This is a clinical trial to compare clinical efficacy, safety and tolerability of generic Diclofenac Sodium Topical Gel 1%, with Voltaren® Gel (a Diclofenac Sodium Topical Gel 1%) and Vehicle of Diclofenac Sodium Topical Gel 1% in subjects with osteoarthritis(degenerative joint disease) of the knee
Scientific Title of Study
A Prospective, Multi-Center, Randomized, Double-Blind, Vehicle-Controlled, Parallel-Group Bioequivalence Study with Clinical Endpoints Comparing Generic Diclofenac Sodium Topical Gel 1% of Cipla Ltd., India to Voltaren® Gel (a Diclofenac Sodium Topical Gel 1%) of Endo Pharmaceuticals Inc., USA in Subjects with Osteoarthritis of the Knee.
Orthopedic Department,Asarwa,Ahmedabad-380016, Gujarat, India Ahmadabad GUJARAT
9879517351
drkaps@rediffmail.com
Dr Pramodini Shankaran
Bhakti Vedanta Hospital and Research Institute,
Bhakti Vedanta Hospital and Research Institute, Srishti Complex, Bhakti Vedanta Swami Marg, Mira Road East, Thane Maharashtra, India 401107 Thane MAHARASHTRA
9022145499
drparag@bhaktivedanthospital.com
Dr Patil Sanjay Ningangouda
Bharati Hospital and Research Center
Department of Orthopedics, Room No 14, Ground floor, Bharati Hospital and research center, Pune-Satara Road, Dhankawadi, PIN Code- 411043, India Pune MAHARASHTRA
91-20-40555555
drsanjaypatil10@gmail.com
Dr Sajal R Mitra
Govt. Medical College and Hospital
Department Of Orthopedics,
Govt. Medical College and Hospital, Nagpur-440003
Nagpur MAHARASHTRA
8446267317
sajalmitra2007@yahoo.co.in
Dr Smruti Sanjay Ramteke
Jasleen Hospital
Opp. Big Bazar, Panchsheel Square, Dhantoli, PIN Code-440012, India Nagpur MAHARASHTRA
91-712-2458303
sramteke@rediffmail.com
Dr Amit Sharma
Krishna Shalby Hospital
Krishna Shalby Hospital,
319, Green City, Ghuma, Via Bopal,
Ahmedabad, 380058, Gujarat India
Ahmadabad GUJARAT
(1) ICD-10 Condition: M17||Osteoarthritis of knee,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Generic Diclofenac Sodium Topical Gel 1%
Dosage form: Topical Gel,
Dose: 16 g a day,
Frequency of drug administration: 4g four times a day,
Duration of treatment: 4 weeks.
Comparator Agent
Vehicle of Diclofenac Sodium Topical Gel 1%
Dosage form: Topical Gel,
Dose: 16 g a day,
Frequency of drug administration: 4g four times a day,
Duration of treatment: 4 weeks.
Comparator Agent
Voltaren Gel 1%
Dosage form: Topical Gel,
Dose: 16 g a day,
Frequency of drug administration: 4g four times a day,
Duration of treatment: 4 weeks.
