Proof-of Concept Study of Topical 3%-Diclofenac-Nano-Emulsion Cream for Knee OA Pain

This will be a multi-center, double-blind, placebo-controlled, multiple-dose, parallel treatment study. A total of 126 subjects will be randomized to receive either 3%-Diclofenac-NE cream or a placebo cream respectively. Following screening and a washout period from previous treatments subjects will be enrolled and will self-apply the study medication. During the study, subjects will apply 3%-Diclofenac-NE or placebo cream three times daily for 28 days and complete a home-diary. Subjects will visit the clinic at mid-treatment for a follow up examination and again for a final examination at the end of treatment.

Inclusion criteria

• Males and females 50 years of age and above.
• Patients with primary osteoarthritis in at least a single knee joint, grade 2 or 3 based on the Kellgren and Lawrence classification system.
• Radiographic evidence consistent with OA carried out within the 6 months before screening.
• Pain should have been present for at least half of the days in the previous month and for at least 48h prior to the screening visit.
• Eligible subjects must have used an oral, topical or rectal NSAID within the past 6 months before screening.
• At baseline, after a 1 week withdrawal period of analgesic/anti-inflammatory medications, subjects should have a flare of pain.
• Able to read, comprehend, and sign the consent form.
• Examined by the authorized physician and medically cleared to participate in the study.
• In general good health and have no contraindications to any of the investigational medicinal products.

Exclusion criteria

• Secondary osteoarthritis.
• Presence of a serious or unstable medical condition (e.g., malignancy, severe neurological impairment or uncontrolled hypertension) or poor general health interfering with compliance or assessment at the study physician's discretion.
• OA causing significant pain in any joint other than the knees.
• Any other rheumatic or non-rheumatic joint disease or any other painful condition within the past month (e.g. fibromyalgia).
• Knee surgery or other knee trauma at any time during the previous year or subjects for whom a treatment is planned within the study period that could alter the degree or nature of pain (e.g. arthroscopic techniques, osteotomy, joint replacement surgery etc.).
• Active or history of gastrointestinal ulceration or bleeding within the past 5 years.
• Presence of a significant active psychiatric disorder including major depression or subjects receiving anti-psychotic medication.
• Existence of any dermatological condition on the knee.
• Subjects with disabling congestive heart failure (CHF), angina, pulmonary disease.
• Clinically significant abnormal blood results.
• Subjects cannot have had an arthrocentesis prior or during the study.
• Concomitant treatment with physical and/or occupational therapy.
• Prior use of any type of NSAID or other analgesic before taking the first dose of investigational medicinal product. Rescue treatment will be allowed during the study
• Change in sedative or CNS/psychotropic agent within the past month.
• Chronic treatment with anticoagulants (e.g. Warfarin).
• Subjects under treatment with corticosteroids.
• Subjects using topical analgesics including OTC products.
• Females who are pregnant, lactating, of child-bearing potential, or post-menopausal for less than 2 years and not using a medically approved method of contraception (i.e., oral, transdermal, or implanted contraceptives, intrauterine device, diaphragm, condom, abstinence, or surgical sterility), or females who test positive on a urine-based pregnancy test.
• Active alcoholism or substance abuse.
• Has taken an investigational drug or has used an investigational device within the past 30 days.
• History of hypersensitivity and/or idiosyncrasy to diclofenac or excipients employed in this study, aspirin or other NSAIDS.
• Has previously been entered into this study.
• Any condition that in the investigator's judgement precludes participation in the study.