Rheumatoid arthritis MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Name: AK106-001616
Pharmaceutical Form: Capsule, hard
CAS Number: 590416-75-4
Current Sponsor code: AK106-001616 (form B)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentr
Sponsors
Asahi Kasei Pharma Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosed as having adult-onset RA (defined by the 1987 American College of Rheumatology [ACR] classification criteria) for duration of at least 3 months. 2. Functional Capacity Classification of I-III (detailed in Appendix F). 3. Aged between 18 and 65 years inclusive. 4. Has been stable on MTX therapy (5 to 25 mg administered as a single weekly dose) for at least 12 weeks. 5. Women of childbearing potential must confirm use of adequate contraception since last menses, must confirm continued use of adequate contraception during the study, must have a negative urine pregnancy test before administration of study drug and must be willing to use adequate contraception for 3 months from the end of the study. Adequate contraception is defined as the use of two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide). A condom alone is not considered an acceptable method of birth control. 6. Male patients with a female partner of childbearing potential must be willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) during the study and for 3 months following administration of the study drug. 7. Patients must have a negative urine screen for drugs of abuse. 8. Patients must have negative screening for hepatitis B (hepatitis B surface antigen [HBsAg] negative) and hepatitis C (negative anti-hepatitis c virus [HCV]). 9. Must be able to communicate well with the investigator, to understand and comply with the requirements of the study, and be judged suitable for the study in the opinion of the investigator. 10. Able to give voluntary written informed consent to participate in this trial. Part 1 only: If the subject has been using non-steroidal anti-inflammatory drugs (NSAIDs) prior to this study they must be on a stable NSAID therapy and have a Functional Capacity Classification (detailed in Appendix F) that has not changed for at least 4 weeks. Part 2 only: Patient has RA activity at screening and baseline (Day 1, pre-morning dose), defined as a disease activity score (DAS28) score of = 3.2, and a change in DAS28 score from screening to baseline that is > 0 and = 1.2 (baseline – screening). Additional criterion for inclusion in the sub-group of patients who have their synovial fluid sampled: Aspiration of synovial fluid from the knee joint is clinically indicated in the opinion of the investigator. 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects will be excluded from participation in the study if any of the following criteria are met at screening and at baseline: 1. Has been diagnosed with a secondary, non-inflammatory type of arthritis (e.g., osteoarthritis or fibromyalgia) that might interfere with the evaluation of the effect of study medication on RA symptoms. 2. Pregnant or breastfeeding. 3. Taken any NSAID (including aspirin) within at least 5 times the half-life of the NSAID (at least 2 days) before the baseline visit or any analgesic within 24 hours before the baseline visit. In Part 2 only, patients taking = 150 mg aspirin per day for non-arthritis reasons for at least 30 days before the first dose of study medication will be permitted to enter the study and will be allowed to continue their aspirin regimen for the duration of the study. 4. Taken any anti-ulcer drugs (i.e., H2 blockers, proton pump inhibitors, etc) during the time of NSAID washout. 5. Treated with: - Anti-tumour necrosis factor (TNF) drugs or other biologicals (except rituximab) e.g. anakinra, abatacept, in the past 3 months. - Rituximab in the past 6 months. 6. Has begun taking any of the following medications or has changed the dosing regimen of any of these medications within 12 weeks before receiving the first dose of study medication: - Gold salts (including oral gold); - Sulfasalazine; - MTX; - Azathioprine; - Antimalarials; - Penicillamine; - Combination therapies used in RA treatment; - Leflunomide. 7. Has begun taking oral corticosteroids or changed the dose regimen of oral corticosteroids within 4 weeks before receiving the first dose of study medication (doses of up to 10 mg prednisone or equivalent per day are allowed), or the patient has received intramuscular, intra articular or soft-tissue injections of corticosteroids within 8 weeks before receiving the first dose of study medication. 8. Received any antineoplastic (other than MTX = 25 mg/week or azathioprine as therapy for RA) during the 8 weeks preceding the first dose of study medication. 9. Has an active malignancy of any type or a history of malignancy (with the exception of patients who have been in remission for at least 5 years and patients who have a history of treated basal cell carcinoma and carcinoma in situ of the cervix). 10. (a) Has a history of 2 or more types of active peptic ulceration as below: - GI bleeding; - Recurrent gastric ulcers; - Duodenal ulcers. (b) Has an oesophageal, gastric or duodenal ulcer within 30 days before the first dose of study medication; (c) Has active GI disease or any condition precluding NSAID therapy. 11. Has clinically significant chronic/acute hepatic or renal disorder or a significant coagulation defect. 12. Has: - An abnormal screening laboratory test value that is considered by the investigator to be clinically significant, or; - A value that is > 2 times the upper limit of normal (ULN) for aspartate aminotransferase (AST) or alanine aminotransferase (ALT), or; - A value for serum creatinine > 1.5 times the ULN at screening, or; - An absolute neutrophil count (ANC) < 1500/mm3 (or white blood cell count [WBC] < 3 x 109/L), haemoglobin < 8 g/dL or platelets < 100 x 109/L. 13. Has a known hypersensitivity to paracetamol and/or NSAIDs. 14. Has received any investigational medication within 90 days before the first dose of study medication. 15. Has previously been admitted to this study. 16. Has a current uncontrolled medical disorder (myocardial infarction, unstable angina, u
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: - To assess the effect of multiple, oral, ascending doses of AK106 001616 on the plasma and urine concentrations of methotrexate (MTX) and its metabolite, 7 hydroxy MTX, when administered to patients with rheumatoid arthritis (RA). Part 2: - To compare the urine PD effects of multiple, oral doses of AK106 001616 with those of a comparator drug in patients with RA. - To compare the safety and clinical efficacy of AK106 001616 in patients with rheumatoid arthritis to that of a comparator. ;Secondary Objective: Part 1: - To assess the pharmacokinetics (PK) of AK106-001616 and its active metabolite AK106-001640, when administered to RA patients who are taking methotrexate (MTX). - To assess the urine pharmacodynamic (PD) effects, safety and clinical efficacy of AK106-001616, in comparison to placebo, when administered to RA patients who are taking MTX. Part 2: - To assess the correlation between the clinical efficacy and PD effects of AK106 001616 when administered to patients with RA. - To assess the PK of AK106-001616 and its active metabolite AK106 001640 when administered to patients with RA. - To compare the PD effects of AK106 001616 in synovial fluid to those of a comparator in a subpopulation of the RA patients studied (optional). - To compare the effect of AK106 001616 on gastrointestinal (GI) damage to that of a comparator in a subpopulation of the RA patients studied (optional).;Primary end point(s): Pharmacodynamic endpoints: Part 1: - Urine LTE4/urine creatinine - Urine PGE-M/urine creatinine Part 2: - Urine LTE4/urine creatinine - Urine PGE-M/urine creatinine - Urine 2,3-dinor 6-keto PGF1a/urine creatinine - Urine 6-keto PGF1a/urine creatinine - Urine 11-dehydro TXB2/urine creatinine - Urine 11-dehydro TXB2/urine 2,3-dinor 6-keto PGF1a ratio In a subpopulation of patients in Part 2 the following PD endpoints will be determined: - PGE2 in synovial fluid - LTB4 in synovial fluid Efficacy endpoints: Part 1: - Patient global asse | — |
Countries
Czech Republic, Germany, Hungary, United Kingdom
Outcome results
None listed