Inclusion Criteria
Age From
35.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
A subject will be eligible for inclusion in the study if he / she fulfils the following criteria:
1. 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:
a. Pain in the knee and presence of at least 3 of the following ACR criteria: age ≥ 50 years; stiffness lasting for < 30 min; bony tenderness; crepitus; bony enlargement; no palpable warmth, and including:
i. Symptoms for at least 6 months prior to screening, and
ii. Knee (not referred) pain for 15 days of the preceding month (periarticular knee pain due to OA and not due to other conditions such as bursitis, tendonitis, etc.), and
iii. The pain in the target knee required the use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen / paracetamol (topical or oral treatments)
2. Had 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
3. After discontinuing all pain medications for at least 7 days, had at least moderate POM for target knee, defined as a baseline score of ≥ 50 mm on a 0-100 mm VAS immediately prior to randomization, and a baseline WOMAC pain subscale of at least 9 immediately prior to randomization
4. Able to tolerate rescue medication (i.e., acetaminophen / paracetamol)
5. Subjects willing to refrain from using any other OA treatment during the 4-week treatment period, other than the study treatment, and rescue medication
6. Subjects willing to give written informed consent and provide audio-visual recording of the consent process
7. Willing and able to comply with the study requirements
8. Not pregnant / not planning to be pregnant / not a lactating female. Women of childbearing potential and male subjects were included in the study if they are willing to use an appropriate method of contraception
ExclusionCriteria
Details
A subject will not be eligible for inclusion in this study if he / she meets any of the following criteria:
1. X-ray showing evidence of OA with Kellgren-Lawrence grade 4 disease
2. History of OA pain in the contralateral knee requiring medication within 1 year prior to screening
3. After discontinuing all pain medications for at least 7 days, had a baseline score of ≥ 20 mm on a 0-100 mm VAS for the contralateral knee immediately prior to randomization
4. History of secondary OA, rheumatoid arthritis, chronic inflammatory disease (e.g., colitis) or fibromyalgia
5. History of asthma, hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function or liver disease
6. History of gastrointestinal (GI) bleeding or peptic ulcer disease
7. Known allergy to aspirin or NSAID
8. Elevated transaminases at screening (i.e., AST or ALT more than 2 times the upper limit of normal at screening visit)
9. Use of anticoagulants, ACE-inhibitors, cyclosporine, diuretics, lithium, or methotrexate within the past 30 days prior to entry into the study
10. Concomitant acetyl salicylic acid therapy other than a stable low dose used for cardiac prophylaxis (max 162 mg daily) taken for at least 3 months prior to enrolment and maintained throughout the duration of the study
11. Any other topical products applied to the target site
12. Use of systemic corticosteroid or immunosuppressive drugs
13. Use of pain medication other than acetaminophen / paracetamol
14. Any other acute or chronic illness that in the opinion of the investigator could compromise the integrity of the study data or place the subject at risk by participating in the study
15. Receipt of any drug as a part of a research within 30 days prior to screening
16. Previous participation in this study
17. Recent history of knee injury or surgery
18. Subjects who are alcohol or drug dependent i.e. substance of abuse
19. Subjects having clinically significant liver, kidney, or cardiac dysfunction
20. Subjects having history of hypersensitivity reactions to diclofenac sodium gel or any of its excipients
21. A positive serology test result for HIV antibody (I & II), HBsAg, and / or HCV antibodies
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
The primary efficacy endpoint of the study is:
Mean change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score in target knee from baseline to week 4.
4 weeks.
Secondary Outcome
Outcome
TimePoints
The secondary efficacy endpoints of the study are:
Mean change in pain on movement (POM) on a Visual Analog Scale (VAS) for target knee from baseline to week 4.
Mean change in patient global assessment (PGA) score from baseline to week 4.
4 weeks.
The Safety endpoints of the study are:
Proportion of subjects with adverse events (AEs) and serious adverse events.
Change in physical examination, vital signs, and clinical laboratory tests (hematology and biochemistry parameters) from baseline to week 4.
4 weeks.
Target Sample Size
Total Sample Size="990" Sample Size from India="990" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is
prospective,randomized,double-blind,vehicle-controlled.parellel group,
bioequivalence clinical trial to compare clinical efficacy, safety and tolerability
of generic Diclofenac Sodium Topical Gel 1%,with Voltaren® Gel (a
Diclofenac Sodium Topical Gel 1%) and Vehicle of Diclofenac Sodium Topical Gel
1% in approximately 23 centers. A minimum 990 subjects (330 in each treatment group) with osteoarthritis (OA) of the
knee.
Primary efficacy endpoint of the study is:
·Mean change in the
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain
score in target knee from baseline to week 4
The secondary efficacy endpoints of the study are:
·Mean change in pain
on movement (POM) on a Visual Analog Scale (VAS) for target knee from baseline
to week 4
·Mean change in patient global
assessment (PGA) score from baseline to week 4
The
Safety endpoints of the study are:
Proportion of subjects with adverse
events (AEs) and serious adverse events
Change in physical examination, vital signs, and
clinical laboratory tests (hematology and biochemistry parameters) from
baseline to week 4