Bioequivalence study with clinical endpoint of generic diclofenac gel with
Voltaren® gel in patients with osteoarthritis of knee.
Scientific Title of Study
A Randomized, Double blind, Three-arm, Parallel, Placebo-controlled, Clinical
Study to Evaluate the Bioequivalence using Clinical Endpoint of Diclofenac
Sodium Gel, 1% (Mylan Inc.) versus Voltaren® Gel (Diclofenac Sodium Topical
Gel) 1% (Novartis Consumer Health, Inc.) in Patients with Osteoarthritis (OA) of
the Knee.
Ajanta Research Centre, Ajanta Hospital and IVF Centre, Department of Orthopaedics, 765, ABC Complex, Kanpur Road, Alambagh, Lucknow 226005, Uttar Pradesh Lucknow UTTAR PRADESH
9559782773
dr.rajeshkgmc@gmail.com
Dr Amit Patel
Anand Multispeciality Hospital
Department of Orthopaedics, Anand Multispeciality Hospital, B-Tower, Sundervan Complex, Near Gorwa ITI, Gorwa, Beside IOCL petrol pump, Vadodara-390016, Gujarat Vadodara GUJARAT
9824455237
amhbaroda@gmail.com
Dr Kaushal Anand
B.J Medical College & Civil Hospital
Orthopaedic Department, B.J Medical College & Civil Hospital, Asarva, Ahmedabad-380016, Gujarat Ahmadabad GUJARAT
9909013564
kaushal87anand@gmail.com
Dr Pramodini Vasant Shankaran
Bhaktivedanta Hospital and Medical Research
BhaktiVedanta Hospital and Research Institute, Srishti Complex, Bhaktivedanta Swami Marg, Mira Road East, Thane, Maharashtra-401107 Thane MAHARASHTRA
9820317030
shankarankrishnan@yahoo.com
Dr Amit Kale
BJ medical college & Sassoon General HospitalÂ
BJ Medical College Sassoon General Hospital, Dept of Orthopedics,Orthopedic Building, 2nd Floor, HOD Room, Sassoon Road, Near Railway Station, Pune - 411001 Pune MAHARASHTRA
9423585027
dramitkale@rediffmail.com
Dr Somesh Prakashbhai Singh
GMERS Medical College & Civil Hospital
Dept. of Orthopaedics, GMERS Medical College & Civil Hospital , Near Gujarat High Court, S. G. Highway, Ahmedabad 380061, Gujarat Ahmadabad GUJARAT
9825370446
drsomeshsingh@yahoo.com
Dr M K Ravindran
Government Medical College
Government Medical College, Department of Orthopaedics, Ward No. 24, Kozhikode, Kerala-673008 Kozhikode KERALA
9447023525
raveendranmk@gmail.com
Dr Sajal R Mitra
Government Medical College and Hospital
Government Medical College and Hospital , Dept of Orthopedics, OT-E, Opp. Ward No. 26, 1st Floor Nagpur-440003, Maharashtra Nagpur MAHARASHTRA
9373114929
sajalmitra2007@yahoo.co.in
Dr Mohammed Asharaf Mammatharayan Illah
Governmentt T.D Medical College
Department of Orthopaedics, Governmentt T.D Medical College, Vandanam, Alappuzha, Kerala 688005 Alappuzha KERALA
04772251611
drashraf369@yahoo.com
Dr Tholgapiyan T
Govt Stanley Medical College & Hospital
Dept. of Orthopaedic Surgery, Govt Stanley Medical College & Hospital, Old Jail Road, Royapuram, Chennai - 600001, Tamil Nadu Chennai TAMIL NADU
9048104673
stanelyresearch16@gmail.com
Dr Eknath Pawar
Grant Government Medical College & Sir J J Group of hospital
Department of Orthopaedics, Grant Government Medical College & Sir J J Group of hospital, Byculla, Mumbai 400008, Maharashtra Mumbai MAHARASHTRA
8551996777
drpawared2003@yahoo.co.in
Dr Jagannath Sahoo
IMS and SUM Hospital
IMS and SUM Hospital
Department of Orthopaedics
K-8, Kalinga Nagar,
Bhubaneswar - 751003, Odisha Cuttack ORISSA
9439523875
drjsahoo@gmail.com
Dr Ananda Kisor Pal
Institute of Post Graduate Medical Education and Research (IPGMER)
Department of Orthopaedics, # 244, Institute of Post Graduate Medical Education and Research (IPGMER), AJC Bose Road, Kolkata 700020, West Bengal Kolkata WEST BENGAL
9831093244
orthoakpal@yahoo.com
Dr Smruti Ramteke
Jasleen Hospital
Department of Orthopaedics, Jasleen Hospital, Opp. Big Bazar, Panchsheel Square, Dhantoli, Nagpur-440012, Maharashtra Nagpur MAHARASHTRA
9823514680
sramteke@rediffmail.com
Dr A Ramakrishnam Naidu
King George Hospital
Department of Orthopedics, Unit - II, OP No. 10, King George Hospital, Andhra Medical College, Visakapatnam-530002, Andhrapradesh. Visakhapatnam ANDHRA PRADESH
9885093386
ramky@yahoo.com
Dr Ashish Kumar
King George Medical University
Department of Orthopaedic Surgery, King George Medical University, Lal Bahadur Shastri Bhawan, Nabiullah Road, RALC campus, Lucknow 226018, Uttarpradesh Lucknow UTTAR PRADESH
9415020202
drashish_kumar20202@yahoo.com
Dr Arvind Goregaonkar
Lokmanya Tilak Municipal Medical College & General Hospital
Lokmanya Tilak Municipal Medical College & General Hospital, Department of Orthopaedics, College Building, Second Floor, Room No. 2, Dr. B. R. Ambedkar Road, Sion, Mumbai - 400022 Mumbai MAHARASHTRA
9821351787
abgortho@hotmail.com
DrKunal Bhalla
M.V. Hospital & Research Centre
M.V. Hospital & Research Centre, 314/30, Mirza Mandi, Chowk, Lucknow-226003, UP Lucknow UTTAR PRADESH
8744009726
kunalicious_kunal@yahoo.com
Dr Sudipto Das
Medica Super Speciality Hospital
127, Orthopaedic Department, Medica Super Speciality Hospital, E. M. Bypass, Mukundapur, Kolkata 700099, West Bengal Kolkata WEST BENGAL
7044076893
sudipto.das@medicasynergie.in
Dr Jaykrushna Soni
Medistar Multispeciality Hospital
Department of Orthopaedics, Medistar Multispeciality Hospital, Trimurti Avenue, Medistar cross road, NH8, Industrial Area, Himmatnagar-383001, Sabarkantha, Gujarat. Sabar Kantha GUJARAT
9879291135
drjaykrishnasoni@yahoo.co.in
Dr Paramesh K C
Mysore Medical College and Research Institute
K. R. Hospital, Department of Orthopaedics, Mysore Medical College and Research Institute, Mysore, Karnataka-570001 Mysore KARNATAKA
9343055819
parameshkennal@gmail.com
Dr Sushil Mankar
NKP Salve, Institute of Medical sciences and Lata Mangeshkar
NKP Salve,
Institute of Medical sciences and Lata Mangeshkar,
Digdoh Hills,
Hingna Road,
Nagpur - 440019, India Nagpur MAHARASHTRA
9422108284 07104-232905 drshmankar@gmail.com
Dr Awdhesh Kumar Yadav
OM Research Center, OM Surgical Center & Maternity Home
SA-17/3, P-4, Sri Krishna Nagar,
Paharia, Ghazipur Road,
Varanasi-- 221007,
Uttar Pradesh, India Varanasi UTTAR PRADESH
Post Graduate Institute of Medical Education & Research (PGIMER)
Post Graduate Institute of Medical Education & Research (PGIMER), Dept. of Orthopaedics, sector 12, Chandigarh-160012 Chandigarh CHANDIGARH
9815712727
vijaygoni@gmail.com
Dr Gaurav Jugalkishore Rathi
Rathi Hospital
Rathi Hospital, Department of Orthopaedics, Clinical Reasearch Division, Basement Clinical Research Area, Nr Anupam Shopping Centre, Opp Mahabaleshwar Soc, Nr Jodhpur Cross roads, Satellite, Ahmedabad 380 015, Gujarat, India Ahmadabad GUJARAT
9824015618
drgjrathi@yahoo.co.in
Dr Jinesh Shah
Riddhi Medical Nursing Home
Orthopaedic Department, Riddhi Medical Nursing Home, A-101, Jalaram plaza, Near Jawahar chowk cross road, Maninagar, Ahmedabad 380008 Ahmadabad GUJARAT
9879531832
drjinesh123@gmail.com
Dr Parag Sancheti
Sancheti Institute for Orthopedics & Rehabilitation
Department of Orthopedics, Sancheti Institute for Orthopaedic & Rehabilitation, 1st floor, 16 Shivaji nagar Pune-411005, Maharashtra Pune MAHARASHTRA
9823553333
parag@sanchetihospital.org
Dr Sharad Purohit
Sanjivani Superspeciality Hospital Pvt. Ltd
Sanjivani Superspeciality Hospital Pvt. Ltd,OPD room Dept of orthopaedics 1, Uday Park Society, Nr. Sunrise Park, Vastrapur, Ahmedabad-380015, Gujarat Ahmadabad GUJARAT
9879007908
dr_sharadpurohit@hotmail.com
Dr Mohan Desai
Seth G.S Medical College and KEM Hospital
Orthopaedic Department, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai- 400012, Maharashtra Mumbai MAHARASHTRA
9892275697
drmohandesai@hotmail.com
Dr Harshal Kalariya
Shree Giriraj Multispeciality Hospital
Shree Giriraj Multispeciality Hospital, 150 Feet Ring Road, 27-Navjyot Park Main Road, Amin Marg Cross Road, Rajkot, Gujarat 360005 Rajkot GUJARAT
9879883331
harshalkalaria@gmail.com
Dr Rajiv Daveshwar
Sir Sayajirao General Hospital and Medical College
Dept. of orthopedics, Sir Sayajirao General Hospital and Medical College, Anandpura, Vadodara-390001, Gujarat Vadodara GUJARAT
9427322493
dr_rndaveshwar@yahoo.com
Dr Jiss Joseph Panakkal
Sree Narayana Institute of Medical Science
Sree Narayana Institute of Medical Science, Dept of Orthopedics, Chalakka, N.Kuthiyathodu, P.O. Eranakulam-683594, Kerala Ernakulam KERALA
04844020255
snims.research@gmail.com
Dr Rupraj Pawar
Supe Heart and Diabetes Hospital & Research Centre
Orthopaedic Department, Supe Heart and Diabetes Hospital & Research Centre, Opp Adharashram, Gharpure Ghat, Near Rungta High School, Ashok Stambh, Nashik 422002, Maharashtra Nashik MAHARASHTRA
9822060547
ruprajpawar@rediffmail.com
Dr Krishna Subrahmanya Kumar Pannala
Yashoda Hospital
Department of orthopaedics, Yashoda Hospital, Malakpet, Hyderabad 500 036, Andhrapradesh Hyderabad ANDHRA PRADESH
9246277646
subri_pannala@yahoo.co.in
Dr Sanjib Kumar Behera
Yashoda Hospital
Orthopaedic Department, Yashoda Hospital, Behind Hari Hara Kala Bhawan, Secunderabad 500003, Andhrapradesh Hyderabad ANDHRA PRADESH
BhaktiVedanta Hospital Ethics Committee, Bhaktivedanta HEC office, 6th floor, BhaktiVedanta Hospital and Research Institute, Srishti Complex, Bhaktivedanta Swami Marg, Mira Road(E), Thane, Maharashtra-401107, India.
Approved
Clinical Research Ethics Committee, Medica superspecialty Hospital, Kolkata, WB, India
Approved
Department of Orthopaedics, Jasleen Hospital, Opp. Big Bazar, Panchsheel Square, Dhantoli, Nagpur-440012, Maharashtra Nagpur MAHARASHTRA
Approved
Ethics Committee, Ajanta Hospital and IVF Centre, 765, ABC Complex, Kanpur Road, Alambagh, Lucknow-226005, Uttarpradesh, India.
Approved
GMERS Medical College & Civil Hospital, Dept. of Orthopedics, Ground floor, Room No. 5, Sola, Near Gujarat High Court, S. G. Highway, Ahmedabad 380061, Gujarat.
Approved
IEC-YAMER, BH harihara kala bhavan, Secundarabad, Andhra Pradesh
Approved
IEC-YAMER, BH harihara kala bhavan, Secundarabad, Andhra Pradesh
Approved
IEC-YAMER, BH harihara kala bhavan, Secundarabad, Andhra Pradesh
Approved
Institutional Ethics Committee for Human Research (IECHR), Dept. of Pharmacology, Medical College & SSG Hospital, Baroda-390001, Gujarat, India.
Approved
Institutional Ethics Committee for M.V. Hospital & Research Centre, 1st Floor, 314/30, Mirza Mandi, Chowk, Lucknow-226003, Uttar Pradesh, India.
Approved
Institutional Ethics Committee Grant Government Medical College & Sir J. J. Group of Hospitals, Byculla, Mumbai-400008, Maharashtra, India.
Approved
Institutional Ethics Committee of B.J. Government Medical College & Sassoon General Hospitals, Dept. of Pharmacology, B J Medical College, Sassoon Road, Near Railway Station, Pune-411001, Maharashtra, India.
