Study to evaluate the bioequivalence of Diclofenac diethylamine gel, 1.16% in subjects with Osteoarthritis Degenerative joint disease of the knee.
Scientific Title of Study
A Randomized, Double-Blind, Multicenter, Three-Arm, Placebo-Controlled, Parallel-Design,
Bioequivalence Study with Clinical Endpoints comparing Diclofenac Diethylamine Gel 1.16% of
Encube Ethicals Private Limited, India with Voltaren Schmerzgel 11.6 mg/g (Diclofenac
Diethylamine Gel 1.16%) of GlaxoSmithKline GmbH & Co. KG, 80258, Munich, Germany in
Patients with Osteoarthritis (OA) of the Knee.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
ENC-002-DIC-OST, Version 1.0, Date: 28 August 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Jayashri Krishnan
Designation
Vice President
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
JSS Medical Research Asia Pacific Private Limited, No. A-39, 5th Cross Street, Hindu Colony, Nanganallur Chennai, Tamil Nadu India, 600061
Chennai TAMIL NADU 121003 India
Phone
09771407484
Fax
Email
jayashri.krishnan@jssresearch.com
Details of Contact Person Scientific Query
Name
Dr Sathish Kumar P
Designation
Medical Monitor
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
JSS Medical Research Asia Pacific Private Limited
No. A-39, 5th Cross Street, Hindu Colony, Nanganallur Chennai, Tamil Nadu India, 600061
Chennai TAMIL NADU 600061 India
Phone
7358005866
Fax
Email
sathish.p@jssresearch.com
Details of Contact Person Public Query
Name
Dr Neeraj Prasad
Designation
Deputy Director- Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
JSS Medical Research Asia Pacific Private Limited
302, 3rd Floor, C5, Fenkin9 Nr, Satkar Grande Hotel,
Wagle Estate Road, Near Automatic, Thane West, Thane
Mumbai, Maharashtra 400080, India
Thane MAHARASHTRA 400080 India
Phone
9930740633
Fax
Email
neeraj.prasad@jssresearch.com
Source of Monetary or Material Support
Encube Ethical Private Limited, India
Primary Sponsor
Name
Encube Ethical Private Limited, India
Address
Encube Ethical Private Limited, India,
Unit No. 24, Steelmade Industrial Estate,
Marol Village, Andheri (E),
Mumbai – 400 059 Maharashtra, India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
JSS Medical Research Asia Pacific Private Limited
Tower 2, 1st Floor, South Wing, L&T Business Park,
Plot no 12/4, Sector 27 D,
Delhi Mathura Road, Near Sarai Khawaja Metro Station,
Faridabad -121003, Haryana, India
All India Institute of Medical Studies
Room No 219, 2nd Floor, Department No 216, Plot No 2, Sector -20 Mihan, Sumthana, Nagpur- 441108, Maharashtra, India Nagpur MAHARASHTRA
9422904819
samirdwidmuthe@aiimsnagpur.edu.in
Dr Sharad Purohit
Asian Superspeciality Hospital Pvt. Ltd
Clinical Research Department, 6th Floor, Room no. 605, Asian Superspeciality Hospital Pvt. Ltd.
Kshitij Aria, Opp. Golden Triangle, Sardar Patel Stadium
Road, Navarangpura, Ahmedabad – 380014, Gujarat, India Ahmadabad GUJARAT
09879007908
dr_sharadpurohit@hotmail.com
Dr Amit Kale
D.Y. Patil Medical College Hospital and Research Centre, Pune
Room No. 10, High-tech building 1st floor, Dept. of Orthopedic, Dr. D.Y. Patil Medical College Hospital and Research Centre Pimpri, Pune-411018 Pune MAHARASHTRA
9423585027
dramitkale@rediffmail.com
Dr K Sanjeev Kumar
Govt. Medical College and Govt. General Hospital
Department of Orthopaedics, OPD No: 03, Ground floor, Government Medical College & Government General Hospital, Srikakulam -532001, A.P. India Srikakulam ANDHRA PRADESH
7702288992
drsanjeevkumarkare@yahoo.com
Dr Dhondiram Kshirsagar
Imperial Multi Specialty Hospital
Department of Orthopedic, Ground Floor, OPD No.1, Imperial Multi Specialty Hospital, Gate No. 1193, Pingale Parle, Nr. Radha Swami Ashram, Chikhali, Pune-411062, Maharashtra, India. Pune MAHARASHTRA
9850330336
dr.kshirsagard@gmail.com
Dr Alok Kumar Kalyani
Institutional Ethics Committee Maharaja Agrasen Hospital, New Delhi
Department of Rheumatology, Ground Floor, Room. No.5, Maharaja Agrasen Hospital, New Delhi West Punjabi Bagh New, Delhi-110026 New Delhi DELHI
01140777777
alokkalyani@gmail.com
Dr Rakesh Verma
Jawahar Lal Nehru Medical College
Research Department, 1st floor, Room No. 1, JLN Medical College, Kala Bagh, Ajmer-305001, Rajasthan, India Ajmer RAJASTHAN
9460195960
rakeshverma.jln@outlook.com
Dr P Ashok Kumar
King George Hospital
Superintendent, Prof. of Orthopaedics, Department of Orthopaedics, OPD No: 10, Ground floor, King George Hospital, Visakhapatnam -530002, A.P, India Visakhapatnam ANDHRA PRADESH
9849123602
amcorthopaedics@hotmail.com
Dr Sameer Haveri
KLES Dr. Prabhakar Kore Hospital & Medical Research Centre
Department of Orthopedic, Ground Floor, OPD No. 4, KLES Dr. Prabhakar Kore Hospital & Medical Research
Centre Nehru Nagar, Belagavi – 590010, Karnataka, India. Belgaum KARNATAKA
09844433082
drsameerhaveri@gmail.com
Dr Hrishikesh Padmakar Patkar
Lifepoint Multispecialty Hospital
Clinical Research Department, 3rd Floor, Room No. 1, Lifepoint Multispecialty Hospital,
145 1, Mumbai-Bangalore Highway, Near Hotel Sayaji,
Wakad, Pune 411057, Maharashtra, India.
Pune MAHARASHTRA
Malabar Medical College Hospital and Research Center
OP room no 17-1st floor, Department of Orthopaedics, Malabar Medical College Hospital and Research, Centre, P.O. Modakkallur, Atholi, Kozhikode-673323, Kerala, India
Kozhikode KERALA
8891000510
drravindranmk@gmail.com
Dr Mohan MR
Nano Hospital
Department of Orthopedic, Ground Floor, Room No. 1, Nano Hospitals, #79, Sir M Visveswaraya Road, Near Arekere Sai Baba Temple, Off
Bannerghatta Road, Bengaluru 560076.
Bangalore KARNATAKA
9686823666
Mohan_ortho@yahoo.com
Dr Shushil Mankar
NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital and Research Institute
Department of Orthopedic, 1st Floor, Room No.2, NKP Salve Institute of Medical Sciences and Lata
Mangeshkar Hospital and Research Institute Digdoh Hills, Hingna Road, Nagpur,
Maharashtra- 440019
Nagpur MAHARASHTRA
9422108284
drshmankar@gmail.com
Dr Anand Mondal
NRS Medical College & Hospital
OPD Building, Ground Floor Room No.13 NRS Medical College & Hospital 138 A.J.C. Bose Road, Kolkata - 700014 West Bengal India Kolkata WEST BENGAL
9434342451
dranandarortho@yahoo.in
Dr Pratik Vinchhi
Parth Hospital
Department of Orthopedic, 4th Floor, Room No 407 E405 Parth Hospital, Galaxy Arcade, Near Galaxy Cinema, Naroda, Ahmedabad, Gujrat 382330 Ahmadabad GUJARAT
Sancheti Institute for Orthopedics & Rehabilitation
Chairman office, 4th Floor, Room No.116, Sancheti Institute for Orthopedics & Rehabilitation Shivajinagar, Pune, Maharashtra- 411005, India Pune MAHARASHTRA
8888553333
parag@sanchetihospital.org
Dr Parag Sancheti
Sancheti Institute for Orthopedics & Rehabilitation
Chairman office, 4th Floor, Room No.116, Sancheti Institute for Orthopedics & Rehabilitation Shivajinagar, Pune, Maharashtra- 411005, India Pune MAHARASHTRA
CR Project Room, administrative block, 2nd Floor, Department of Orthopedic, Visakha Institute of Medical Sciences, Hanumauthwaka, Vishakapatnam-530040, Andhra Pradesh, India
Visakhapatnam ANDHRA PRADESH
Ethics Committee, Dr. D.Y. Patil Vidyapeeth Pimpri, Sant Tukaram Nagar Pune, Maharashtra- 411018, India
Approved
Ethics Committee, N.R.S. Medical College, NRS Medical College 138, A.J.C Bose Road Kolkata, Kolkata West Bengal – 700014, India.
