A 12-WEEK, PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED STUDY TO INVESTIGATE THE SAFETY, PHARMACOKINETICS, AND EFFICACY OF PH-797804, ADMINISTERED ORALLY ONCE DAILY IN SUBJECTS WITH ACTIVE RHEUMATOIDARTHRITIS. - na
- Conditions
- Treatment of rheumatoid arthritis (RA)MedDRA version: 8.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2006-003577-27-EE
- Lead Sponsor
- Pfizer Luxembourg SARL Branch Office Estonia
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 290
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
1. Has provided written informed consent and is willing to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures;
2. Is >18 years of age;
3. Has had at least 1 DMARD regimen failure;
4. In the last 6 months prior to the Screen visit, has been diagnosed with RA based upon the American College of Rheumatology (ACR) 1987 Revised Criteria, ie, fulfilling at least 4 of the following 7 criteria:
• Morning stiffness in and around any joint for more than 1 hour;
• Soft tissue swelling of 3 or more joint areas;
• Swelling of the proximal interphalangeal (PIP), metacarpophalangeal (MCP), or wrist joints;
• Symmetrical joint swelling;
• Rheumatoid nodules;
• Serum rheumatoid factor positive;
• Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.
5. In their current treatment regimen, maintains a minimum current level of disease activity characterized by:
• =6 joints tender or painful on motion (28-joint count),
• =6 joints swollen (28-joint count), AND
• C-reactive protein (CRP) =1 mg/dL (10 mg/L);
6. Meets the ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II,
or III (see Appendix 1of the protocol);
7. Has observed the washout periods if treated with any of the following therapies:
• Within 4 weeks of first dose:
Biologics —anakinra (Kineret®), etanercept (Enbrel®);
DMARDs —leflunomide (Arava® —see additional washout information for leflunomide in 5.7), auranofin (oral gold), injectable gold (aurothioglucose or
aurothiomalate), methotrexate, sulfasalazine, and d-penicillamine;
Immunosuppressive/Immunomodulatory therapies —azathioprine, cyclosporine,
minocycline, and PROSORBA® device/column;
NSAIDs —any experimental nonselective or selective NSAID (COX-2 inhibitor)
within a clinical trial setting with the exception of celecoxib [Celebrex®] for which a
washout interval of 72 hours shall apply);
Other —herbal medications, immunization with any live virus vaccination (eg, FluMist®), intra-articular, intramuscular, or intravenous corticosteroids;
• Within 8 weeks of first dose: infliximab (Remicade®), adalimumab (Humira®);
• Within 6 months of first dose: abatacept (Orencia®);
• Within 12 months of first dose: rituximab (Rituxan®), alemtuzab (CamPath®).
8. If female, has met either of criterion a.” or b.” below:
a. If of nonchildbearing potential, has met 1 of the following criteria:
• Amenorrheic for at least 2 years, or
• Has had a hysterectomy and/or bilateral oophorectomy at least 8 weeks prior to
screening;
Hence, all other female subjects (including those with tubal ligations) will be considered of childbearing potential.
b. If of childbearing potential, must be willing to use the acceptable methods of
contraception and abide by the timelines of each method as outlined in
Section 4.4.1.1 (protocol);
9. If male, must be willing to use the acceptable methods of contraception and abide by the timelines as outlined in Section 4.4.1.2 (protocol);
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
1. A diagnosis of any other inflammatory arthritis (eg, spondyloarthropathies) or
fibromyalgia (active RA with secondary osteoarthritis is acceptable);
2. A history of:
• Severe, progressive, and/or uncontrolled renal, hepatic, hematological,
gastrointestinal, endocrine, pulmonary, cardiac, neurological disease within 6 months
of first dose;
• Significant associated cardiac disease (eg, prior Coronary Artery Bypass Graft
[CABG], myocardial infarction, ischemic myocardial disease, congestive heart
failure, known arrhythmias of ventricular etiology, cardiomyopathy, unexplained
syncope or syncope/seizures related to arrhythmia);
• Chronic or recent serious or life-threatening infection within 6 months of first dose;
• Tuberculosis without treatment and/or positive tuberculin reaction to PPD (Purified
Protein Deriviative) without known vaccination with the bacilli Calmette-Guerin
vaccine (BCG). Refer to Section 7.2.3.1 of the protocol for additional clarification;
• A positive T-SPOT .TB, where used;
• Significant trauma or major surgery within 8 weeks of first dose of study medication;
• Alcohol abuse with less than 6 months of sobriety; drug abuse within 3 years of study start;
• Cancer, which has been in remission for <5 years excluding subjects with adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
3. Presenting with:
• Any condition possibly affecting oral drug absorption (eg, gastrectomy or clinically
significant diabetic gastroenteropathy);
• Any clinically significant skin lesions as described in CTCAE Version 3.0
(Appendix 2 of protocol);
• A body temperature >38°C (98.6°F) at Baseline;
• An infection with human immunodeficiency virus (HIV) or Hepatitis B or C;
• Any clinically significant active infection including herpes lesions;
• New York Heart Association (NYHA) Class III-IV congestive heart failure requiring
treatment (Appendix 3 of protocol);
• A confirmed mean of the Screen triplicate QTc interval >450 ms;
• A clinically significant abnormal ECG finding.
4. Evidence of organ dysfunction or hematopoietic disorder based on any of the following assessments:
• Hgb <10 gm/dL, Hct <32%;
• Absolute WBC count <3.0 × 109/L (<3000/mm3);
• Neutrophil count =1.2 × 109/L (<1200/mm3);
• Platelet count <100 × 109/L (<100,000/mm3);
• AST (aspartate aminotransaminase), ALT (alanine aminotransaminase) >1.2 ULN;
• Total bilirubin >1.2 × ULN;
• Alkaline phosphatase >1.2 × ULN;
• Albumin <3.5 g/dL or 35 g/L due to known liver disease;
• Serum creatinine >ULN.
5. Subjects requiring prohibited concomitant medications (Appendix 4of the protocol);
6. Pregnant or breastfeeding subjects.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method