Approved
Institutional Ethics Committee Sree Narayana Institute of Medical Science, ernakulam, Kerala
Approved
Institutional Ethics Committee, B.J Medical college & civil Hospital, Office of the Medical Superintendent, Civil Hospital, Ahmedabad-380 016, Gujarat, India
Approved
Institutional Ethics Committee, Dept. of Pharmacology, Govt. Medical College, Nagpur 440003, India.
Approved
Institutional Ethics Committee, Govt Stanley Medical College & Hospital, Old Jail Road, Royapuram, Chennai - 600001, Tamil Nadu
Approved
Institutional Ethics Committee, IMS and SUM Hospital, Bhubaneswar - 751003, Odisha, India
Institutional Ethics Committee, King George Hospital, Maharanipeta, Visakhapatnam-530002, Andhrapradesh, India.
Approved
Institutional Ethics Committee, King george university, Lucknow, Uttar pradesh
Approved
Institutional Ethics Committee, Mysore Medical College and Research Institute, Mysore, Karnataka-570001
Approved
Institutional Ethics Committee, NKPSIMS and Lata Mangeshkar
Approved
Institutional Ethics Committee, Om Surgical Center & Maternity
Approved
Institutional Ethics Committee, Rathi Hospital, Nr. Anupam Shopping Centre, Opp. Mahabaleshwar Soc, Nr. Jodhpur Cross Roads, Satellite, Ahmedabad-380015, Gujarat.
Approved
Institutional Ethics Committee- Human Research, Lokmanya Tilak Municipal Medical College Building, staff and research Society, Room No 17, 2nd Floor , Sion Mumbai- 400022
Parul University Institutional Ethics committee human Research, Waghodia, Vadodara
Approved
Riddhi Medical Nursing Home Institutional Ethics Committee,  A-101, Jalaram plaza, Near Jawahar chowk , Maninagar, Ahmedabad 380008, Gujarat, India.
Approved
Sancheti Institutional Review Board, Sancheti Institute for Orthopedics & Rehabilitation, 16, Shivaji nagar, Pune, 411005, Maharashtra, India
Approved
Sanjivani Hospital Ethics Committe, 1, Uday Park Society, Nr. Sunrise Park, Vastrapur, Ahmedabad-380015, Gujarat.
Approved
Shree Giriraj Hospital Research Ethics Committee, Ground Floor, 150 Feet Ring Road, 27-Navjyot Park Main Road, Rajkot-36005, Gujarat, India.
Approved
Supe Hospital Ethics Committee (SHEC), Supe Heart and Diabetes Hospital & Research Centre, Opp Adharashram, Gharpure Ghat, Near Rungta High School, Ashok Stambh, Nashik 422002, Maharashtra.
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Osteoarthritis (OA) of the Knee,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Diclofenac Sodium Gel, 1%
Mylan Inc.
Dose: 4 gm
Frequency: Four times a day
Route of Administration: Topical
Total Duration of Therapy: 4 weeks
Comparator Agent
Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%
Novartis Pharma Produktions GmbH.
Dose: 4 gm
Frequency: Four times a day
Route of Administration: Topical
Total Duration of Therapy: 4 weeks
Inclusion Criteria
Age From
35.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Healthy male or non-pregnant female aged ≥ 35 years with a clinical diagnosis of OA of the knee according to the American College of Rheumatology (ACR) criteria i.e. Knee pain along with at least 3 of the following 6 criteria
a. Age > 50 years
b. Stiffness < 30 minutes
c. Presence of crepitus
d. Bony tenderness
e. Bony enlargement
f. No palpable warmth
2. Symptoms in target knee for at least 6 months prior to screening
3. Knee (not referred) pain in target knee for 15 days of the preceding month (periarticular knee pain due to OA and not due to other conditions such as bursitis, tendonitis, etc.)
4. Pain in the target knee requiring the use of NSAIDs or acetaminophen/paracetamol (topical or oral treatments).
5. Subject 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.
6. After discontinuing all pain medications (placebo run – in period) for at least 7 days, had at least moderate pain on movement (POM) for target knee, defined as a baseline score of ≥ 50 mm on a 0-100 mm Visual Analog Scale (VAS) immediately prior to randomization
7. After discontinuing all pain medications (placebo run – in period) for at least 7 days has a baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Likert (version 3.1)) pain subscale of ≥9 immediately prior to randomization.
8. Able to tolerate rescue medication with acetaminophen (paracetamol) taken as l-2 tablets up to a maximum 2 gm per day for the duration of the study.
