Rheumatoid Arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: AZD5672
Product Code: AZD5672
Pharmaceutical Form: Tablet
Current Sponsor code: AZD5672
Other descriptive name: AZD5672
Concentration type: equal
Concentration number: 20-
Pharmaceutical
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provision of informed consent (including PK subset consent, as applicable). 2.Male or female aged 18 or over. Note: Women of child-bearing potential may be included only if highly effective contraception is in place (see Section 3.3.4 and Appendix K) and patients are fully aware of the information relating to the potential for reprotoxicity as detailed in the informed consent form. 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. 3.Diagnosis of RA after the age of 16 according to the revised (1987) criteria of the American College of Rheumatology (see Appendix E). 4.Have active RA defined as: -³4 swollen joints and ³6 tender/painful joints and either: ESR =28 mm/h or, CRP =10 mg/L. 5.At least one of the following: -Documented history of positive rheumatoid factor -Current presence of rheumatoid factor -Baseline radiographic erosion -Presence of serum anti-cyclic citrullinated peptide antibodies (anti-CCP). 6.Oral or subcutaneous or intramuscular methotrexate for at least 6 months prior to randomisation. The dose and means of administering methotrexate must have been stable between 5 mg and 25 mg per week for at least 6 weeks prior to randomisation. 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 (see Appendix F) or wheelchair/bed-bound. 5.Patient unable to comply with the local approved product information for etanercept. Note: any patients randomised to receive etanercept will be confirmed as negative for LTBI prior to initiation of treatment. If the patient has had a negative TB test in the month prior to Visit 1, the result of that test will stand and the test does not need to be repeated. Patients who have a positive test result should be discontinued, see Section 3.3.5.1). Note: Where a local label is not available, then the label applicable to the supplied drug will apply. 6.Patients who have previously failed to respond to treatment with more than 1 biological agent. 7.Patients who in the opinion of the investigator have active TB as defined by clinical history and/or chest X-ray. 8.Patients who fail to comply with or are unlikely to stay compliant with the restrictions on prior and concomitant medication usage as provided in Section 3.7. 9.Clinical or biochemical evidence of active infection with hepatitis B or hepatitis C (carriers ie, those with positive serology but no evidence of active disease may be included). 10.Values of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or bilirubin >2 x upper limit of normal (ULN) at Visit 1. Note: If a potential patient has liver function only marginally outside these limits (as judged by the investigator), the patient may at the investigator’s discretion be brought back to study centre and retested not less than 2 weeks later and may be enrolled in the trial if the test(s) is then within the prescribed limit. 11.History of excessive alcohol consumption or chronic alcohol induced disease. 12.Patients who, in the opinion of the investigator, are at increased risk of ventricular arrhythmias, as suggested by (but not limited to): -QTc at enrolment >450 ms, persistent on 2 repeated ECG recordings 30 minutes apart (subject to cardiological review if clinical doubt over machine calculated value) -Other clinically significant ECG abnormality suggestive of clinically important underlying cardiovascular disease, including previous myocardial infarction; lack of sinus rhythm (ventricular ectopics allowed unless previously documented to be >100 per hour) -Personal or familial history of long QT syndrome -Personal history of clinical coronary heart disease (including angina) or congestive heart failure -Clinical history of non-sustained or sustained ventricular tachycardia -Visit 1 potassium outside normal range (subject to repeat if haemolysis etc, is suspected). Hypokalaemia may be treated if clinically indicated by potassium supplementation and patients may be included provided this is adequately corrected within the allowed screening period -Patients with a clinically significant left ventricular hypertrophy, as determined by ECG, ie, V1/2 + V5/6 =35 mm -Patients with brady-tachy syndrome that is not under satisfactory control -Patients who, in the opinion of the investigator, have a history of clinically significant valvular heart disease. 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the effect of AZD5672 (20, 50, 100 and 150 mg once daily) on the signs and symptoms of rheumatoid arthritis (RA) in patients on background methotrexate therapy, as measured by American College of Rheumatology 20% response criteria (ACR20) at 12 weeks. Both the treatment effect compared with placebo and the dose-response relationship will be evaluated.;Secondary Objective: 1.To further evaluate the effect of AZD5672 on the signs and symptoms of rheumatoid arthritis in patients on background methotrexate therapy· 2.To evaluate the safety and tolerability of AZD5672 in patients on background methotrexate therapy 3.To evaluate the effects of AZD5672 on physical function and quality of life (QoL) as measured by the HAQ (one of the ACR response criteria), individual dimensions of the HAQ, the SF-36 Questionnaire and the Rheumatoid Arthritis QoL Questionnaire (RAQoL) 4.To investigate the plasma pharmacokinetics (PK) of AZD5672 in the study population (to be reported separately) 5.To investigate possible relationships between systemic AZD5672 concentrations/exposures and adverse events (AEs), safety parameters and efficacy measurements (to be reported separately). ;Primary end point(s): The primary efficacy variable of this trial is the proportion of patients who achieve an ACR20 response at Week 12. | — |
Countries
Bulgaria, Czech Republic, Hungary, Italy, Latvia, Malta, Poland, Slovakia
Outcome results
None listed