plus and Piroxicam 
gel are equally effective in gradual relief of the knee joint pain that assessed by Visual Analog 
Scale or Verbal Rating Scale. Both also equally effective help restore the patient’s functional 
ability.  
 
The last study that executed in 1995 with its tittle “Comparative study of the clinical effects of 
Counterpain Plus and Feldene Gel on knee arthrosis”, found that there was no difference 
between the terms of biographic data, stage of degeneration, Moberg’s functional scores and 
severity of pain between the groups at pre-trial and the end of the study. Counterpain Plus and 
Feldene gel have comparable clinical effects on the treatment of knee arthrosis.  
 
In 2009, Taisho Pharmaceutical Holdings acquired the commercial rights of Counterpain in 
Indonesia. The distribution permit for the Counterpain® PXM product was transferred to PT 
Taisho Pharmaceutical Indonesia thereafter. Counterpain® PXM as a topical non-steroid anti 
inflamation drugs (NSAID) Plus Counterirritant such as methyl salicylate, eugenol and 
menthol, can be used to help relieve musculoskeletal pain and inflamation such as 
osteoarthritis, acute post-traumatic disorders: tendinitis, tenosynovitis, periarthritis, strain, 
sprain, muscle tense and low back pain, this indication is approved by BPOM RI in 2011.  
 
There are no recent clinical studies in 2000 onwards that examine the efficacy of Piroxicam 
plus Counterirritant gel in the treatment of musculoskeletal pain compare with others topical 
NSAIDs such as Diclofenac gel or Ketoprofen gel.  
 
 
2.2 Justification to conduct clinical study 
Acute musculoskeletal pain describes conditions like a sprained ankle or a muscle pull. These 
usually get better over two or three weeks without treatment, but can be very painful while they 

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last. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are applied to unbroken skin 
where it hurts as gels, creams, sprays, or plasters. Topical NSAIDs penetrate the skin, enter 
tissues or joints, and reduce processes causing pain in the tissue. Drug levels in the blood with 
topical NSAIDs are very much lower than with the same drug taken by mouth. This minimises 
the risk of harmful effects. 
 
The review from Cochrane in 2019, “Topical NSAIDs for acute musculoskeletal pain in 
adults”, formulations of topical diclofenac, ibuprofen, ketoprofen, piroxicam, and 
indomethacin demonstrated significantly higher rates of clinical success (more participants 
with at least 50% pain relief) than matching topical placebo (moderate or high quality data). 
From the 42 clinical studies data that taken into the systematic reviews, 15 studies are discussed 
about Diclofenac, and only 3 studies discussed about efficacy of Piroxicam gel in 
musculoskletal pain. None of those data explained about Piroxicam gel plus Counteriiritant.  
 
Another review from Global Pain Faculty “The burden of musculoskeletal pain and the role of 
topical non-steroidal anti-inflammatory drugs (NSAIDs) in its treatment. Ten underpinning 
statements from a global pain faculty”, published on Current Medical Research and Opinion, 
2021, presents the conclusions of a detailed discussion on the role of topical NSAIDs during a 
round table Global Pain Faculty meeting held in Amsterdam in 2019 and subsequent 
discussions online. The document considers the place of topical therapies alongside other 
pharmacological and non-pharmacological treatments and presents the evidence for the 
benefits and harms of topical NSAIDS including indicators of efficacy for three main topical 
NSAIDs– diclofenac, ibuprofen and ketoprofen – based on almost 15,000 participants in 
randomized controlled trials for acute and chronic musculoskeletal pain. Randomized 
controlled trial evidence suggests that adverse events for active topical NSAIDs are similar to 
placebo. In this review, there is no discussion about effectiveness of Piroxicam gel especially 
Piroxicam gel plus Counterirritant in musculoskeletal pain.  
 
A study that published in 2018, with its title “Relative efficacy and safety of topical non-
steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-
analysis of randomised controlled trials and observational studies”, showed that systematic 
review and network meta-analysis of RCTs and observational studies and have ranked the 
topical NSAIDs (including salicylate) based on the results. Among all available topical 
NSAIDs, diclofenac patches were most effective for pain relief and piroxicam gel was the best 
option to improve function. 
 
By referring to above data from comprehensive review studies and meta-analyses studies, it 
can be seen that diclofenac gel has more clinical studies data compared to piroxicam gel, so 
the use of diclofenac gel for the treatment of musculoskeletal pain can be traced with the 
support of an adequate clinical data whereas this data becomes the basis for selecting standard 
topical drugs for musculoskeletal pain. 
 
For this reason, a clinical study will be conducted to compare the effectiveness of Piroxicam 
plus Counterirritant gel with others topical Non Steroid Anti Inflammation Drugs such as 
Piroxicam gel and Diclofenac gel in the adult population with musculoskeletal pain. This 
clinical data will be used as a standard treatment in management of musculoskeletal pain.  
 
The clinical study will be conducted with the concept of Investigator Initiated Trial (IIT) with 
the purpose to developing education and health standards in Indonesia, the result of study will 
be the source to develop a standard guidance in management of musculoskeletal pain using 

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topical non steroid anti inflammation drugs especially in Eminence and general in all sports 
medicine clinic in Indonesia.  
 
 
3. COMPLIANCE WITH GCP 
This study will be conducted in accordance with Good Clinical Practice (GCP), as defined by 
the International Conference on Harmonization (ICH) and in accordance with Indonesian 
National Agency for Drug and Food Control Guidance (Pedoman Cara Uji Klinik yang Baik - 
CUKB). The principal investigator shall conduct this study after agreeing with the sponsor on 
the content of the protocol of this study and the case report form and compliance with them. 
 
 
 
4. STUDY OBJECTIVES 
The objectives of this study is to demonstrate the equivallency of efficacy and safety  in 
reducing muskuloskeletal pain between Piroxicam plus Counterirritant gel versus Piroxicam 
gel and Diclofenac gel,  applied for 6 + 1 days in Indonesian population.  
 
Justification: 
Piroxicam plus Counteriiritant,  Piroxicam, Diclofenac are considered as topical Non-Steroid 
Anti Inflammantory Drugs (NSAIDs). Diclofenac more common to use as a standard topical 
treatment since they have more clinical studies data than others topical NSAIDs. To 
demonstrate that Piroxicam plus Counterirritant has the same efficacy with Piroxaicam, 
Diclofenac, the dedicated clinical study need to be conducted.  
 
 
5. STUDY DESIGN 
This is a Phase 3, Randomized Control Trial, Multi centre, Single-blind, and Parallel group of 
6 + 1 days  duration of data collection after topical application to compare the efficacy and 
safety of standard treatment of musculosceletal pain in adult populations. 
Justification : 
• Phase 3 (Confirmatory study)  
The study is conducted to demonstrate whether or not a product offers a treatment 
benefit to adult participants with musculoskeletal pain between test drug (Piroxicam 
plus Counterirritant) and commonly used NSAID topical products, Piroxicam gel, 
Diclofenac gel 
• Randomized Control Trial (RCT) 
Participants are randomly assigned to different treatment or control groups to minimize 
bias and allow for causal inference.  
• Multi centre 
The study will be conducted in 2 sites 
• Single-blind 
To keep this study maintain the integrity of the data, the investigational product will be 
given a white sticker to cover all over the tube of investigational products. On top of 
the tube, there is a study label with unique code to differentiate the test drug and 
comparator drug. With this procedure, participants will not know which products that 
assigned to them. Therefore participants can be blinded.  
• Parallel 

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The study in which two groups of participants receive Piroxicam plus Counterirritant 
gel or Piroxicam gel, or Diclofenac gel . Participants are assigned to one of the treatment 
arms at the beginning of the trial and continue in that arm throughout the length of the 
trial. Assignment to a group usually is randomized. 
 
5.1 Primary End-Point:  
The primary end-point is the  difference of musculoskeletal pain reduction > 3 scores , of the 
response to treatment that can be seen through Brief Pain Inventory (BPI) scores.   
Justification: 
• The Brief Pain Inventory (BPI) scores.  
It is a medical questionnaire that is used to assess pain. It has also been validated for pain 
assessment chronicle. There are 9 questions related to the pain experienced by the participants. 
The pain assessment will be given in the form of a score, namely a score of 0 - 10. 
Score 0 
 
: No Pain 
 
Score 1 – 3  
: Mild Pain 
 
Score 4 – 6  
: Moderate Pain 
 
Score 7 – 10  : Severe Pain 
The difference BPI scale >  3 , from initial scale of pain to the end of treatment will be captured 
as the primary efficacy endpoint. 
The selection of difference more than equal to 3 was chosen because if the participant has 
moderate pain at the beginning of the treatment, then at the end of the treatment there is a 
decrease in pain to mild pain. This can be seen that the treatment is effective in dealing with 
musculoskeletal pain. 
 
5.2 Secondary End-Point: 
1) In data related to safety assessment, the number of participants who experienced 
adverse events (including serious adverse events) with each symptom present will be 
recorded and causality of adverse events and serious adverse events assesses with the 
help of Naranjo’s algorithm 
Justification: 
At the 1st visit, participants will bring home Participant’s Diary. Participants need to fill in if 
they experienced with others symptoms after get the treatment. Also they need to file the rescue 
medication that they consume during the study timeline. On the 2nd visit and last visit the 
Investigator will ask about the diary and confirmed the symptoms and medication. When there 
is safety report, the Investigator will fill in the Safety Form from BPOM RI (Form Kuning 
MESO) and assess the safety events with the help of Naranjo’s algorithm.  
The type of symptoms and the number of participants who have symptoms and including side 
effects will be recorded and become data related to product safety. 
 
2) Investigator Assessment on Participants motions, through Range of Motion (ROM) and 
Muscle test. 
Justification: 
One of the symptoms that must be assessed when there is musculoskeletal pain is the range of 
motion and muscle movement to perform an activity. Therefore, an assessment for the 
examination of the range of motion and muscle strength carried out by the examining doctor is 
needed to determine the effect of the treatment carried out in the success of performing the 
activity. 
The effectiveness of the treatment will be seen from the progress in the range of motion that 
can be performed by the participant at the end of the treatment compared to the beginning of 
the treatment according to scientific standards.  

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Range of motion (ROM) or motion arc in this study will be measured using a universal 
goniometer following standardized procedures to ensure accuracy and reproducibility. Each 
joint will be assessed in a consistent anatomical position—either supine, seated, or standing—
depending on the specific joint involved (e.g., seated for elbow, supine for knee). The Principal 
Investigator or Sub-Investigator will perform three consecutive measurements for each motion 
(e.g., flexion, extension), and the average value will be recorded. Key movements assessed will 
include knee flexion-extension, ankle dorsiflexion-plantarflexion, elbow flexion-extension, 
and lumbar spine flexion or fingertip-to-floor distance for back pain. The same assessor will 
conduct all measurements at each time point to minimize inter-rater variability. Any limitations 
due to pain, guarding, or compensatory movements will be noted. ROM data will be recorded 
on standardized forms and used to evaluate treatment effectiveness by comparing baseline to 
post-treatment values against established minimal clinically important difference (MCID) 
thresholds. 
 
In this study, the minimal clinically important difference (MCID) for joint range of motion 
(ROM) will be used to define clinically meaningful improvements in mobility following 
treatment. Based on validated references, the MCID values applied are ≥ 10° for knee 
flexion/extension (Mizner et al., 2005) and elbow flexion-extension arc (Picha et al., 2020), ≥ 
5° for ankle dorsiflexion/plantarflexion (Cleland et al., 2013), and either ≥ 10% change or ≥5 
cm improvement for lumbar spine mobility, depending on the measurement method used 
(Stratford et al., 1994). These thresholds represent the minimum degree of change perceived as 
beneficial by patients and are appropriate benchmarks for evaluating functional recovery in 
musculoskeletal pain conditions. 
 
3) Assessment to investigate scales on thermal sensation, thermal comfort, and thermal 
acceptance using ASHRAE 7-point scale quistionnaire and completed with time 
starting the thermal sensation.  
Definition: 
Thermal comfort is the condition of mind that expresses satisfaction with the thermal 
environment and is assessed by subjective evaluation. 
Thermal sensation is assessed to determine whether a specific thermal condition can be 
considered comfortable or not. The most prominent scale used for the assessment of thermal 
sensation is the ASHRAE 7-point scale, which consists of seven verbal anchors: “cold”, “cool”, 
“slightly cool”, “neutral”, “slightly warm”, “warm”, and “hot”. 
Thermal acceptance, refers to the degree to which a temperature range or condition is 
considered acceptable or tolerable by individuals.  
The number of thermal sensations felt related to the product will be the result related to the 
participant's acceptance of the sensation.  
 
4) Assessment to investigate the disapperance time of musculoskletal pain (in days). 
Definition:  
To know the medication given is effective or not, we need to evaluate the musculoskeletal pain 
score. One of the result that can be seen is the disappearance time of musculoskletal pain.  
 
6. PARTICIPANTS 
In selecting participants, Investigator shall carefully examine whether or not it is appropriate 
to ask for participation in the study, paying attention to matters including dependence on the 
principal investigator or other personnel, from the perspective of protection of human rights. 

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Among patients who have “Target Disease,” those who meet “Inclusion Criteria” and do not 
meet any of “Exclusion Criteria” will be examined. 
 
6.1 Target Populations 
Participants who were diagnosed with acute musculoskeletal pain will be recruited in this 
study. 
The acute musculoskeletal pain caused by arthritis such as osteoarthritis (OA) with Grade 0 
until III Kellgren-Lawrence (KL) grading, or musculosceletal disorders such as ankle sprain, 
patella tendinitis, tennis elbow, and back pain as mentioned in topical NSAIDs indication that 
approved by BPOM RI.  
Diagnosis criteria were made by history taking, physical examination and radiologic evaluation 
if necessary. 
Justification: 
Acute musculoskeletal pain is defined as pain arising from the musculoskeletal system 
(muscles, bones, joints, ligaments, and tendons) that is sudden in onset and relatively short-
lived. 
• Subject with musculoskletal pain caused by Osteoarthritis, Grade 0 – Grade III 
Kellgren-Lawrence 
Grade 0 
 
 
: No radiographic evidence of osteoarthritis. 
Grade 1 
 (Doubtful) 
: Possible osteophytes (bone spurs) and doubtful joint 
space narrowing. 
Grade 2 (Minimal) 
: Definite osteophytes and possible joint space narrowing. 
Grade 3 (Moderate) 
: Moderate joint space narrowing, multiple osteophytes, some 
sclerosis (increased bone density), and possible bone deformity. 
• Subject with musculoskletal pain caused by musculoskletal disorder, such as : 
Ankle sprain is a common injury that occurs when the ligaments in the ankle are 
stretched or torn due to a sudden twisting or rolling motion of the foot. 
Patellar tendinitis, also known as jumper's knee, is an inflammation of the patellar 
tendon, which connects the kneecap (patella) to the shinbone (tibia). 
Tennis elbow, also known as lateral epicondylitis, is a condition characterized by pain 
on the outer side of the elbow, specifically near the bony prominence (lateral 
epicondyle). It's typically caused by overuse or repetitive motions of the forearm 
muscles, which can lead to tiny tears and inflammation in the tendons that attach these 
muscles to the elbow. 
Back pain, also known as dorsalgia, refers to pain experienced in the back, from the 
base of the neck to the top of the buttocks.  
 
6.2 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. 
6.3 Exclusion criteria 
o Patient who has osteoarthritis with Grade IV Kellgren-Lawrence (KL) grading. 
o Patients who underwent any of the following treatments: 
• Paracentesis and drainage of joint 

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• Intraarticular injection (joint protection agents, local anesthetic, etc.) 
• Nerve block (including trigger points) 
o Patients are being treated with an analgesic opioids for their musculosceletal pain.  
o Patients being treated with anti coagulant therapy such as warfarin, clopidogrel.  
o Patients being treated with oral corticosteroids 3 days before and until signed the 
informed consent.  
o Patients being treated using rigid orthoses those requiring such treatment 
o Patients 
with 
neuropsychiatric 
disorders 
including 
depression, 
dementia, 
schizophrenia, and anxiety neurosis 
o Patients with Grade 3 hypertension (systolic blood pressure ≥ 180 mmHg  and diastolic 
blood pressure ≥ 110 mmHg regardless of the use of an antihypertensive drugs)  
o Patients with acute peptic ulcer 
o Patients with bronchial asthma or those with current or previous aspirin-induced asthma 
(asthmatic attacks induced by NSAIDs and other relevant drugs) 
o Patients with a history of hypersensitivity or allergy to NSAIDs 
o Patients with serious hepatic disease, renal disease, cardiac disease, hematologic 
disease, or malignancy 
o Patients with a history of dermatitis requiring treatment with topical agents 
o Patients with dermatitis or wounds at the application site of the study drug 
o Pregnant women, women who may be pregnant, women who wish to become pregnant 
during the study, or nursing women 
o Patients considered by the Investigator to be inappropriate as participants of this study 
 
6.4 Withdrawal Criteria 
• Any clinical adverse event, serious illness, or other medical condition identified by the 
investigator or treating doctor that suggests continued participation is not in the 
subject's best interest.  
• A voluntary decision by the patient to withdraw from the study.  
• If the subject was found to have entered the study in violation of the protocol or if the 
patient was uncooperative during the study.  
• Any subject who required the use of an unacceptable concomitant medication—defined 
as a medication that interfered with the study—will be addressed with justification from 
the investigator. 
 
6.5 Preparation of Consent Form and Other Written Information for Patients 
The principal investigator prepares the consent form and other written information for 
patients that are used to obtain the consent of participants to participate in the study and 
revise them as necessary, in cooperation with the sponsor. The principal investigator 
submits the prepared or revised documents concerned to the sponsor and obtains prior 
approval of the institutional review board. 
 
6.5.1 Matters That Should be Included in Consent Form and Other Written 
Information for Patients 
The consent form and other written information for patients must include the following 
matters at least. 
o That the study involves research. 

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o Study objectives 
o Names and contacts of the investigators 
o Study methods 
o Anticipated advantages for physical and mental health of participants resulting 
from the study drugs (if such advantages are not expected, to that effect) and 
anticipated disadvantages to participants 
o Presence or absence of other therapeutic methods for the patients concerned and 
the important benefits and risks anticipated in association with these therapeutic 
methods 
o Anticipated duration of participation in the study 
o That participation in the study is voluntary and the participants can reject to 
participate or stop participating in the study any time. That the participants will 
neither be treated unfairly due to such rejection or withdrawal nor lose the 
benefits they should have received for the reason of not participating in the study 
o That monitors, people in charge of audit, institutional review boards and other 
personnel and the regulatory agency can view the source documents related to 
the medical care That subject confidentiality will be protected in such viewing 
That, by signing the consent form, participants agree to the viewing 
o That subject confidentiality will be protected when the study results are 
published 
o Consultation service at the study site participants should make inquires to or 
contact when they wish to have further information regarding the study and their 
rights or when any health hazard associated with the study occurs 
o Compensation and treatment participants can receive when health hazards 
associated with the study occur 
o Anticipated number of participants participating in the study 
o That any information that may influence the intention of participants to continue 
to participate in the study is promptly provided to participants if such 
information was obtained 
o Conditions or reasons for terminating the participation of certain participants in 
the study 
o Details of the expense of participants, if any 
o Details of the payment in cash, etc. to participants, if any 
o Rules that participants should follow 
o Matters regarding the institutional review boards that investigate and deliberate 
the adequacy of this study, including the types of institutional review boards, 
etc. and the matters investigated and deliberated by each institutional review 
board 
 
 
 
6.5.2 Timing and Method of Informed Consent 
Investigator provides sufficient explanation to  before conducting the study, using the 
consent form and other written information for patients, confirms that the participants 
fully understood the explanation, and then obtains written voluntary consent of the 
participants themselves to the participation in the study. Investigator who provided the 

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explanation and the subject write down their names and place their seals on or sign and 
date the consent form.  
Investigator gives a copy of the consent form and other written information for patients 
to the participants who agreed to participate in the study and records it. The above 
receipt of documents can be recorded in a column for receipt prepared in the medical 
record or the consent form. The original consent form is retained at the designated area 
at each study site. 
Investigator enters the date of consent in the case report form. 
 
6.5.3 Points for Consideration in Acquisition of Consent 
The principal investigator, sub-investigator, or clinical research coordinator shall 
consider the following points regarding acquisition of consent. 
• Participants must be neither forced to participate or continue to participate in the study 
nor unduly influenced in their decisions. 
• In the explanation, any phrases that make or appear to make participants waive their 
rights or release or appear to release the principal investigator, sub-investigator, CRC, 
study site, and sponsor from liability must not be used. 
• In the explanation, words that are understandable to participants and as non-technical 
as possible must be used. 
• Before consent, participants must be given a chance to ask questions and sufficient time 
to decide whether to participate in the study. On the above occasion, all the questions 
must be answered to the satisfaction of the participants. 
 
6.5.4 Revision of Consent Form and Other Written Explanation for Patients 
(provision of new information) 
(1) When Investigator obtained new information that may influence the intention of 
participants to continue to participate in the study or may be related to the consent 
of the participants (including reports of serious ADRs), Investigator verbally gives 
the information concerned to the participants immediately and confirms whether or 
not the participants intend to continue to participate in the study. Investigator also 
records the information Investigator has given and the result of confirmation in the 
medical record or other documents. 
(2) In cases described in (1), if the principal investigator acknowledges the necessity of 
revision of the consent form and other written information for patients, principal 
investigator promptly revises the consent form and other written information for 
patients based on the information concerned and newly obtains the approval of the 
institutional review board. 
(3) Investigator provides explanation again using the consent form and other written 
information for patients that were revised according to the rule in (2) to the 
participants including those who already received the information concerned 
verbally and obtains their written consent to continuation of participation in the 
study. However, explanation does not have to be provided to the participants who 
already completed the study.  
 
 
6.6 Subject Enrollment 

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A unique subject IDs will be assigned to each participant by the Investigator at 1st visit. This 
number will serve as the participant’s identifier in the study as well in the study database. This 
subject IDs will be unique across each site and it will be a 5 digit number including last three 
digits will be the subject ID at each site with hyphen between the site number and the last three 
digits. Site number will be assigned by Sponsor. 
 
At the start of the study, the principal investigator assigns participant ID to the participants who 
gave written consent by themselves. Two copies of the screening list of participants that 
includes the information of the participants who gave consent are prepared. One copy is 
retained and the other copy is submitted to the sponsor. Regarding the participants who were 
not enrolled, the reason is recorded. 
 
On the CRFs or other documents submitted to the Sponsor, participants should not be identified 
by their names, but by their assigned subject IDs only. If subject names are included on copies 
of documents submitted to the Sponsor, the names must be obliterated and the assigned subject 
ID added to each of the documents. 
 
 
6.7 Sample Size 
 Assumptions  
- Outcome 
 
 
 
: Pain score 
- Standard deviation (σ) 
 
 
: 1.81  
- Clinically meaningful margin (Δ or δ) 
: 1.0  
- Power 
 
 
 
 
: 80% (Z₁-β = 0.84)  
- Significance level (α) 
 
 
: 0.05  
 
Reference standard deviation from Kocak AO, Dogruyol S, Akbas I, Menekse TS, Gur STA, 
Kocak MB, Cekmen B, Orun S, Cakir Z. Comparison of topical capsaicin and topical 
piroxicam in the treatment of acute trauma-induced pain: A randomized double-blind trial. Am 
J Emerg Med. 2020 Sep;38(9):1767-1771. doi: 10.1016/j.ajem.2020.05.104. Epub 2020 Jun 2. 
PMID: 32739846.  
 
For equivalence trials with 3 groups, you typically plan for pairwise equivalence testing: 
• 
Diclofenac vs. Piroxicam 
• 
Diclofenac vs. PXM plus Counterirritant 
• 
Piroxicam vs. PXM plus Counterirritant 
 
This means you must adjust α to account for multiple comparisons, commonly 
using Bonferroni correction: 
Adjusted α = 0.05 / 3 = 0.0167 → Z₁-α/2 ≈ 2.39 
 
 
 
Sample Size Formula and Calculation 
Using the formula for equivalence trials: 
n = ((Z₁-α/2 + Z₁-β) × σ / Δ)² 
 
Substituting the values: 
n = ((2.39 + 0.84) × 1.81 / 1.0)² 

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n = (4.059 × 1.81)² = (7.35)² = 54.0 
 
Sample size per group (rounded): 54 
Total sample size for 3 groups: 162 
 
With 10% dropout: 
Total = 162 / (1 - 0.10) ≈ 180 participants 
Recommended: 60 participants per group 
 
The clinical study will be recruited in total 180 subjects, which means 60 subjects per arm.  
 
Justification: 
• We used the reference from Kocak et al. because: The study used topical piroxicam, 
which is the main active ingredient in Counterpain PXM. The study was randomized, 
double-blind, and controlled, and reported the standard deviation of pain scores in 
full—a parameter that is essential for sample size calculations. To date, we have not 
found any publications comparing diclofenac gel directly with topical piroxicam, with 
standard deviations appropriate for use in statistical calculations. So, even though the 
comparator was capsaicin, this reference was chosen because it is quite representative 
in terms of pain type and study design. 
 
6.8 Study Drugs 
The specific information about Study Drugs will be described in the Study Drugs Handling 
Manual.  
 
6.8.1 Test Drug : Counterpain® PXM 
• Active Ingredients 
: Piroxicam plus Counterirritant (Methyl Salicylate, Eugenol and 
Menthol) 
• Dose  
 
:  
Adults  
 
: Refer to product’s leaflet as follow: no occlusive dress should 
be employed. Apply gel to the affected area three times daily leaving no residual 
material on the skin. 1 gram of gel ( ~ 3 cm) applied to the affected area. 
The affected areas are:  
o The arms: hand, wrist, elbow, shoulder sinistra or dextra 
o The legs: feet, ankle, knee sinistra or dextra 
o Upper back or Lower back 
3 times daily means: 
o application one time in morning (06.00 – 11.00),  
o one time in afternoon (11.01 – 17.00),  
o one time in evening (17.01 – 23.00). 
Aplication of gel will use dosing cards that provided in this clinical study. 
• Method of administration:  external use only. 
• Every visit, participants will get 2 tubes and in total are 6 tubes for 6 + 1 days 
application.  
Justification: 
The dosage for use refers to the Counterpain® PXM leaflet which has been approved by 
BPOM RI. 
Refer to Counterpain® PXM data that 1 gram equal to 3 cm.  

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6.8.2 Comparator Drug : Hotin® DCL 
• Active Ingredients 
: Diclofenac Diethylamine 11.6 mg (Diclofenac Sodium 10 mg) 
• Dose  
 
: Refer to the product’s leaflet : no occlusive dress should be 
employed. Apply the required amount of cream on the affected area three times a day 
and rub gently. The amount of cream needed depends on the extent of the painful area. 
The affected area are :  
o In the arms: hand, wrist, elbow, shoulder sinistra or dextra 
o In the legs: feet, ankle, knee sinistra or dextra 
o Upper back or Lower back 
3 times daily means : 
o application one time in morning (06.00 – 11.00),  
o one time in afternoon (11.01 – 17.00),  
o one time in evening (17.01 – 23.00). 
Aplication of gel will use dosing card that provided in this clinical study. 
• 
Method of administration: external use only. 
• Every visit, participants will get 2 tubes and in total are 6 tubes for 6 + 1 days 
application 
Justification: 
The dosage for use refers to the HOTIN DCL® leaflet which has been approved by BPOM 
RI 
 
6.8.3 Comparator Drug : Pirofel® gel 
• Active Ingredients 
: Piroxicam 0.5% 
• Dose  
 
:  
Adults 
 
 
: Refer to product’s leaflet as follow : no occlusive dress should 
be employed. Apply gel to the affected area three times daily leaving no residual material 
on the skin. 1 gram of gel applied to the affected area. 
The affected area are :  
o In the arms: hand, wrist, elbow, shoulder sinistra or dextra 
o In the legs: feet, ankle, knee sinistra or dextra 
o Upper back or Lower back 
3 times daily means : 
o application one time in morning (06.00 – 11.00),  

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o one time in afternoon (11.01 – 17.00),  
o one time in evening (17.01 – 23.00). 
Aplication of gel will use dosing card that provided in this clinical study. 
• Method of administration:  external use only. 
• Every visit, participants will get 2 tubes and in total are 6 tubes for 6 + 1 days 
application.  
 
Justification: 
The dosage for use refers to the Pirofel® gel leaflet which has been approved by BPOM 
RI. 
 
 
Dosing Card 
 
 
 
6.9 Study Drugs Labelling  
A label is needed for the study drug used.  
Investigational products will be given to Participants in tube only, no individual box.  
All Investigational Products tubes will be covered by white sticker, leaving only the tip of the 
tube containing the batch number and expiration date information. On top of the white sticker 
will be a study drug label that have specific code and number. 
Below is the labelling process for investigational products : 
The packaging label from investigational products will be covered by a white 
secured sticker. Only the bottom side (tail) which contains the batch number 
information is left open. 
 
Clinical study label will be put on the top of white sticker. 
 
 
 
Final label on the tube 

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Every tube will be numbered with drug number sequentially, as detailed: 
Test 
drug 
(Yellow 
sticker) 
Comparator drug (Orange 
Sticker) 
Comparator drug (Brown 
Sticker) 
C001 
H001 
P001 
C002 
H002 
P002 
C003 
H003 
P003 
etc. until the last of stock etc. until the last of stock 
etc. until the last of stock 
- 
Initial “C” for study drug and 3 digits number 
- 
Initial “H” for comparator drug and 3 digits number 
- 
Initial “P” for comparator drug and 3 digits number 
 
6.10 
Rescue Medication  
Rescue medication can be given to patient who have given informed consent. The rescue 
medication given is only if the subject can not bear the pain and to help reduce pain and per 
investigator advise. The rescue medication is a drug specifically provided for this study. The 
use of rescue medication will be recorded. The dosage of rescue medication will be determined 
by the Investigator.  
• Active Ingredients 
: Paracetamol 600 mg 
• Brand name 
 
: Sumagesic 
• Dose  
 
: 1 tablets maximum 3 dose per 24 hours or refer to Investigator 
advise. 
• 
Method of administration: Oral. 
 
6.11 
Storage Method 
Please keep under 30° C, protect and avoid direct light. Kept until 1 month after the product 
opens. 
 
6.12 
Dispensing, Storage, Management, and Collection Procedures 
The Study Drug Handling Manual will be provided and completed to ensure the study drugs 
are prepared, shipped, stored, dispensed, and returned to comply with regulations.  
 
The Investigational Products will be relabelled in Sponsor Technical Operations Plant Site. 
After the Sponsor ensures the quality of the product, the study drug will be relabeled, which 
means that this drug is used explicitly for clinical studies.  
The sponsor will deliver the study drug from the Technical Operations plant to each research 
site by courier, where it can monitor the temperature of the study drug delivery below 30°C. 
The Study Coordinator from each research site will ensure the storage of study drugs.  
During the study, the distribution of study drug participants will be prescribed by the 
Investigator based on randomization and dispensed to the participants by the Sports Therapist 
during the recovery program. 

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Use GraphPad QuickCalcs (https://www.graphpad.com/quickcalcs/randomize1/) to generate a 
random allocation list, ensuring equal numbers for each treatment group: 
• 
Group A: Piroxicam + Counterirritant 
• 
Group B: Piroxicam 
• 
Group C: Diclofenac 
Each eligible participant will be assigned a unique subject ID upon enrollment. The study 
coordinator will match the subject ID to a treatment group based on the pre-generated list. All 
tubes will be labeled with a sticker displaying only the randomization code to maintain blinding 
of both participants and investigators. The tube will then be dispensed to the participant 
according to the assigned code. Only the investigator will have access to the full randomization 
list. 
At the end of the study period, all study drugs will be returned by the participants to each site. 
This return process will be assisted by each Study Coordinator.  An then be sent to Technical 
Operations for destruction. 
 
6.13 
Adherence of study drug 
The dose of study drugs used during treatment period is checked based on the diary. If AE is 
occurred to the subject, Investigator can reduce or stop the dose of study drugs.  
 
6.14 
Unacceptable Concomitant Medication 
As explained in the clinical data and pharmacokinetics and pharmacodynamics of Paracetamol, 
the drugs mentioned below are known to have interactions with Paracetamol. For this reason, 
it is not acceptable to get the following treatment: 
o Opioid Analgesics 
o Oral Non Steroid Anti Inflammation Drugs 
Caution is recommended when analgesic products are used in combination because of 
possible increases in adverse events (e.g. nephrotoxicity, gastrointestinal lesions, 
bleeding). 
o Alcohol 
o Anticoagulants – Oral, Injection: Piroxicam is highly protein bound.  There is therefore 
a possibility of interaction with such drugs as coumarin anticoagulants  
 
 
7 STUDY PLAN 
 
7.7.1 Group Composition 
The following 2 groups are examined. The participants are allocated to these groups at the ratio 
of 1:1 that will be randomized. 
• Test drug group 
 
: Piroxicam plus Counterirritant Gel  
• Comparator group 
: Diclofenac diethylamine Gel 
• Comparator group 
: Piroxicam Gel 
 
7.7.2 Study period and process   
The study period for each participant is defined as “the period from the day of consent to the 
end of study (the day on which final tests and observation are finished or the day of 
discontinuation of the study). 

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 The participants considered as a complete visit after the 3rd visit examination on 6 + 1 days 
visit.  
- 
1st visit consider as Day 0  
- 
2nd visit is on Day 3 + 1 days 
- 
3rd visit is on Day 6 + 1 days 
 
 
 
 
The study’s flow in Day 0 : 
1) The registration officers will receive participants who register at the Eminence clinic 
and ask about symptoms related to the participant's visit. If the Participant complains 
of pain, the patient will be asked to fill out a registration form.  
2) The Principal Investigator or Sub Investigator will ask some questions (anamnesis) 
about the symptoms and explain about a clinical study that is conducted in the clinic. 
The PI or Sub-I will ask the Participant's willingness to join the research and explain 
regarding informed consent. If the Participant agrees, an informed consent will be 
signed. 
3) The participants are asked to complete the Individual Assessement of Pain.  
a. Form 2  
: Pemeriksaan Inventerisasi Rasa Nyeri Singkat 
4) The examination was carried out by conducting anamnesis, physical examination to 
confirmation the musculoskletal pain, range of motion and muscle test and confirmation 
related to the inclusion and exclusion criteria. If needed a radiologic examination will 
be conducted.  
5) In the examination, the PI or Sub-I should complete some Forms : 
a. Form 3  
: Pemeriksaan Awal Rasa Nyeri 
b. Form 4 : Pemeriksaan Indikator Rasa Nyeri Non Verbal 
c. Form 5 : Pemeriksaan Rentang Gerak 
d. Form 6 : Pemeriksaan Kekuatan Otot 
6) The PI or Sub-I will provide a diagnosis and therapy appropriate to the diagnosis. 

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7) Randomization of participants is carried out helped by Study Coordinator. The 
administration of therapeutic drugs according to the randomization list by a 
physiotherapist. The physiotherapist will provide information related to how to apply 
topical drugs to participants and provide the first dose of the investigational product in 
the therapy room. 
a. Form 7 : Pemberian aplikasi obat topikal by Physiotherapist 
b. Form 8 : Sensasi Termal by Participant 
8) Each participant will get physical therapy program refered to standard protocol and 
diagnosis 
9) Each participant will be given a pouch containing 2 tubes of investigational products, 
3 dosing cards,  4 strips of rescue medications, a participant diary, a study coordinator 
business card and a PI or Sub-I business card. 
 
 
The study’s flow in Day 1 -  Day 3 (+ 1 day) 
1) Participants will continue topical medication sessions at home. The Study Coordinator 
will assist with daily reminders for topical medication administration and diary 
completion. Participants will be asked to return to the study site on day 4 + 1 day with 
carrying the left over tubes and rescue medications, dosing cards,  diary and put inside 
the pouch.  
2) The participant will do the re-registration to registration officer and send back the pouch  
that will be given to the Fisiotherapist.  
3) The examinations will remains same as Day 0 from poin 2 until 5.  
4) The physiotherapist will provide information related to how to apply topical drugs to 
participants and applied the dose of the investigational product in the therapy room. 
5) The administration of therapeutic drugs according to the randomization list by a 
physiotherapist. The physiotherapist will provide information related to how to apply 
topical drugs to participants and provide the  dose of the investigational product in the 
therapy room. 
o Form 7 : Pemberian aplikasi obat topikal by Physiotherapist 

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o Form 8 : Sensasi Termal by Participant 
6) Each participant will be given a pouch containing 2 tubes of investigational products, 
3 dosing cards,  4 strips of rescue medications, a participant diary, a study coordinator 
business card and a PI or Sub-I business card. 
7) Participants will continue topical medication sessions at home. The Study Coordinator 
will assist with daily reminders for topical medication administration and diary 
completion. Participants will be asked to return to the study site on day 8 + 1 with 
carrying the left over tubes and rescue medications, dosing cards,  diary and put inside 
the pouch.  
The study’s flow in Day 5 -  Day 6 (+ 1 day) 
1) Participants will continue topical medication sessions at home. The Study Coordinator 
will assist with daily reminders for topical medication administration and diary 
completion. Participants will be asked to return to the study site on day 6 + 1 day with 
carrying the left over tubes and rescue medications, dosing cards,  diary and put inside 
the pouch.  
2) The participant will do the re-registration to registration officer and send back the pouch  
that will be given to the Fisiotherapist.  
3) The examinations will remains same as Day 0 from poin 2 until 5.  
4) The PI or Sub-I will give information that this is the last day of the study and the 
investigational drugs application last dose will be given by the physiotherapist.  
5) The administration of therapeutic drugs according to the randomization list by a 
physiotherapist. The physiotherapist will provide information related to how to apply 
topical drugs to participants and provide the last dose of the investigational product in 
the therapy room. 
o Form 7 : Pemberian aplikasi obat topikal by Physiotherapist 
o Form 8 : Sensasi Termal by Participan 
6) End of Study.  
 
 
7.7.3 Ensuring Safety of Participants 
Basic Points 
1) The Principal Investigator is responsible for all the medical decisions related to the 
study. 
2) The Principal Investigator ensures that sufficient medical care for all the AEs related to 
the study is provided to participants during their participation in the study and after that. 
3) The sponsor is responsible for continuously assessing the safety of study drugs. 
4) The sponsor promptly notifies all Principal Investigators involved in the study of the 
information that may adversely affect the safety of participants, influence the conduct 
of the study, or require changes in the approval of the continuation of the study by the 
institutional review board (IRB)/EC. 
7.8 CRITERIA AND PROCEDURE FOR DISCONTINUATION FOR PARTICIPANTS  
7.8.1 Discontinuation Criteria 
Investigator discontinues the study when a subject meets the following criteria. 
1. When continuation of the study is difficult due to worsening of the target disease of this 
study or symptoms caused by the target disease 
2. When a significant or persisting noncompliance with the protocol that makes it difficult 
to ensure safety or influences efficacy assessment was detected 

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3. When a subject is found not to meet the inclusion criteria for participants of this study 
or to meet the exclusion criteria 
4. When it is difficult to continue the study or a subject requests for discontinuation due 
to onset of AEs 
5. When a subject requests for discontinuation (not in relation to AEs) 
6. When a subject stops visiting the site, making it difficult to continue the study 
7. Other cases in which Investigator considers it difficult to continue the study 
 
7.8.2 Discontinuation Procedures 
When any event corresponding to “Discontinuation Criteria” occurs during the study treatment, 
Investigator discontinues the administration of study drugs, performs the observation and tests 
specified in “ Schedule and Efficacy and Safety Endpoints,” and enter the results, 
discontinuation day, and reason for discontinuation in case report form. 
Appropriate treatment including alternative therapies is provided after discontinuation. 
When the study is discontinued due to occurrence of a safety problem in the subject concerned, 
appropriate measures are taken and the problem is addressed in accordance with “ Ensuring 
Safety of Participants.” 
When a subject stops visiting the site, Investigator asks a subject to visit the site and efforts are 
made to perform the observation and tests specified in “Schedule, Efficacy and Safety 
Endpoints.” 
If the designated observation and tests cannot be performed, Investigator promptly conducts 
follow-up investigation on the course after the latest observation and AEs over the phone, by 
letter, or other possible methods and enters the result in case report form. When confirmation 
was made with a person other than the subject for a compelling reason, the reason and the 
relationship of this person with the subject are entered in case report form. 
 
7.9 STUDY, EFFICACY AND SAFETY ENDPOINTS SCHEDULE 
 
7.9.1 Primary Endpoint 
The assessment of primary endpoint wil be assessed through form 2, Inventerisasi Rasa Nyeri 
Singkat on 1st Visit, 2nd Visit and 3rd Visit.  
The primary end-point is the difference BPI scale >  3 , from initial scale of pain to the end of 
treatment will be captured as the primary efficacy endpoint. 
 
7.9.2 Secondary Endpoint 
The assessment of secondary endpoints will be assessed through : 
1st Visit
2nd Visit
3rd Visit
Data Input & Locked
Days
Day 0 
Day 1 - Day 2
Day 3 + 1 day
Day 4 - Day 5
Day 6 + 1 day
Day 7 - Day 15
Informed consent
X
PI, Subject
Inclusion and Exclusion 
Criteria 
X
PI, Sub I
Medical Examination
X
X
X
PI, Sub I
Randomization
X
Study Coordinator
Dispense Study Drugs
X
PI, Sub I, Study Coordinator , 
Physiotherapist
Recovery Treatment :
- Aplication of Study 
Drugs to affected site
- Physiotherapy and 
exercise based on 
diagnosis and treatment 
from PI, Sub-I
X
X
X
PI, Sub PI, Study Coordinator, 
Physiotherapist
Primary and Secondary 
endpoint assessement
X
X
X
PI, Sub-I, Physiotherapist
Application of Study 
Drugs at home
X
X
Subject
Subject's diary
X
X
X
X
X
Subject
Concomitant medication
X
X
X
X
X
PI, Sub PI, Subject
Rescue medication
X
X
X
X
X
PI, Sub PI, Subject
Adverse events 
X
X
X
X
X
PI, Sub PI, Subject
Study drugs and Diary 
returned
X
Registration officer, 
Physiotherapist
Data input 
X
X
X
X
Study Coordinator
Data locked
X
Study Coordinator 
Monitoring
X
X
X
CRA
Note

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- 
Form 3 
: Pemeriksaan nyeri awal pasien  
- 
Form 4  
: Pemeriksan indikator rasa nyeri non verbal 
- 
Form 5  
: Pemeriksaan rentang gerak 
- 
Form 6 
: Pemeriksaan kekuatan otot 
By Principal Investigator or Sub Investigator on 1st Visit, 2nd Visit and 3rd Visit.  
 
- 
Form 8 
: thermal sensation, thermal comfort, and thermal acceptance and time 
of thermal sensation. 
By Participant on 1st Visit, 2nd Visit and 3rd Visit. 
 
- 
Adverse events symptoms, concomitant medication, rescue medication that will be 
described in the Diary Participant.  
By Participant on Day 0 until study is completed.  
 
 
 
7.10 
STATISTICAL ANALYSIS 
 
7.4.1 Analysis Sets 
In the efficacy analysis, the Per Protocol Set (PPS) will be used as the primary analysis set, 
while the Full Analysis Set (FAS) will serve as the secondary analysis set. For safety analysis, 
the Safety Analysis Set will be used. The definitions are as follows: 
• 
Per Protocol Set (PPS): 
The PPS includes participants who do not have any major protocol violations (such as 
not meeting inclusion/exclusion criteria or poor compliance), and who have 
completed the required assessments of the primary endpoint as specified in the 
protocol. 
• 
Full Analysis Set (FAS): 
The FAS includes all participants who received at least one dose of the study drug and 
had at least one post-baseline assessment for efficacy endpoints. This set reflects the 
intention-to-treat principle. 
• 
Safety Analysis Set: 
The Safety Analysis Set includes all participants who received at least one dose of the 
study drug and had at least one post-baseline safety assessment. All safety data, 
including adverse events and rescue medication use, will be analyzed in this set. 
7.4.2 Statistical Analysis Plan  
The statistical analysis will be performed after data finalization and database lock, following 
the predefined analysis sets (PPS, FAS, and Safety Analysis Set). All analyses will be 
conducted using standard statistical software (e.g., SPSS, SAS, or R), with the level of 
statistical significance set at p < 0.05, unless otherwise adjusted. 
Efficacy Analysis 
• 
Primary Endpoint (Pain Score using Brief Pain Inventory): 
o Test: Analysis of Covariance (ANCOVA) adjusting for baseline BPI score 

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o Equivalence testing: Pairwise comparisons using two one-sided t-tests 
(TOST) to assess whether the difference in mean change from baseline falls 
within the equivalence margin (±1.0) 
o Assumptions: Normality and homogeneity of variance will be checked. If 
violated, non-parametric equivalent (e.g., Wilcoxon rank-sum test) will be 
used. 
• 
Secondary Endpoints: 
o Range of Motion (ROM) and Muscle Strength: 
▪ 
Test: Repeated 
Measures 
ANOVA or mixed-effects 
model, 
depending on data completeness and correlation structure 
▪ 
If non-normal: Friedman test or Wilcoxon signed-rank test for 
within-group, Kruskal-Wallis test for between-group comparisons. 
o Thermal Sensation, Comfort, and Acceptance (ASHRAE Scale): 
▪ 
Test: Chi-square 
test or Fisher’s 
exact 
test for 
categorical 
comparisons 
▪ 
Ordinal regression may be used to explore patterns of thermal 
perception across groups. 
o Responding Analysis (pain reduction ≥3 points): 
▪ 
Test: Chi-square test for group-wise comparison of response rates 
▪ 
Risk difference and number needed to treat (NNT) will be calculated. 
Safety Analysis 
• 
Adverse Events (AEs) and Adverse Drug Reactions (ADRs): 
o Test: Chi-square test or Fisher’s exact test for comparing incidence across 
groups 
o Descriptive statistics for type, severity, onset, and duration 
o Severity grading and causality assessment using Naranjo’s algorithm. 
• 
Rescue Medication Use: 
o Test: Poisson regression or negative binomial regression if data are 
overdispersed 
o Summarized as a mean number of doses used per participant and compared 
between groups. 
Demographic and Baseline Characteristics 
• 
Continuous Variables (e.g., age, BMI): 
o Test: One-way ANOVA or Kruskal-Wallis test (if non-normal distribution) 
• 
Categorical Variables (e.g., sex, diagnosis): 
o Test: Chi-square test or Fisher’s exact test as appropriate 
 
Missing Data Handling 
• 
Primary Analysis will be based on the Per Protocol Set, with sensitivity analysis 
using Full Analysis Set (FAS)under intention-to-treat (ITT) principles. 
• 
Multiple imputation will be considered for missing primary endpoint data if the 
proportion of missing data exceeds 5%. 
 
 
7.11 
COMPLIANCE WITH AND DEVIATION FROM PROTOCOL OR CHANGES 
AND REVISION OF PROTOCOL  

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7.11.1 Compliance with and Deviation from or Changes in Protocol 
Investigator must not deviate from or change the protocol unless the Principal Investigator 
obtains prior written agreement with the sponsor and written approval by the institutional 
review board (IRB)/EC. However, this does not apply when the deviation or change is 
medically inevitable, for example, deviation or change for avoiding urgent risk to participants, 
or when the change does not affect the conduct of the study (for example, change in phone 
numbers). 
1) Investigator can deviate from or change the protocol without prior written agreement 
with the sponsor and prior approval by the institutional review board (IRB)/EC for 
medically compelling reasons, for example, to avoid urgent risk to participants. In such 
cases, the Principal Investigator notifies the sponsor of the details of the deviation or 
change and its reason. The Principal Investigator also discusses the revision of the 
protocol with the sponsor and reaches an agreement. The approval of draft revision by 
the institutional review board (IRB)/EC is obtained as soon as possible. 
2) The Principal Investigator promptly submits the report of all the changes in the study 
that significantly affect the conduct of the study or increase the risk to participants to 
the sponsor and the institutional review board (IRB)/EC. 
3) Investigator records all the actions that deviate from the protocol. Among the actions 
deviate from the protocol, the Principal Investigator prepares the documents that 
include the reasons, immediately submits them to the sponsor, and retains a copy only 
for the actions for medically compelling reasons including avoidance of urgent risk to 
participants. 
 
