E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of osteoarthritis of the knee |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031161 |
E.1.2 | Term | Osteoarthritis |
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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 |
To evaluate the efficacy of two dosages of Diractin® (50 mg, 100 mg ketoprofen in Transfersome® gel) in patients with mild to moderate pain related to osteoarthritis (OA) of the knee. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the overall safety of two dosages of Diractin® (50 mg, 100 mg ketoprofen in Transfersome® gel) in patients with mild to moderate pain related to OA of the knee. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Informed consent signed and dated • Age older than 45 years (if age of 18-45, radiological confirmation of diagnosis of knee OA is required) • Subject has a primary diagnosis of Functional Class I-III OA of the knee and subject meets American College of Rheumatology (ACR) clinical classification criteria for osteoarthritis of the knee, defined by the following:
Knee pain and at least 4 of the following 6: o Age >50 o Morning stiffness <30 minutes o Crepitus on active motion o Bony tenderness o Bony enlargement o No palpable warmth of synovium • Patient able to identify a predominantly painful (index) knee • Mild to moderate pain defined by pain on walking on a flat surface of the index knee defined by question 1 of the WOMAC rated ≥ 4 and a total average WOMAC pain subscale of < 7 at B1 and B2 • If female, subject is either not of childbearing potential (defined as postmenopausal for at least one year or surgically sterile [bilateral tubal ligation, bilateral oophorectomy or hysterectomy]) or subject is of childbearing potential and practicing one of the following methods of birth control: o total abstinence from sexual intercourse (minimum one complete menstrual cycle before study entry), o a vasectomized partner, o contraceptives (oral, parenteral, or transdermal) for three consecutive months prior to investigational product administration, o intrauterine device (IUD), or o double-barrier method (condoms, sponge, diaphragm or vaginal ring with jellies or cream). • If female of childbearing potential, subject has a negative urine pregnancy test at screening and B2.
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E.4 | Principal exclusion criteria |
• Difference in WOMAC pain rating for question 1 or the total average pain score between B1 and B2 > 2 • Skin lesions or dermatological diseases in the treatment area • Extreme obesity (BMI > 37) • Directly or indirectly involved in the conduct and administration of this study (i.e. principal investigator, sub-investigator, study co-ordinators, other study staff, employees of IDEA AG, IDEA contractors and/or their families) • Received any investigational medicinal product within 30 days prior to Screening Visit or participation in any previous clinical study with Diractin® • Pregnancy or lactation • Residents of psychiatric wards, prisons or other state institutions
• Malignancy within the past 2 years • Morbus Meulengracht/Gilbert syndrome • Depressive Disorders requiring treatment with tricyclics, treatment with other antidepressants must be stable for 3 months prior to screening and throughout the study • Epilepsy • Schizophrenia • Neuropathic pain and any other pain condition requiring chronic use of pain medication • Known hypersensitivity or allergy (including photoallergy) to NSAID´s including ketoprofen, celecoxib, sulfonamides, omeprazole, paracetamol and to ingredients of the IMP including galactose • Preexisting asthma bronchiale or bronchospasm after taking aspirin or other NSAIDs • Inflammatory arthritis including rheumatoid arthritis, psoriatic arthritis, gout of the index knee, pseudogout, systemic lupus erythematodes, or mixed connective tissue disease • Symptomatic ipsilateral hip OA or predominant retropatellar knee OA • Coagulopathy or bleeding diathesis, or concomitant use of anticoagulants including low dose aspirin • Ischemic heart disease requiring drug therapy • Peripheral arterial disease and/or cerebrovascular disease • History of stroke or myocardial infarction • Congestive heart failure NYHA Class II-IV • History of pancreatitis or peptic ulcers • Inflammatory GI disease (e.g. M. Crohn, colitis ulcerosa) • Serum creatinine levels > 2.5 milligrams/deciliter (mg/dL) • ALT or AST ≥ 5 times the ULN
• Within 3 months prior or during the study o Intraarticular injections of hyaluronic acid products in the index knee o Arthroscopy of the index knee o Tricyclics • Within 2 months prior or during the study o Oral, inhaled or parenteral corticosteroids (depot steroids 6 months) o Change in oral treatment regimen of glucosamine, chondroitin sulfate, shark cartilage, methylensulfonylmethan (MSM), Vitamin E, diacerin or nutraceuticals • Within 1 month prior or during the study o Intraarticular injections of corticosteroids in the index knee within 1 months prior to screening or during the study o Antiepileptic drugs o Acupuncture or physical therapy of the index knee including ice/heat packs and massage • Unable to discontinue therapy with proton-pump inhibitors, H2 inhibitors and analgesic therapy including opioids, NSAID´s, tramadol, muscle relaxants, gabapentin, pregabalin, duloxetine, venlafaxine, capsaicine or any other drug approved or used for the treatment of pain for the duration of the study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is: • Change from baseline at Week 12 on the entire pain subscale of the WOMAC (NRS)
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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.8.3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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The end of study is defined by closure of database for CL-033-III-03. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |