A Bioequivalence Study Using Clinical Endpoint for Diclofenac Sodium Gel 1% in Osteoarthritis Knee"

A Randomized, Double Blind, Three-arm, Parallel, Placebocontrolled, Clinical Study to Evaluate the Bioequivalence Using Clinical Endpoint of Diclofenac Sodium Gel, 1% (Mylan Inc.) to Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% (Novartis Consumer Health, Inc.) in Patients With Osteoarthritis (OA) of the Knee

This randomized, double-blind, three-arm, placebo controlled, bioequivalence study with clinical endpoint has been designed to establish clinical equivalence and safety of Mylan's diclofenac gel in the symptomatic treatment of osteoarthritis of knee compared to Voltaren® gel and to establish superiority in efficacy of both compared to a placebo (vehicle) gel.

Male or non-pregnant female aged ≥ 35 years with a clinical diagnosis of osteoarthritis of the knee according to the American College of Rheumatology (ACR) criteria

Total study duration for the clinical part will be around 56 days that includes screening period of 28 days and treatment period of 4 weeks.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Drug: Diclofenac sodium gel 1%; Drug: Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%; Drug: Placebo gel

• Study Type: Interventional
• Enrollment (Actual): 1220
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500036
      • Yashoda Hospital - Malakpet
    • Secunderabad, Andhra Pradesh, India, 500003
      • Yashoda Hospital -Secunderabad
    • Somajiguda, Andhra Pradesh, India, 500082
      • Yashoda Hospital -Somajiguda
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • King George Hospital
  • Gujarat
    • Ahmedabad, Gujarat, India, 380008
      • Riddhi Medical Nursing Home
    • Ahmedabad, Gujarat, India, 380015
      • Rathi Hospital
    • Ahmedabad, Gujarat, India, 380015
      • Sanjivani Superspeciality Hospital Pvt. Ltd
    • Ahmedabad, Gujarat, India, 380016
      • B.J Medical College & Civil Hospital
    • Ahmedabad, Gujarat, India, 380061
      • GMERS Medical College & Civil Hospital
    • Baroda, Gujarat, India, 39000
      • SSG Hospital and Medical College
    • Himmatnagar, Gujarat, India, 383001
      • Medistar Multispeciality Hospital
    • Rajkot, Gujarat, India, 360005
      • Shree Giriraj Multispeciality Hospital
    • Vadodara, Gujarat, India, 390016
      • Anand Multispeciality Hospital
    • Vadodara, Gujarat, India, 391760
      • Parul Sevashram Hospital
  • Karnataka
    • Mangalore, Karnataka, India, 575002
      • Omega Hospital
    • Mysore, Karnataka, India, 570001
      • Mysore Medical College and Research Institute
  • Kerala
    • Ernakulam, Kerala, India, 683594
      • Sree Narayana Institute of Medical Science
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Sir J. J. Group of Hospital and Grant Government Hospital
    • Mumbai, Maharashtra, India, 400022
      • Lokmanya Tilak Municipal Medical College & General Hospital
    • Nagpur, Maharashtra, India, 440003
      • Government Medical College and Hospital
    • Nagpur, Maharashtra, India, 440012
      • Jasleen Hospital
    • Nagpur, Maharashtra, India, 600001
      • Institute of Medical sciences and Lata Mangeshkar
    • Nashik, Maharashtra, India, 422002
      • Supe Heart and Diabetes Hospital & Research Centre
    • Pune, Maharashtra, India, 411001
      • BJ medical college & Sassoon General Hospital
    • Pune, Maharashtra, India, 411005
      • Sancheti Institute for Orthopedics & Rehabilitation
    • Thane, Maharashtra, India, 401107
      • Bhaktivedanta Hospital and Research Institute
  • Odisha
    • Bhubaneshwar, Odisha, India, 751003
      • IMS and SUM Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600001
      • Govt Stanley Medical College & Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226003
      • M.V. Hospital & Research Centre
    • Lucknow, Uttar Pradesh, India, 226005
      • Ajanta Research Centre
    • Varanasi, Uttar Pradesh, India, 221007
      • OM surgical Centre and Maternity Home
  • West Bengal
    • Kolkata, West Bengal, India, 700020
      • Institute of Post Graduate Medical Education and Research (IPGMER), Department of Orthopaedics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 33 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Osteoarthritis knee as per American College of Rheumatology (ACR) criteria
• Evidence of OA with Kellgren-Lawrence grade 1-3 disease.
• After discontinuing all pain medications, had at least moderate pain on movement (POM) for target knee
• After discontinuing all pain medications 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.
• Able to tolerate rescue medication with acetaminophen
• Subjects who can read and understand WOMAC pain sub scale