7.11.2 Revision of Protocol 
The protocol and case report form are revised by the following procedures. 
1) When the sponsor considers the revision necessary, the sponsor provides the Principal 
Investigator the draft revision of the protocol and case report form and other necessary 
materials and information. 
2) The sponsor gives the Principal Investigator time necessary for him or her to 
sufficiently review the materials and information including the draft revision of the 
protocol provided in accordance with the previous clause and discuss with the sponsor. 
3) After discussing with the Principal Investigator, the sponsor reaches an agreement with 
the Principal Investigator on the details of the revised protocol and case report form and 
compliance with the revised protocol. The sponsor and the Principal Investigator each 
sign, and date the written agreement to prove the above agreement. Similar processes 
are followed when the protocol and case report form are corrected at the direction of 
the institutional review board (IRB)/EC, within the range accepted by the sponsor. 
4) The sponsor promptly submits the revised protocol and case report form and promptly 
obtains the approval by the institutional review board (IRB)/EC. For changes in the 
protocol related to administrative matters (for example, changes in monitors or changes 
in phone numbers, etc.), addition or deletion of other study sites, and changes in the 
Principal Investigator or other personnel at other study sites, the sponsor notifies the 
Principal Investigator of the details of the changes. 
 
 
7.11.3 Completion or Discontinuation and Interruption of Study 
 
7.11.3.1 
Completion of Study 

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The completion day of the study for each subject is defined as “the day on which observation 
of all items specified in the protocol is completed or discontinuation day for the subject” and 
the completion day of the study for each study site as “the latest day among the study 
completion days for the participants enrolled at the study site concerned.” 
 
 
After:  the study treatment and observation specified in the protocol were 
completed for the last subject at the study site concerned, the Principal Investigator promptly 
notifies the institutional review board (IRB)/EC and the sponsor of the completion of the study 
in writing and reports the outline of the study results based on the report he or she prepared to 
the institutional review board (IRB)/EC and the sponsor. 
 
 
7.11.3.2 
Discontinuation or Interruption of Entire Study 
Criteria for Discontinuation or Interruption of Entire Study 
The sponsor promptly discusses the discontinuation or interruption of the study with the 
medical expert when the following criteria are met and continuation of the study at all the study 
sites is considered difficult or meaningless. 
1) When “unexpected” serious AEs (diseases, disorders, deaths) occur 
2) When information indicating that the tendencies in occurrence of “expected” 
significant AEs including number of incidents, frequency, and conditions for 
occurrence cannot be predicted based on the investigator’s brochure was obtained 
3) When information indicating that the tendencies in occurrence of ADRs including 
number of incidents, frequency, and conditions for occurrence markedly changed 
for the worse was obtained 
4) When information indicating or not indicating the superiority of the test drug to the 
comparator was obtained 
5) When other information affecting the continuation of the study was obtained 
a. Procedures for Discontinuation or Interruption of Entire Study 
b. The entire study is discontinued or interrupted by the following procedures. 
6) When the entire study is discontinued or interrupted, the sponsor promptly notifies 
all the Principal Investigators involved in the study and the regulatory agency to 
that effect and the detailed reasons in writing. 
7) When the sponsor decides the discontinuation or interruption of the entire study and 
notifies Principal Investigators of the decision, Principal Investigators promptly 
notifies the institutional review boards (IRB)/EC to that effect in writing and 
explains the details of the discontinuation or interruption to the institutional review 
board (IRB)/EC. 
8) When the Principal Investigators are notified of the discontinuation or interruption 
of the entire study, they promptly notify the participants receiving study treatment 
to that effect and take appropriate measures including switching to other therapies. 
 
 
7.11.4 Discontinuation or Interruption at Study Sites 
 
7.11.4.1 
Criteria for Discontinuation or Interruption at Study Sites 
When the following criteria are met, the sponsor assesses whether or not the study can be 
continued at all or part of the study sites. 
1) When the protocol needs to be changed and some study sites cannot respond to the 
change 
2) When the sponsor cannot approve an instruction for correction based on the opinion 
of the institutional review board (IRB)/EC 

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3) When the institutional review board (IRB)/EC instructed to discontinue the study  
4) When some study sites violated GCP, the protocol, or study contract significantly 
or continuously 
 
7.11.4.2 
Procedures for Discontinuation or Interruption at Study Sites 
The study is discontinued or interrupted at study sites by the following procedures. 
1) When the Principal Investigator discontinued or interrupted the study, he or she 
promptly explains the discontinuation or interruption in detail in writing to the 
sponsor and the institutional review board (IRB)/EC. 
2) When the institutional review board (IRB)/EC decided discontinuation or 
interruption of the study and notifies to that effect, the Principal Investigator 
promptly notifies the sponsor. 
 
 
7.12 
DIRECT ACCESS TO SOURCE DOCUMENTATION  
 
7.12.1 Direct Access to Source Documents, etc. 
The Principal Investigator accepts the monitoring and audit by the sponsor and inspection by 
the institutional review board (IRB)/EC and the regulatory agency and provides all the study-
related records including source documents for direct access. 
 
7.12.2 Method of Direct Access 
If necessary, the study site and sponsor can have access to clinical study documents. The 
justification for opening access to clinical study documents will be discussed by the study site 
and the sponsor. Any access to clinical study documents requires prior Sponsor approval. 
 
7.13 
QUALITY CONTROL AND QUALITY ASSURANCE OF STUDY  
The sponsor responsibly performs the quality assurance based on the standard operating 
procedures and maintains quality control system in order to assure that the study is conducted 
and data are generated, recorded, and reported in compliance with the protocol, the 
pharmaceutical affairs law, and GCP. 
The sponsor will ensure that the reporting of adverse events  that occur in this study will be 
reported to the the institutional review board (IRB)/EC and also BPOM RI in accordance with 
regulations applied in Indonesia. 
 
7.13.1 Quality Control of Study 
The sponsor applies quality control at each step of the handling of data in order to assure the 
reliability of all the study-related data and their appropriate processing. 
The monitors assigned by the sponsor perform monitoring (including direct access to the study-
related record such as source documents) according to the standard operating procedures and 
confirm that the study is being conducted appropriately at study sites in compliance with the 
protocol, the standard operating procedures, and Good Clinical Practice. 
 
7.13.2 Quality Assurance of Study 
The sponsor assures the quality of the study by establishing an audit department that is 
independent of the department that implements the study. In order to assure the quality of the 
study, the personnel in charge of audit performs audit at appropriate timing at the sponsor as 
well as at study sites and other facilities involved in the study as necessary, in accordance with 
the standard operating procedures of the sponsor. 
 

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7.14 
ETHICAL IMPLEMENTATION OF STUDY  
 
7.14.1 Review of Study 
This study is reviewed by the institutional review board (IRB)/EC selected by each study site 
as to whether or not its implementation is appropriate from the perspective of ethical, scientific, 
and medical adequacy. 
 
7.14.2 Continued Review of Study 
The adequacy of continued implementation of this study at a particular study site is reviewed 
once a year or more frequently, or in the following cases. 
1) When the sponsor notified the Principal Investigator of serious and unexpected ADRs 
or other events 
2) When the Principal Investigator reported serious AEs or other events 
3) When the Principal Investigator reported a revision of consent form and other written 
information for patients 
4) When the Principal Investigator submitted the overview of the current status of the 
study for the review regarding continuation of the study 
5) Other cases in which the Principal Investigator considers that the review regarding 
continuation of the study is necessary 
The Principal Investigator requests the opinion of the institutional review board (IRB)/EC 
regarding the adequacy of continuation of the study at the study site concerned. 
 
7.14.3 Matters Related to Protection of Privacy and Personal Information of Participants 
In order to protect the privacy and personal information of participants, participants are 
identified by subject IDs. 
In the preparation and handling of case report forms and the monitoring, audit, and other tasks 
performed by the sponsor, as well as when the study results are published, attention is paid to 
protection of privacy and personal information of participants. 
 
 
7.15 
STORAGE OF RECORD  
 
7.15.1 Investigator 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements or by an agreement with the sponsor. 
 
 
 
 
7.15.2 Institutional Review Board (IRB)/EC 
The institutional review board (IRB) /EC is an independent body constituted of medical, 
scientific and non- scientific member, whose responsibility is to ensure safeguard the rights, 
safety, and well-being of all trial participants. 
The 
institutional review board (IRB) /EC should retain all relevant records (e.g., written 
procedures, membership lists, lists of occupations/affiliations of members, submitted 
documents, minutes of meetings, and correspondence) for a period of at least 3 years after 

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completion of the trial and make them available upon request from the regulatory 
authority(ies). 
7.15.3 Sponsor 
1) The sponsor specific essential documents should be retained until at least 2 years after the 
last approval of a marketing application in an ICH region and until there are no pending 
or contemplated marketing applications in an ICH region or at least 2 years have elapsed 
since the formal discontinuation of clinical development of the investigational product. 
These documents should be retained for a longer period however if required by the 
applicable regulatory requirement(s) or if needed by the sponsor. 
2) When the storage of the documents that should be stored by the Principal Investigator or 
the institutional review board (IRB) /EC becomes unnecessary, the sponsor notifies the 
institutional review board (IRB) /EC to that effect through Investigator. 
 
 
7.16 
MONETARY PAYMENT 
The sponsor pays the cost of this study based on the contract with each study site. 
 
 
7.17 
INSURANCE 
The sponsor takes necessary measures including issued guarantee letter in order to compensate 
for the treatment of health hazards of participants caused by the study and other losses. 
 
7.18 
COMPENSATION FOR HEALTH HAZARDS 
1) When any health hazard occurs to a subject in this study, the study site and the sponsor 
respond to it for the subject or his or her bereaved family in the following manner. 
2) The study site makes all possible efforts to treat the health hazard. 
3) If neither intention nor negligence of the sponsor was involved and no other parties 
have liability for the health hazard caused by the study, the sponsor provides 
compensation based on its compensation system. However, if the health hazard was 
proven to be the results of the subject’s own intention or significant negligence, the 
compensation is reduced or not provided. If a health hazard that newly occurred is 
causally unrelated to the study, it is not compensated. 
4) If intention or negligence of the sponsor, the study site, a party commissioned by the 
sponsor or the study site to carry out study-related tasks, or other parties was involved 
in the health hazard caused by the study, the party that is legally responsible for this 
health hazard provides the compensation. 
5) Adverse event that happened during observation and treatment period will be monitored 
by investigator and sponsor. The cost for theadverse event related to the study will be 
compensated by sponsor. 
 
7.19 
HANDLING OF PUBLICATION  
The sponsor is free to use the information obtained in this study for the purposes including the 
application for marketing approval related to the test drug. 
References: 
1. J.B. Fourtillan and J. Girault. Piroxicam Plasma Concentrations Following 
Repeated 
Topical Application of a Piroxicam 0.5% Gel. Drug Invest. 4 (5): 435-440, 
1992. 

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2. Internal Data Study. Counterpain PXM.  Bristoll Myers Squibb. Thailand. 
1990. 
3. Derry_S, Moore_RA, Gaskell_H, McIntyre_M, Wi_en_PJ. Topical NSAIDs 
for acute musculoskeletal pain in adults. Cochrane Database of Systematic 
Reviews 2015, Issue 6. Art. No.: CD007402. 
4. Mcmahon, Stephen B. Et al. The burden of musculoskeletal pain and the role 
of topical non-steroidal anti-inflammatory drugs (NSAIDs) in its treatment. 
Ten underpinning statements from a global pain faculty. Curr Med Res 
Opin. 2021 Feb;37(2):287-292 
5. Yudiyanta, Et al. Assessment Nyeri. CDK-226/ vol. 42 no. 3, th. 2015. 
6. Pedoman Monitoring Efek Samping Obat bagi Tenaga Kesehatan. BPOM RI. 
2012. 
7. Mizner RL, Petterson SC, Snyder-Mackler L. Quadriceps strength and the 
time course of functional recovery after total knee arthroplasty. J Orthop 
Sports Phys Ther. 2005 Sep;35(9):559-65. doi:10.2519/jospt.2005.35.9.559. 
8. Cleland JA, Mintken PE, Talbert J, et al. Manual physical therapy and 
exercise versus supervised home exercise in the management of patients with 
inversion ankle sprain: a multicenter randomized clinical trial. J Orthop 
Sports Phys Ther. 2013;43(7):443–455. doi:10.2519/jospt.2013.4514 
9. Picha KJ, Harding JL, George SZ. Clinically important differences in range 
of motion and strength for patients with musculoskeletal disorders of the 
upper 
extremity. 
J 
Hand 
Ther. 
2020;33(3):403–412. 
doi:10.1016/j.jht.2020.01.007 
10. Stratford P, Binkley J, Solomon P, et al. Assessing change over time in 
patients with low back pain. Phys Ther. 1994 Jun;74(6):528-33. 
11. Schweiker, M. Et al.  Evaluating assumptions of scales for subjective 
assessment of thermal environments –Do laypersons perceive them the way, 
we researchers believe?. Energy & Buildings 211 (2020) 109761. 
12. Kocak, AO. Et al. Comparison of topical capsaicin and topical piroxicam in 
the treatment of acute trauma-induced pain: A randomized double-blind trial. 
The American Journal of Emergency Medicine Volume 38, Issue 
9, September 2020, Pages 1767-177. 
13. Leaflet Counterpain PXM. Indonesia 
14. Leaflet Hotin DCL. Indonesia 
15. Leaflet Pirofel. Indonesia 
 
 
 
 
 
 
 
 
 
 
Appendix 1  
FORMULIR PEMERIKSAAN 

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Jenis Formulir 
Diisi oleh 
Formulir 2, Inventerisasi Rasa Nyeri Singkat 
 
Pasien 
Formulir 3, Pemeriksaan Awal Nyeri Pasien 
Dokter Pemeriksa 
 
Formulir 4, Pemeriksaan Indikator Rasa 
Nyeri Non – Verbal 
 
Dokter Pemeriksa 
Formulir 5,  Pemeriksaan Rentang Gerak 
 
Dokter Pemeriksa 
 
Formulir 6, Pemeriksaan Kekuatan Otot 
Dokter Pemeriksa 
 
Formulir 7, Pemberian aplikasi obat topikal 
Fisioterapis 
 
Formulir 8, Sensasi Termal 
 
Pasien 
Formulir 9, Program Fisioterapi & Latihan 
Fisioterapis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FORMULIR PASIEN 
FORMULIR PEMERIKSAAN 2 

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INVENTERISASI RASA NYERI SINGKAT 
Nama 
:  
 
Tanggal  
:  
 
Waktu 
:  
 
Kunjungan ke 
:  
 
Isilah pertanyaan dibawah ini sesuai dengan kondisi yang Anda rasakan hari ini. 
Lingkari yang paling mendekati kondisi Anda. 
1 Sepanjang hidup kita, kebanyakan dari kita mengalami 
rasa sakit dari waktu ke waktu (seperti sakit kepala 
ringan, terkilir, dan sakit gigi).  
 
Pernahkah Anda merasakan sakit selain rasa sakit biasa 
tersebut hari ini? 
 
 
 
: 
 
 
 
 
Ya 
 
Tidak 
 
2 Pada diagram, arsir area di mana Anda merasakan sakit. Beri tanda X pada area yang 
sangat sakit 
 

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3 Nilai rasa sakit Anda dengan melingkari salah satu angka yang sangat menggambarkan 
rasa sakit Anda yang TERBURUK di 24 jam terakhir. 
 
 
4 Nilai rasa sakit Anda dengan melingkari salah satu angka yang sangat menggambarkan 
rasa sakit Anda yang PALING RINGAN di 24 jam terakhir 
 
 
 

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5 Nilai rasa sakit Anda dengan melingkari salah satu angka yang sangat menggambarkan 
rasa sakit Anda RATA-RATA. 
 
 
6 Nilai rasa sakit Anda dengan melingkari salah satu angka yang menggambarkan rasa 
sakit yang sedang Anda rasakan SEKARANG. 
 
 
7 Pengobatan atau perawatan apa yang Anda terima 
untuk rasa sakit Anda? 
: 
 
 
 
8 Dalam 24 jam terakhir, seberapa banyak rasa sakit tersebut berkurang setelah menerima 
pengobatan atau perawatan? Lingkari salah satu persentase yang sangat menggambarkan 
RASA LEGA yang Anda rasakan. 
 
 
9 Lingkari salah satu angka yang menggambarkan bagaimana, selama 24 jam terakhir, rasa 
sakit menganggu Anda dalam : 

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A. Kegiatan sehari-hari: 
 
 
 
B. Suasana hati: 
 
 
 
C. Kemampuan berjalan: 
 
 
 
D. Pekerjaan biasa (termasuk bekerja di luar rumah dan pekerjaan rumah): 
 
 
 
E. Hubungan dengan orang lain: 
 
 

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F. Tidur: 
 
 
 
G. Kesenangan hidup: 
 
 
 
 
 
Paraf Pasien: _____________  Tanggal : _________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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FORMULIR DOKTER PEMERIKSA 
 
FORMULIR PEMERIKSAAN 3 
PEMERIKSAAN AWAL RASA NYERI  
Nama 
:  
Tanggal  
:  
Waktu 
:  
Kunjungan ke 
:  
 
1 
Lokasi rasa nyeri 
 
 
2 
Pemeriksaan intensitas dan karakter rasa nyeri 
1. Serangan dan pola sementara : 
• Kapan Anda mulai merasakan sakit?  
• Seberapa sering rasa sakit itu muncul? 
• Apakah ada perubahan dalam intensitasnya?  
 
2. Lokasi 
• Dimana Anda merasakan sakitnya?  
• Apakah dirasakan lebih dari satu titik?  
 
3.  Keterangan  
• Bagaimana rasa sakit yang Anda rasakan?  
• Bagaimana cara Anda menjelaskan rasa sakit tersebut?  
 
 

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4. Intensitas  
Dalam skala 0 hingga 10, dengan 0 berarti tidak sakit sama sekali dan 10 berarti rasa 
sakit terburuk yang dapat Anda bayangkan,  
• Berapa skalanya saat ini?  
• Berapa skalanya ketika Anda sedang merasa sangat kesakitan?  
• Berapa skalanya ketika Anda merasa sakitnya di saat terbaik?  
 
5. Faktor yang memperburuk dan meringankan –  
• Apa yang meringankan rasa nyeri Anda?  
• Apa yang memperburuk rasa nyeri Anda?  
 
6. Perawatan sebelumnya –  
• Jenis pengobatan apa yang pernah Anda lakukan untuk meringankan rasa 
nyeri Anda?  
• Apakah pengobatan itu efektif?  
 
7. Efek –  
• Bagaimana rasa nyeri tersebut mempengaruhi fungsi fisik dan sosial Anda? 
 
3 
Pemeriksaan psikososial 
 
 
 
 
 
 
4 
Pemeriksaan fisik dan neurologis 
 
 
 
 
 
Paraf Dokter Pemeriksa : ________________ Tanggal : __________________ 
 
 
 
 
 

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FORMULIR DOKTER PEMERIKSA 
 
FORMULIR PEMERIKSAAN 4 
PEMERIKSAAN INDIKATOR RASA NYERI NON- VERBAL  
Nama 
:  
Tanggal  
:  
Waktu 
:  
Kunjungan ke 
:  
Penilaian:  
• Beri nilai 0 jika perilakunya tidak teramati.  
• Beri nilai 1 jika perilaku muncul secara singkat selama beraktivitas atau sedang 
beristirahat.  
Jumlah angka indikasi dihitung untuk perilaku yang diamati : 
• saat sedang beristirahat,  
• dalam pergerakan, dan  
• keseluruhan.  
 
Tidak ada batas nilai yang jelas dalam mengindikasikan tingkat keparahan suatu rasa nyeri; 
sebaliknya, keberadaan perilaku apa pun dapat menjadi indikasi suatu rasa sakit, menjamin 
investigasi pengobatan, dan pengawasan lebih lanjut dari para praktisi 
No 
Perilaku 
Saat beraktivitas 
Saat beristirahat 
1 
Keluhan vocal: nonverbal (Menghela 
napas, 
terkesiap, 
erangan, 
menggeram, menangis) 
 
 
 
2 
Ekspresi 
Wajah/Meringis 
(Alis 
berkerut, mata menyipit, gigi terkatup 
rapat, 
bibir 
mengatup, 
mulut 
menganga, ekspresi terdistorsi) 
 
 
 
3 
Bersiap 
(Mencengkeram 
atau 
berpegangan pada mebel, perkakas, 
atau area yang terdampak selama 
bergerak) 
 
 
 
4 
Gelisah (Terus atau sesekali berganti 
posisi, berayun, tangan bergerak 
sesekali atau terus menerus, tidak 
bisa diam) 
 
 
 

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5 
Menggosok (Memijat bagian yang 
terdampak) 
 
 
 
6 
Keluhan 
vocal: 
verbal 
(Ucapan 
mengekspresikan ketidaknyamanan 
atau rasa sakit (misalnya; “aduh”, 
“sakit”); mengumpat saat bergerak; 
berseru 
atau 
protes 
[misalnya, 
“berhenti”, “cukup”] 
 
 
 
 
Nilai total 
 
 
 
 
 
 
Paraf Dokter Pemeriksa : ________________ Tanggal : __________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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FORMULIR DOKTER PEMERIKSA 
 
FORMULIR PEMERIKSAAN 5 
PEMERIKSAAN RENTANG GERAK 
Nama 
:  
Tanggal  
:  
Waktu 
:  
Kunjungan ke 
:  
 
S 
 
 
O 
 
 
 
 
 
 
 
 
 
A 
 
 
 
P 
 
 
 
 
 
Paraf Dokter Pemeriksa : ________________ Tanggal : __________________ 
 
 

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FORMULIR DOKTER PEMERIKSA 
 
FORMULIR PEMERIKSAAN 6 
PEMERIKSAAN KEKUATAN OTOT 
Nama 
:  
Tanggal  
:  
Waktu 
:  
Kunjungan ke 
:  
 
S 
 
 
O 
 
 
 
 
 
 
 
 
 
 
A 
 
 
 
P 
 
 
 
 
Paraf Dokter Pemeriksa : ________________ Tanggal : __________________ 
 
 

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FORMULIR FISIOTERAPIS 
 
PEMBERIAN OBAT TOPIKAL 
NOMOR OBAT TOPIKAL YANG DIBERIKAN :  
Nama 
:  
Tanggal  
:  
Waktu 
:  
Kunjungan ke 
:  
Lokasi area pengaplikasian obat topikal  
 
 
 
 
 
 
Sebelah Kiri / Kanan 
:  
 
 
 
Paraf Fisioterapis : _______________  Tanggal : ______________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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FORMULIR PASIEN 
 
FORMULIR PEMERIKSAAN 7 
PEMERIKSAAN SENSASI TERMAL (ASHRAE) 
Nama 
:  
 
Tanggal  
:  
 
Waktu 
:  
 
Kunjungan ke 
:  
 
 
Sensasi Termal 
Mohon lingkari skala berikut yang sesuai dengan yang Anda rasakan setelah diaplikasikan 
obat topikal 
 
 
Sensasi termal tersebut dirasakan dalam waktu :  
 
________________  Menit 
 
________________  Detik 
 
 
 
 

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Kenyamanan setelah aplikasi obat topikal 
Mohon lingkari skala berikut yang sesuai dengan yang Anda rasakan setelah diaplikasikan 
obat topikal 
 
 
 
 
 
Penerimaan sensasi termal yang diaplikasikan secara topikal 
Mohon lingkari skala berikut yang sesuai dengan yang Anda rasakan setelah diaplikasikan 
obat topikal 
 
 
 
 
 
 
Paraf Pasien : ______________  Tanggal : _________________ 
 
 
 
 
 
 

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FORMULIR FISIOTERAPIS 
 
PROGRAM FISIOTERAPI DAN LATIHAN 
Nama 
:  
 
Tanggal  
:  
 
Waktu 
:  
 
Kunjungan ke 
:  
 
Lokasi area nyeri 
 
 
Sebelah Kiri / Kanan 
:  
 
Program fisioterapi yang 
dilakukan 
:  
 
 
Program 
latihan 
yang 
dilakukan 
:  
 
 
 
 
Paraf Fisioterapis : _______________  Tanggal : ______________________ 
 
 

CONFIDENTIAL 
 
PROTOCOL: CT_CTPPXM001_PRT_V003/IX/2025 
 
Page 48 of 51 
 
                      
                         
Appendix 2 
PROGRAM FISIOTERAPI STANDAR UNTUK PARTISIPAN 
 
Diagnosis 
OSTEOARTRITIS 
Program Terapi & Latihan 
Waktu Pengerjaan (menit) 
Latihan Peregangan: 
Peregangan otot paha belakang, Peregangan 
otot betis, Peregangan otot paha depan 
 
Latihan Isometrik: 
Quadriceps isometris 
Tahan selama 15 detik, dilakukan sebanyak 
3 set 
 
 
 
Tahan selama 15 detik, dilakukan sebanyak 
3 set 
 
Terapi Manual: 
Pemijatan pada area otot yang kaku dan 
tegang 
Dilakukan oleh Fisioterapi selama 10-15 
menit 
Terapi modalitas: 
TENS (Transcutaneous Electrical Nerve 
Stimulation)  
 
Penggunaan Ultrasound 
 
Dilakukan selama 15 menit 
 
Dilakukan selama 10 menit 
Terapi tambahan jika pasien datang 
dalam keadaan bengkak: 
 
Terapi Es, kompres  
 
 
 
Dilakukan selama 15 menit 
 
 
Diagnosis 
ANKLE SPRAIN 
Program Terapi & Latihan 
Waktu Pengerjaan (menit) 
Latihan Rentang Gerak: 
Mobilisasi anteroposterior sendi talokrural 
 
Latihan isometris: 
Dorsofleksi, plantarfleksi, inversi dan eversi 
menggunakan tahanan 
 
10 repetisi, 3set 
 
 
Tahan 10 detik, 3set 

CONFIDENTIAL 
 
PROTOCOL: CT_CTPPXM001_PRT_V003/IX/2025 
 
Page 49 of 51 
 
                      
                         
Terapi Manual: 
Pemijatan pada area otot yang kaku dan 
tegang 
Dilakukan oleh Fisioterapi selama 10-15 
menit 
Terapi modalitas: 
TENS (Transcutaneous Electrical Nerve 
Stimulation)  
 
Penggunaan Ultrasound 
 
Dilakukan selama 15 menit 
 
Dilakukan selama 10 menit 
Terapi tambahan jika pasien datang 
dalam keadaan bengkak: 
 
Terapi Es, kompres  
Ankle Pumping 
 
 
 
Dilakukan selama 15 menit 
Dilakukan 10 repetisi, dilakukan sebanyak 
3set 
 
Diagnosis 
TENDINITIS PATELLA 
Program Terapi & Latihan 
Waktu Pengerjaan (menit) 
Latihan Fleksibilitas: 
Fleksibilitas fleksor pinggul dan paha depan 
Mobilitas lumbosacral 
 
Latihan Isometrik:  
Quadriceps isometric 
 
Latihan Penguatan: 
Side Lying abduction, clam shell, hipe hike 
satu kaki 
 
 
Dilakukan 3 set 15 repetisi 
 
 
 
Tahan 10 detik, dilakukan 3set 
 
Dilakukan 3 set 15 repetisi 
 
Terapi Manual: 
Pemijatan pada area otot yang kaku dan 
tegang 
Dilakukan oleh Fisioterapi selama 10-15 
menit 
Terapi modalitas: 
TENS (Transcutaneous Electrical Nerve 
Stimulation)  
 
Penggunaan Ultrasound 
 
Dilakukan selama 15 menit 
 
Dilakukan selama 10 menit 

CONFIDENTIAL 
 
PROTOCOL: CT_CTPPXM001_PRT_V003/IX/2025 
 
Page 50 of 51 
 
                      
                         
Terapi tambahan jika pasien datang 
dalam keadaan bengkak: 
 
Terapi Es, kompres  
 
 
 
Dilakukan selama 15 menit 
 
Diagnosis 
TENNIS ELBOW 
Program Terapi & Latihan 
Waktu Pengerjaan (menit) 
Latihan Rentang Gerak: 
Rentang gerak sendi siku pasif dan aktif 
 
Latihan Isometris: 
Fleksor/ekstensor pergelangan tangan  
Dilakukan 10-12 repetisi, 3set 
 
 
Tahan 10 detik, dilakukan 3 set 
Terapi manual: 
Pemijatan pada area otot yang kaku dan 
tegang 
Dilakukan oleh Fisioterapi selama 10-15 
menit 
Terapi modalitas: 
TENS (Transcutaneous Electrical Nerve 
Stimulation)  
 
Penggunaan Ultrasound 
 
Dilakukan selama 15 menit 
 
Dilakukan selama 10 menit 
Terapi tambahan jika pasien datang 
dalam keadaan bengkak: 
 
Terapi Es, kompres  
 
 
 
Dilakukan selama 15 menit 
 
Diagnosis 
BACK PAIN 
Program Terapi & Latihan 
Waktu Pengerjaan (menit) 
Latihan Isometris: 
Abdominal Isometrik 
 
Latihan Peregangan: 
Knee to Chest (single & double), Pelvic 
Twist, Hamstring Bridge, Cat & Camel, 
Cobra & Childpose 
Tahan selama 10 detik, Dilakukan sebanyak 
3 set 
 
 
Tahan selama 15 detik, dilakukan sebanyak 
3 set 
 

CONFIDENTIAL 
 
PROTOCOL: CT_CTPPXM001_PRT_V003/IX/2025 
 
Page 51 of 51 
 
                      
                         
Terapi manual: 
Pemijatan pada area otot yang kaku dan 
tegang 
Dilakukan oleh Fisioterapi selama 10-15 
menit 
Terapi modalitas: 
TENS (Transcutaneous Electrical Nerve 
Stimulation)  
 
Penggunaan Ultrasound 
 
Dilakukan selama 15 menit 
 
Dilakukan selama 10 menit