Approved
IEC, NKP Salve Institute of Medical Sciences, and Lata Mangeshkar, DigdohHills, Hingna Road, Nagpur, Maharashtra- 440019, India
Approved
Imperial Ethics Committee Imperial Multispecialty Hospital, GAT No. 1193, Pingale Pride, Haveli, Pune Pimpri, Chinchwad, Maharashtra GAT No. 1193, Pingale Pride, Haveli, Pune Pimpri, Chinchwad, Maharashtra -411062 India
Approved
Institutional Ethics Committee for Clinical Trial, All India Institute of Medical Studies, Plot No 2, Sector -20 Mihan, Sumthana, Nagpur- 441108, Maharashtra, India
Approved
Institutional Ethics Committee Government Medical College & Government General Hospital, Research Wing, 2nd Floor, Beside FM Ward, Srikakulam-532001, Andhra Pradesh, India
Approved
Institutional Ethics Committee, Jawahar Lal Nehru Medical College, Kala Bagh, Ajmer, Rajasthan – 305001, India
Approved
Institutional Ethics Committee, King George Hospital, Visakhapatnam- 530002, Andhra Pradesh, India
Approved
Institutional Ethics Committee, KLE University KLE University KLE Dr.PK Hospital and MRC Nehru Nagar Belagavi Belagavi Belagavi
Approved
Institutional Ethics Committee, Maharaja Agrasen Superspeciality Hospital, Sector 7, Central Spine, Vidyadhar Nagar, Jaipur, Rajasthan - 302039, India.
Approved
Institutional Ethics Committee, Sancheti Institute for Orthopaedics and Rehabilitation, 16, Shivajinagar, Pune, Maharashtra- 411005, India
Approved
Institutional Ethics Committee, Visakha Institute of Medical Sciences, Hanumanthwaka, Chinnagadhili, Visakhapatnam-530040, Andhra Pradesh, India
Approved
Institutional Human Ethics Committee Malabar Medical College Hospital and Research Centre, Modakkallur Atholi, Kozhikode- 673323, Kerala, India
Sri Durgamba Independent Ethics Committee, 5th cross 5th stage Kamakya layout Banashankari same as address line 1 Bangalore, Bengaluru (Bangalore) Rural Karnataka – 560085, India
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: M179||Osteoarthritis of knee, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Diclofenac Diethylamine Gel 1.16%
The interventional product will be assigned to Each subject and will be instructed to
apply approximately 4 g to the target knee, four times a day for 4 weeks.
Comparator Agent
Voltaren Schmerzgel 11.6 mg/g (Diclofenac Diethylamine Gel 1.16%)
The Comparator agent will be assigned to Each subject and will be instructed to
apply approximately 4 g to the target knee, four times a day for 4 weeks.
1.Males or non-pregnant, non-lactating females aged ≥ 35 years with a clinical diagnosis of
osteoarthritis of the knee according to the American College of Rheumatology criteria, i.e.
Knee pain along with at least 3 of the following 6 criteria (Appendix I)
Age > 50 years
Stiffness < 30 minutes
Presence of crepitus
Bony tenderness
Bony enlargement
No palpable warmth
2. Symptoms in the target knee for at least 6 months prior to screening
3. Knee pain for 15 days of the preceding month (periarticular knee pain due to osteoarthritis and
not due to other conditions such as bursitis, tendonitis, etc.)
4. The pain in the target knee required the use of nonsteroidal anti-inflammatory drugs (NSAID)
5.Patients having an X-ray of the target knee, taken no more than 1 year before baseline, showing
evidence of OA with Kellgren-Lawrence grade 1-3 disease (Appendix no. II)
Note: If a digital x-ray (both anterior-posterior and lateral view) of the target knee taken no
more than 1 year before baseline is available then the findings of the available x-ray will be considered for evaluation and no repeat x-ray will be performed.
6. After discontinuation of all pain medications for at least 7 days (Placebo run-in period), have
found at least moderate pain on movement (POM) for the target knee, defined as a baseline.
score of ≥ 50 mm on a 0-100 mm Visual Analog Scale (VAS) immediately prior to
randomization (Appendix III)
7. After discontinuation of all pain medications for at least 7 days (Placebo run-in period), a
baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Likert,
Version 3.1) pain subscale of ≥ 9 immediately prior to randomization (Appendix IV)
8. Able to replace all current pain medications with acetaminophen for use as needed during the
duration of the study [subject should be able to withhold all rescue medication (e.g.,
acetaminophen) use for at least 48 hours prior to all WOMAC pain score assessments at study.
visits
9. Change in the total WOMAC pain subscale score for the target knee ≤ 2 from Visit 2 (Start of
Placebo Run-in period) to Visit 3 (Baseline/Randomization).
10. Subjects who can read and understand the WOMAC pain sub-scale.
11. Patients who are able to understand the investigational nature of this study and able to provide
a written informed consent form
12. Patients who are willing and able to comply with all the study assessments and adhere to the
protocol schedule
13. If female, the patient must be either postmenopausal for at least one year prior to randomization,
surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or
practicing the following methods of birth control:
o Oral Contraceptives or Intrauterine Devices in place for at least 3 months prior to the
start of the study and remaining in place during the study period, or
o Double Barrier methods containing or used in conjunction with a spermicidal agent, or
o Contraceptive Patches/ Implants, or
o Abstinence: Subjects who will be practicing abstinence will agree to have a documented
second acceptable method of birth control if the subject becomes sexually active during
the course of her study participation.
