E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
osteoarthritis of the knee |
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E.1.1.1 | Medical condition in easily understood language |
Osteoarthritis of the knee |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objectives of the study are to demonstrate clinical bioequivalence of Hi-Tech Pharmacal Co., Inc’s Diclofenac Sodium Topical Gel 1% compared to Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% (Novartis) in the treatment of patients with osteoarthritis of the knee. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ambulatory male and non-pregnant females 35 years and older diagnosed with osteoarthritis according to the American College of Rheumatology Criteria (ACR) (Appendix 2) in target knee. Target knee is the one with higher level of pain. ACR Criteria includes: Knee Pain and at least 3 of the following: 1) age ≥ 50 2) stiffness lasting < 30 mins 3) bony tenderness 4) crepitus 5) bony enlargement 6) no palpable warmth 2. Symptom onset of > 6 Months prior to Screening for the target knee. 3. If female and of child-bearing potential, prepare to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., IUD, oral, transdermal, injected, implanted hormonal contraceptives or condom + spermicide). 4. Periarticular knee pain due to osteoarthritis (not bursitis, tendonitis etc) that required the use of oral or topical treatments (e.g. NSAIDS or acetaminophen). 5. Radiograph of the target knee within the previous year with a Grade 1, 2 or 3 disease based upon the Kellgren-Lawrence disease severity scale (Appendix 3). 6. After a minimum of 7-day wash out of all pain medication has baseline pain on movement score of ≥ 50mm on a 0-100-mm Visual Analogue Scale for the target knee. 7. After a minimum of 7 day wash out of all pain medication has baseline WOMAC pain sub scale of ≥ 9 on a 5 question, 5 point (0 to 4) Likert scale for the target knee. 8. Willing and able to use only acetaminophen as rescue medication. 9. Willing and able to comply with the study requirements.
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E.4 | Principal exclusion criteria |
1. Females who are pregnant, breast feeding, or planning a pregnancy. 2. Radiograph of the target knee within the previous year with a Grade 4 score on the Kellgren-Lawrence disease severity scale (Appendix 3). 3. History of osteoarthritis in the contralateral knee requiring medication within 12 months of screening. 4. After a minimum of 7-day wash out of all pain medication has baseline pain on movement score of ≥ 20mm on a 0-100-mm Visual Analogue Scale for the contralateral knee immediately prior to randomization. 5. Known history of secondary osteoarthritis (e.g. congenital, traumatic, gouty arthritis) of the knee or rheumatoid arthritis. 6. Known history of other chronic inflammatory diseases, (e.g., colitis) or fibromyalgia during last 5 years. Patients whose disease was diagnosed at least 5 (five) years prior to screening visit and have had no known disease activity (i.e., no disease related complaints nor disease treatment prescribed) since then may enter into the study. 7. History of asthma, hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function or liver disease. Patients who have had high blood pressure measured at least 2 (two) years prior to screening visit and have had no disease activity (i.e., no record of hypertension nor anti-hypertensive treatment prescribed) for at least 2 (two) years prior to screening visit may enter into the study. 8. History of coronary artery bypass graft within 6 months of screening. 9. Concomitant acetylsalicylic acid therapy other than a stable low dose used for cardiac prophylaxis (max 162 mg daily) taken for at least 3 months prior to enrollment and maintained throughout the duration of the study. 10. Use of warfarin or other anticoagulant therapy within 30 days of screening. 11. Use of ACE inhibitors, cyclosporine, diuretics, lithium or methotrexate, within 30 days of screening or during the study. 12. Known history of gastrointestinal bleeding or peptic ulcer disease. 13. Abnormal screening clinical laboratory evaluations which the Investigator deems clinically significant. 14. Known allergy to aspirin or NSAIDs. 15. Skin lesions or wounds in the affected area. 16. Significant (requiring surgery) injury or major knee surgery to either knee within six months prior to screening. 17. Transaminase levels that are more than two times the upper limit of the normal range at screening. 18. Any other acute or chronic illness that in the opinion of the investigator could compromise the integrity of study data or place the Patient at risk by participating in the study. 19. Concomitant use of corticosteroids (any formulation) or use within 30 days of study randomization. 20. Receipt of any drug as part of a research study within 30 days prior to screening. 21. Previous randomization into this study. 22. Known allergy (hypersensitivity) to acetaminophen.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Mean Change from Baseline in WOMAC Pain Scale Time Frame: Baseline and Week 8 • Equivalence of Test and Reference Drug in the Mean Change from baseline in the WOMAC pain score. The analyses will be conducted in the Per-Protocol population using the WOMAC scores at Week 8.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at Week 8, Week 6 or Week 4 |
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E.5.2 | Secondary end point(s) |
• Superiority of Test and Reference against Placebo in the Mean Change from baseline in the total WOMAC pain score. Time Frame: Baseline and Week 8 The superiority of Test and Reference treatments over the placebo will be evaluated identically in Intent-to-Treat population using the WOMAC scores at Week 8, in separate ANCOVAs.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at Week 4, Week 6 or Week 8 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |