Rheumatoid Arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: AZD9056 hydrochloride
Product Code: AZD9056
Pharmaceutical Form: Tablet
Current Sponsor code: AZD9056
Other descriptive name: None
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent 2. Male or female, aged 18 years or over 3. Females must be using 2 forms of contraception for the duration of the study and 4 weeks after the last dose of study medication, unless they are surgically sterile or post-menopausal. Males who are involved in the study must agree to abstain from procreative sex during the study and for 12 weeks after the last dose of study medication 4. Diagnosis of RA after the age of 16 according to the revised (1987) criteria of the American College of Rheumatology 5. Have active RA defined as: =4 swollen joints and =6 tender/painful joints (from 28 joint count) and either: - ESR =28 mm/h - CRP =10 mg/L. 6. At least one of the following: - Documented history of positive rheumatoid factor - Current presence of rheumatoid factor - Baseline radiographic erosion - Presence of serum anti-CCP antibodies. 7. Be receiving one of the following treatments: - Oral, subcutaneous or intramuscular methotrexate for at least 6 months prior to randomisation. - Oral sulphasalazine for at least 16 weeks prior to randomisation. 8. Haemoglobin at Visit 1 either: - within the normal range, or - below the normal range but not less than 9 g/dl and only if normochromic and normocytic with no clinical or laboratory signs of chronic blood loss. 9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =1.2 x upper limit of normal (ULN) at Visit 1; bilirubin equal to or below the upper limit of normal at Visit 1. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating females 2. Any systemic inflammatory condition in addition to RA that may interfere with the interpretation of the outcome data (examples include but are not limited to polymyalgia rheumatica, giant cell [including temporal] arteritis, reactive arthritis) 3. Current chronic pain disorders including fibromyalgia and chronic fatigue syndromes 4. American College of Rheumatology functional class IV or wheelchair/bed-bound 5. Persistently abnormal liver function enzymes defined as AST/ALT >2 x ULN on more than one occasion in the past 6 months; or any pattern of liver function test abnormality in the previous 6 months requiring specific investigation 6. Treatment with any of the following: - Leflunomide, cyclosporine, azathioprine or hydroxychloroquine within 28 days of randomisation. Note: Any patient that has received leflunomide less than 3 months but more than 4 weeks before randomisation must have completed a cholestyramine washout prior to study entry - Biological agents and anti-TNF agents within 56 days (with the exception of rituximab, which must not have been used within 12 months) of randomisation - Gold within 12 months of randomisation. 7. Any prior treatment with etanercept 8. Patients for whom etanercept is inappropriate including: - Hypersensitivity to the active substance or to any of the excipients - Sepsis or risk of sepsis - Patients with active infections (including chronic or localised infections) - Patients being treated with anakinra. Note: Physicians should exercise caution in patients with a history of recurring or chronic infections or with underlying conditions that may predispose patients to infections (such as advanced or poorly controlled diabetes). - Patients who have received live vaccine in the 4 weeks prior to randomisation - Patients who have a previous history of blood dyscrasias - Patients with pre-existing or recent onset of CNS demyelinating disease, or to those who are considered to have an increased risk of developing demyelinating disease - Patients who have congestive heart failure - Patients with Wegener's Granulomatosis. 9. Patients with a history of active tuberculosis or who have a positive tuberculin skin test or chest X-ray findings suggestive of active or healed tuberculosis (other than calcified foci alone). 10. Intramuscular or intravenous steroid injection or intra-articular steroid injection within 6 weeks of randomisation 11. Patients receiving any of the following: - Lovastatin - Doses of simvastatin and atorvastatin >20 mg per day - Moderate to strong CYP3A4 inhibitors/substrates 12. Patients receiving digoxin or cisapride 13. Patients with known Human Immunodeficiency Virus (HIV) or belong to a high risk group for HIV infection 14. Evidence of serum hepatitis or presence of hepatitis B surface antigen or hepatitis C antibodies 15. History of malignancy or neoplastic disease, except successfully treated basal or squamous cell carcinoma of the skin 16. Chronic liver (also consider inclusion criterion 9 and exclusion criterion 5) or renal disease (subjects may be included if the plasma/serum creatinine is within the normal range or if abnormal the calculated (using Cockroft-Gault) or measured glomerular filtration rate (GFR) must be > 50 mL/min) 17. Patients with current active peptic ulceration or a history of peptic ulcer disease in the previous 5 years 18. Any other clinically significant disease or disorder, which in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the dose response relationship across 4 doses of AZD9056 (50, 100, 200 and 400 mg) on signs and symptoms of rheumatoid arthritis (RA), as measured by the proportion of patients meeting the American College of Rheumatology 20% response criteria (ACR20) at 6 months.;Secondary Objective: (1) To evaluate the dose response relationship across 4 doses of AZD9056 on signs and symptoms and disease activity of RA (2) To investigate AZD9056 population pharmacokinetics in plasma in patients with RA (3) To evaluate the safety and tolerability of AZD9056 (4) To provide information on the effects of AZD9056 on the quality of life measured by Short-Form-36 (SF-36) and Rheumatoid Arthritis Quality of Life (RAQoL) Questionnaire (5) To investigate radiological changes using standard X-ray (using the Sharp score as modified according to the method of van der Heijde). ;Primary end point(s): The primary efficacy variable of this trial is the proportion of treated patients who achieve ACR20 at Visit 8. The proportion of patients who achieved ACR20 will be computed at Visits 3 to 9. Visit 8 (computed on the full analysis set) will be regarded as the primary endpoint. | — |
Countries
Belgium, Czech Republic, France, Poland, Sweden
Outcome results
None listed