Osteoarthritis of the knee MedDRA version: 9.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis MedDRA version: 9.1 Level: LLT Classification code 10031165 Term: Osteoarthritis knee
Conditions
Interventions
Product Code: AZD1386 30 mg
Pharmaceutical Form: Capsule, hard
Current Sponsor code: AZD1386 hydrogen sulphate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
P
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures. 2. Patients with OA of the knee that have unsatisfactory pain relief from past or on going nsNSAIDs/COX-2s and paracetamol/acetaminophen treatment either consecutively or simultaneously at recommended doses for at least 2 weeks, or with intolerability to past or on-going nsNSAIDs/COX-2s irrespective of doses, or dosing period, as judged by the investigator. Patients that have intolerability to NSAIDs/Cox-2s must have tried acetaminophen/paracetamol for at least 2 weeks at any time with unsatisfactory pain relief. 3. WOMAC pain on walking must be =40 mm and =90 mm VAS on both enrolment V1 and randomisation V2. 4. Male, or non-pregnant females, =40 and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A current diagnosis of another form of arthritis, in addition to OA (e.g. rheumatoid arthritis, gout, septic arthritis, juvenile arthritis and lupus erythematosus) or wide spread chronic pain or fibromyalgia. 2. Patients with intra-articular or intramuscular corticosteroids or intra-articular hyaluronic acid injections within 3 months prior to randomisation. 3. Oral use of corticosteroids, barbiturates, rifampicin or phenytoin within 6 weeks prior to the randomisation visit. 4. Analgesic treatment, except low dose aspirin up to 325 mg/day for cerebrovascular and cardiovascular profylaxis. 5. Concomitant use of strong and moderate CYP3A4 enzyme inhibitors, such as ketoconazole, itraconazole, clarithromycin, nefazodone, erythromycin, fluconazole, aprepitant, diltiazem, verapamil, grapefruit juice, HIV protease inhibitors. 6. Within the last month prior the enrolment visit using >4 gram/ day (Japan: >1.5 gram/ day) of paracetamol/acetaminophen. 7. Within the last month prior the enrolment visit using more than the highest recommended dose of any NSAIDs or COX-2 inhibitors. 8. History, and/or presence, of somatic disease/condition, which may interfere with the objectives of the study as judged by the investigator. 9. Malabsorption, gastrointestinal disorder or surgery leading to impaired drug absorption. 10. History of malignancy, treated or untreated, within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin. 11. Risk factors for ventricular fibrillation e.g. family history of Short QT syndrome (SQTS) or sudden cardiac death (SCD) amongst first-degree relatives. 12. QTcF interval 450 msec at enrolment. 13. A recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence, including overuse/abuse of narcotics for management of pain. 14. Enrolment laboratory value for ALT, AST >2 times the upper limit of normal range. 15. Known positive test result for human immunodeficiency virus (HIV) antibody, hepatitis B surfactant antigen (HbsAg) or hepatitis C antibody. 16. Clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator. 17. Breast-feeding women. 18. Positive pregnancy test. 19. Donation of plasma within the two weeks prior to the enrolment visit and/or donation of blood within the three months prior to the enrolment visit and during the study. 20. History of allergic reaction to paracetamol/acetaminophen. 21. Involvement in the planning and conduct of the study (applies to both AZ staff and the staff at the study site). 22. Participation in another clinical trial, use of any investigational drugs or procedures or use of experimental medications within 30 days prior to the enrolment visit. 23. According to the investigator the patient should not participate in the study. In addition, the following criteria are regarded as criteria for exclusion from the genetic research: 24. Previous bone marrow or stem cell transplant. 25. Whole blood transfusion within 120 days of the date of genetic sample collection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are to evaluate the relationship between dose and analgesic efficacy of AZD1386 and evaluate the analgesic efficacy of AZD1386 in patients with osteoarthritis of the knee. The dependent variables will be mean of change from baseline to Week 2 (V4) and Week 4 (V5) in WOMAC pain subscale, 48 hours recall.;Secondary Objective: 1. To evaluate the analgesic efficacy of AZD1386 during the night and day, in patients with osteoarthritis of the knee. 2. To evaluate the efficacy regarding function and stiffness and relationship between dose and efficacy of AZD1386 in patients with osteoarthritis of the knee. 3. To evaluate the percentage responders for AZD1386. 4. To investigate the safety and tolerability of AZD1386. 5. To evaluate the difference in use of rescue medication (paracetamol/acetaminophen) between AZD1386 and placebo. ;Primary end point(s): Efficacy Primary outcome variable: - Change from baseline over time in WOMAC pain subscale, 48 hours recall. Safety - Change from baseline in physical examination, laboratory values, vital signs (blood pressure [BP], pulse rate and body temperature) and electrocardiogram (ECG) including QTcF. - Adverse Events (AEs) including frequency and severity. - AEs leading to withdrawals. | — |
Countries
Bulgaria, Finland, Hungary
Outcome results
None listed