9. Subjects who can read and understand WOMAC pain sub scale.
10. If female, 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:
a) Oral Contraceptives or Intrauterine Device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or
b) Double Barrier methods containing or used in conjunction with a spermicidal agent, or
c) Contraceptive Patches/ Implants, or
d) Abstinence: Subjects who will be practicing abstinence will agree to have a documented second acceptable method of birth control if the subject become sexually active during the course of her study participation.
ExclusionCriteria
Details
1. Pregnant or lactating or planning to become pregnant during the study period.
2. X-ray showing evidence of OA with Kellgren-Lawrence grade 4 disease.
3. History of OA pain in the contralateral knee requiring medication (OTC or prescription) within 1 year prior to screening.
4. After discontinuing all pain medications (placebo run-in period) for at least 7 days, had a baseline score of ≥ 20 mm on a 0-100 mm Visual Analog Scale (VAS) for the contralateral knee immediately prior to randomization.
5. History of OA of either Hip or Hands
6. History of secondary OA (e.g. congenital, traumatic, gouty arthritis), rheumatoid arthritis.
7. History of chronic inflammatory disease (e.g., colitis) or fibromyalgia.
8. History of Drugs or Alcohol abuse within the previous year.
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 which warrants often use of acetaminophen (paracetamol) within the previous year.
12. Concomitant skin disease at the application site which 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 aspirin sensitive asthma.
15. History of uncontrolled hypertension (blood pressure more than 150/100 mm of Hg) in spite of treatment within the previous year.
16. History of myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function (Serum creatinine > 1.5 x ULN) or liver disease within the previous year.
17. History of coronary artery bypass graft within 6 months of screening.
18. History of gastrointestinal bleeding or peptic ulcer disease in last one year.
19. Known allergy to aspirin, nonsteroidal anti-inflammatory drugs (NSAID) or acetaminophen (paracetamol).
20. Elevated transaminases (≥ 3 times ULN) and Hemoglobin ˂ 9.0 g/dL at screening.
21. Viscosupplementation in any joint including the target knee within 6 months prior to screening
22. Receiving physical therapy (at an outpatient/clinic setting) for the lower extremities or having received physical therapy for the lower extremities within 1 month before screening.
23. Use of anticoagulants, ACE-inhibitors, cyclosporine, diuretics, lithium, or methotrexate prior to 30 days of screening.
24. Concomitant use of intra articular corticosteroids, systemic corticosteroids, topical corticosteroids, or immunosuppressive drugs or their use prior to 30 days of screening.
25. Concomitant acetylsalicylic acid therapy other than a stable low dose used for cardiac prophylaxis (maximum 162 mg daily) taken for at least 3 months prior to enrollment and maintained throughout the duration of the study.
26. 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.
27. Known history of positive HIV, HCV, or HBsAg.
28. Tense effusion requiring aspiration.
29. Subjects who have been treated with an investigational drug or investigational device within a period of 30 days prior to enrollment.
30. Any other acute or chronic illness that could compromise the integrity of study data or place the subject at risk by participating in the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Other
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
• Mean change in the total WOMAC pain subscale score for the target knee, from baseline to week 4
• Mean change in the total WOMAC pain subscale score for the target knee, from baseline to week 4
Secondary Outcome
Outcome
TimePoints
• Mean change in the total WOMAC pain subscale score for the target knee, from baseline to week 2.
• Mean change in the WOMAC pain subscale score at week 4 for subgroup subjects whose baseline WOMAC pain score less than or equal to 10.
2 and 4 week
Target Sample Size
Total Sample Size="1212" Sample Size from India="1212" Final Enrollment numbers achieved (Total)= "1220" Final Enrollment numbers achieved (India)="1220"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Patients with Osteoarthritis (OA) of the Knee
Primary Objective
1. To determine the clinical equivalence of Test Drug(Diclofenac sodium gel of 1% of Mylan Inc.) with the Reference Listed Drug (RLD)(Voltaren® Gel 1% of Novartis Consumer Health, Inc.) as measured by mean change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Likert (version 3.1) pain score.
2. To establish superiority of the Test Drug and Reference Listed Drug (RLD) over placebo in mean change from baseline in the WOMAC Likert (version 3.1) pain score.
Secondary Objectives
1. To assess the safety and tolerability of study treatments.
2. To determine the clinical equivalence of Test Drug (Diclofenac Sodium gel) with the Reference Listed Drug (RLD)(Voltaren® Gel) as measured by mean change from baseline in subjects whose baseline WOMAC Likert (version 3.1) pain scores are less than or equal to 10.