Comparison of the Efficacy of Diclofenac Sodium Topical Gel, 1% (Mylan) to Voltaren® Gel, 1% (Novartis US) and Placebo in Adult Subjects with Knee Osteoarthritis
- Conditions
- Osteoarthritis of joints amenable to topical treatment, such as the knees.MedDRA version: 14.1Level: LLTClassification code 10023476Term: Knee osteoarthritisSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2012-002682-36-HU
- Lead Sponsor
- Mylan Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1600
- Male and Female subjects aged 35 years or older with a clinical diagnosis of
osteoarthritis of the knee according to the American College of Rheumatology (ACR)
criteria:
1. knee pain plus 3 of the following:
a. 50 years of age or older
b. stiffness lasting less than 30 minutes,
c. crepitus,
d. bony tenderness,
e. bony enlargement,
f. no warmth to the touch,
and including:
2. Symptoms for at least 6 months prior to screening; AND
3. Knee pain (not referred) for at least 15 days of the preceding month (30 days)
(periarticular knee pain due to osteoarthritis and not due to other conditions such
as bursitis, tendonitis, etc); AND
4. the pain in the target knee required the daily use of non-steroidal antiinflammatory
drugs (NSAIDS) or acetaminophen/paracetamol (topical or oral
treatments);
5. Had an X-ray of the target knee, taken no more than 1 year before the initiation of
the study, demonstrating evidence of osteoarthritis with Kellgren-Lawrence grade
1-3 disease;
6. After discontinuing their current regimen of analgesic(s) for a period of at least 7 days or = 5 half-lives of the mean half-life of their previous analgesic, which ever is longer,had at least moderate pain on movement (POM) in the target knee, defined as a baseline score of = 50 mm on a 0-100 mm Visual Analog Scale (VAS) immediately prior to randomization, AND a baseline Western Ontario McMaster Osteoarthritis (WOMAC®) pain subscale of at least 9 immediately prior to randomization; and
7. Willing to use and able to tolerate the rescue medication
(acetaminophen/paracetamol)
- Males and non-pregnant, non-lactating females weighing at least 50 kg and 48 kg,
respectively
- Subjects judged by Principal Investigator or Medical Sub-investigator as otherwise
normal and healthy during a pre-study medical evaluation including physical
examination, vital signs (respiration rate, blood pressure, temperature, and heart rate),
within normal limits or not clinically significant laboratory results for serum
chemistries, hematology and urinalysis.
- Negative Hepatitis B, Hepatitis C, and HIV test
- Negative urine drugs of abuse screen
- Normal or not clinically significant electrocardiogram (EKG/ECG).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400
1. Institutionalized subjects will not be used.
2. History of drug and/or alcohol abuse.
3. Women who are pregnant, lactating, or planning to become pregnant during the
study period.ALT (SGPT) and AST (SGOT) values higher than 3.0 times the upper limit of normal.
4. Social Habits:
a. Alcohol consumption greater than 15 units of alcohol per week with 1 unit equivalent to 12 oz of beer (350 mL), 4 oz of wine (120 mL), or 1.5 oz (45mL) of 80 proof (40% alcohol) distilled spirits,
b. Caffeine ingestion greater than 5 cups (180 mL/cup) of coffee or its equivalent of caffeine- or xanthine-containing foods or beverages per day.
c. Ingestion of any vitamin or herbal supplement known to induce or inhibit hepatic enzyme activity within 7 days prior to the initial dose of study medication. (see Sec 18. Hepatic Enzyme Inducers and Inhibitors List).
d. Any recent, significant change in dietary or exercise habits.
5. Medications:
a. All concomitant medications will be documented. Individuals receiving
medications with clinically significant drug-drug interactions with diclofenac
or other non-steroidal anti-inflammatory drugs (NSAIDs) will be excluded
unless the drug can be safely discontinued.
b. Use of anticoagulants, ACE-inhibitors, cyclosporine, tacrolimus, sirolimus, diuretics, lithium, methotrexate within 30 days prior to the first dose of study medication. Stable doses of ACE-inhibitors and diuretics will be allowed if taken for at least 3 months prior to enrollment and maintained throughout the study.
c. Use of intra-articular hyaluronic acid injections with in 6 months of study start.
d. Use of pain medication (e.g. NSAIDs, opioids, muscle relaxants) within the last 7 days prior to the first dose of study medication.
e. Use of acetaminophen (paracetamol) during the 24 hours prior to the
randomization visit.
f. Use of aspirin (acetylsalicylic acid) therapy other than a stable low dose used for cardiac prophylaxis (= 162 mg/day) taken for at least 3 months prior to enrollment and maintained throughout the duration of the study.
g. Use of glucosamine, chondroitin, systemic or topical corticosteroids within 30 days of the first dose of study medication.
h. Diacerein (also known as Diacetylrhein), and ASU (Avocado-Soybean
Unsaponificable) within 30 days of the first dose of study medication.
i. Use of occlusive bandages, ultrasound, transcutaneous electrical stimulation or any alternative therapies such as acupuncture, homeopathy, or mesotherapy for the treatment of osteoarthritis within 7 days of the first dose of study medication.
j. Use of any medication known to induce or inhibit hepatic enzyme activity
within 30 days prior to the first dose of study medication except for those agents expressly allowed. (see Sec 18. Hepatic Enzyme and Inhibitors List).
6. Diseases:
a. History of osteoarthritic (OA) pain in the contralateral knee requiring
medication within 1 year prior to screening.
b. After discontinuing all pain medication for at least 7 days, had a baseline score
of = 20 mm on 0-100 mm Visual Analog Scale (VAS) for POM in the
contralateral knee immediately prior to randomization.
c. History of secondary osteoarthritis (e.g. congenital, traumatic, gouty arthritis),
rheumatoid arthritis, chronic inflammatory disease (e.g. colitis) or
fibromyalgia.
d. History of gastrointestinal bleeding or peptic ulcer disease.
e. X-ray showing evidence of osteoarthritis with Kellgren-Lawrence grade 4 disease.
f. History of any significant or unstable card
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objective of this study is to investigate the clinical endpoint bioequivalence of<br>Mylan's Diclofenac Sodium Topical Gel, 1% compared to Novartis US’ Voltaren® Gel,<br>1% and placebo (vehicle, Mylan) following multiple topical applications of 4 g to a<br>single osteoarthritic knee (4 g four times daily for 4 weeks).;Secondary Objective: No secondary objectives of the trial have been established.;Primary end point(s): The primary bioequivalence endpoint will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) pain<br>score.;Timepoint(s) of evaluation of this end point: Visit number 6.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): No secondary endpoints have beed established.;Timepoint(s) of evaluation of this end point: N/A