ExclusionCriteria
Details
1. Known history or presence of hypersensitivity or allergic reaction to Diclofenac, aspirin,
acetaminophen, or other NSAIDs, or any other inactive ingredients used in the study product
2. Females who are pregnant or lactating or planning to become pregnant during the study period
3. The X-ray confirmed Kellgren-Lawrence Grade 4 disease of Osteoarthritis
4. History of OA pain in the contralateral knee requiring medication (OTC or prescription) within
1 year prior to screening
5. After discontinuation of all pain medications for at least 7 days (Placebo run-in period), had a
baseline score of ≥ 20 mm on a 0-100 mm VAS for the contralateral knee immediately prior to
randomization
6. History of OA of either Hip or Hands.
7. History or presence of secondary OA (e.g. Congenital, traumatic, gouty arthritis), rheumatoid
arthritis
8. History or presence of chronic inflammatory disease (e.g. colitis) or fibromyalgia
9. Symptomatic peripheral vascular disease of the study leg (prior or current).
10. Any musculoskeletal condition that would impede measurement of efficacy at the target knee
11. History of regular headaches or backache or condition that warrants frequent use of
acetaminophen (paracetamol) or NSAIDs within the previous year.
12. Concomitant skin disease at the application site may affect study drug application or tolerability
evaluation.
13. History of active asthma within the previous year that may require periodic treatment with
systemic steroids during the study period (note: inhaled steroids for this condition are allowed).
14. History of uncontrolled hypertension (blood pressure more than 150/100 mm of Hg) in spite of
treatment within the previous year and/or any other clinically significant vital sign abnormality.
15. History of aspirin-sensitive asthma
16. History of myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired
renal function (Serum creatinine > 1.5 x ULN), or liver disease within 1 year of randomization
17. History of gastrointestinal bleeding or peptic ulcer disease in the last year
18. Use of anticoagulants, ACE-inhibitors, cyclosporine, diuretics, lithium, or methotrexate within
the past month prior to entry into the study
19. Elevated transaminases (≥ 3 times ULN) and hemoglobin < 9.0 g/dL at screening
20. Concomitant use of intra-articular corticosteroids, systemic corticosteroids, topical
corticosteroids, or immunosuppressive drugs or their use prior to 30 days of screening
21. Concomitant acetylsalicylic acid therapy other than a stable low dose used for cardiac
prophylaxis (maximum 162 mg daily) was taken for at least 3 months prior to enrolment and
maintained throughout the duration of the study.
22. History of major surgery or previous damage to the study knee at any time, or minor knee
surgery (e.g. any surgery other than major surgery including, but not limited to, cartilage repair,
collateral ligament repair, or arthroscopic debridement) to the study knee within 1 year prior to
screening
23. Visco-supplementation in any joint including the target knee within 6 months prior to
screening.
24. Tense effusion requiring aspiration.
25. Known history of positive serology test i.e., HIV, HCV, or HBsAg
26. Involved in clinical trials and taken investigational drugs within 30 days of enrolment
27. Subjects with HbA1c ≥ 8 %
28. Subjects with BMI more than 40 kg/m2.
29. Subjects of any other severe acute or chronic medical conditions or abnormal laboratory
findings, that may increase the risk in the participation of the study or could compromise the
integrity of study data based on the judgment of the study Investigator.
30. History of alcohol or other substance abuse within the last year
31. Inability to understand the requirements of the study and the relative information or are unable
or unwilling to comply with the study protocol.
32. Lives in the same household as currently enrolled subjects.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
Mean Change in the total WOMAC pain subscale score for the target knee.
Total Sample Size="942" Sample Size from India="942" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The study is a Randomized, Double-Blind, Multicenter, Three-Arm,
Placebo-Controlled, Parallel-Design, Bioequivalence Study with Clinical
Endpoints comparing Diclofenac Diethylamine Gel 1.16% of Encube Ethicals
Private Limited, India with Voltaren Schmerzgel 11.6 mg/g (Diclofenac
Diethylamine Gel 1.16%) of GlaxoSmithKline GmbH & Co. KG, 80258, Munich,
Germany in Patients with Osteoarthritis (OA) of the Knee.
The following are the main objectives of this clinical end-point
bioequivalence study.
To evaluate bioequivalence (with clinical endpoints) of Diclofenac
Diethylamine Gel 1.16% of
Encube Ethicals Private Limited, India with Voltaren Schmerzgel 11.6
mg/g (Diclofenac
Diethylamine Gel 1.16%) of GlaxoSmithKline GmbH & Co. KG, 80258,
Munich, Germany in
Patients with Osteoarthritis (OA) of the Knee
To evaluate the superiority of two active treatments (Test and
Reference) to the placebo in Patients with Osteoarthritis (OA) of the Knee
To assess the safety and tolerability of the study treatments