Exclusion Criteria:

• Pregnancy, lactation
• OA of Kellgren-Lawrence grade 4
• OA pain in the contralateral knee requiring medication (OTC or prescription)
• History of OA of either Hip or Hands
• History of secondary OA (e.g. congenital, traumatic, gouty arthritis), rheumatoid arthritis
• History of chronic inflammatory disease (e.g., colitis) or fibromyalgia
• History of Drugs or Alcohol abuse within the previous year
• Symptomatic peripheral vascular disease of the study leg
• Any musculoskeletal condition
• Skin disease at the application site
• Active asthma requiring periodic treatment with systemic steroids
• Known history of positive HIV, hepatitis C virus, or HBsAg
• Uncontrolled hypertension
• History of myocardial infarction, thrombotic events, stroke etc.
• Allergy to aspirin, nonsteroidal anti-inflammatory drugs (NSAID) or acetaminophen (paracetamol).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diclofenac Sodium Gel; Diclofenac Sodium Gel, 1%	Drug: Diclofenac sodium gel 1%; Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks
Active Comparator: Voltaren® Gel; Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%	Drug: Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%; Diclofenac Sodium Topical Gel, 1%. 4 gm, 4 times a day for 4 weeks
Placebo Comparator: Placebo gel	Drug: Placebo gel; Vehicle Gel 4 gm, 4 times a day for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in the Total WOMAC Pain Subscale Score	Mean change in the total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain subscale score for the target knee was compared 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.) Measure Description: Western Ontario and McMaster Universities Osteoarthritis Index WOMAC pain subscale score (pain score = min 0 to max 20), was determined by the sum of subject's responses to five questions (S1-S5) using a 5-point Likert scale (i.e., 'none'=0; 'mild'=1, 'moderate'=2; 'severe'=3; 'extreme'=4). Higher values represent worse outcome. 'How much pain do you have' when 'Walking on a flat surface' (S1), 'Going up or down stairs' (S2), 'at night while in bed' (S3), 'Sitting or lying' (S4), 'Standing upright' (S5)]. The timepoints considered for the primary outcomes include baseline and week 4.	From baseline to week 4
Change From Baseline in WOMAC Pain Subscale Score	Mean change in the total WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain subscale score for the target knee was compared to determine the superiority of the Test Drug and Reference Listed Drug (RLD) over placebo. Measure Description: Western Ontario and McMaster Universities Osteoarthritis Index WOMAC pain subscale score (pain score = min 0 to max 20), was determined by the sum of subject's responses to five questions (S1-S5) using a 5-point Likert scale (i.e., 'none'=0; 'mild'=1, 'moderate'=2; 'severe'=3; 'extreme'=4). Higher values represent worse outcome. 'How much pain do you have' when 'Walking on a flat surface' (S1), 'Going up or down stairs' (S2), 'at night while in bed' (S3), 'Sitting or lying' (S4), 'Standing upright' (S5)]. The timepoints considered for the primary outcomes include baseline and week 4.	4 weeks

Collaborators and Investigators

• Sponsor: Mylan Pharmaceuticals Private Limited

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2017
• Primary Completion (Actual): December 5, 2017
• Study Completion (Actual): December 5, 2017

Study Registration Dates

• First Submitted: May 30, 2017
• First Submitted That Met QC Criteria: May 30, 2017
• First Posted (Actual): June 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: MYL-1601N-3002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes