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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Diclofenac sodium gel 1%
* Drug: Voltaren® Gel (Diclofenac Sodium Topical Gel) 1%
* Drug: Placebo gel


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |