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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 18 September 2012
Main ID:  EUCTR2010-023782-22-ES
Date of registration: 20/07/2011
Prospective Registration: Yes
Primary sponsor: Pfizer, S.L.U.
Public title: A TRIAL TO TEST THE EFFICACY AND SAFETY OF STUDY DRUG PF-04171327(1,5,10, 15 MG DOSE, DAILY) COMPARED TO 5 MG AND 10 MG PREDNISONE DAILY AND PLACEBO DAILY FOR SUBJECTS WITH RHEUMATOID ARHTRITIS OVER A PERIOD OF 8 WEEKS FOLLOWED BY 4 WEEKS OF TAPERING OF STUDY DRUG
Scientific title: A PHASE 2, RANDOMIZED, DOUBLE-BLIND ASSESSMENT OF EFFICACY AND SAFETY OF PF-04171327(1, 5, 10, 15 MG DOSE, DAILY) COMPARED TO 5 MG AND 10 MG PREDNISONE DAILY AND PLACEBO DAILY IN SUBJECTS WITH RHEUMATOID ARTHRITIS OVER AN 8 WEEK PERIOD FOLLOWED BY A 4 WEEK PERIOD OF TAPERING OF STUDY DRUG
Date of first enrolment: 16/12/2011
Target sample size: 315
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023782-22
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: Prednisone Number of treatment arms in the trial: 7  
Phase: 
Countries of recruitment
Bulgaria Canada Colombia Czech Republic Germany Hungary India Korea, Republic of
Malaysia Mexico Poland Romania Russian Federation Serbia Slovakia South Africa
Spain Ukraine United States
Contacts
Name: Clinical Trials.gov Call Center   
Address:  235 East 42nd Street NY 10017 New York United States
Telephone: 0018007181021N/A
Email: ClinicalTrials.govCallCenter@pfizer.com
Affiliation:  Pfizer Inc.
Name: Clinical Trials.gov Call Center   
Address:  235 East 42nd Street NY 10017 New York United States
Telephone: 0018007181021N/A
Email: ClinicalTrials.govCallCenter@pfizer.com
Affiliation:  Pfizer Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects
of the study. 2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 3. Males and females >18 years of age. 4. Subject should have RA (ACR criteria, 1987 revised criteria) with a minimum duration of
3 months and fulfilled 4/7 criteria for the diagnosis of RA. 5. Subject must have minimum disease activity level of at least:
?6 swollen joints and ?6 tender joints at screening and baseline (28 joint count); CRP ?0.7 mg/dL (?7.0 mg/L) at screening.
6. Meet the ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II or III. 7. Subject must have been on MTX or allowed MTX-DMARD combination (eg, MTX + hydroxychloroquine or MTX + chloroquine or MTX + sulfasalazine) for at least 3 months, and be on a stable dose of MTX for at least 8 weeks prior to screening. MTX or
allowed DMARD combination, as well as any concomitant medication(s) dose, will remain unchanged during the treatment period. 8. Subject must be on a stable MTX of dose ?7.5 mg weekly (po/sc/im) and ?25 mg weekly unless documented intolerance requires a lower dose. Stable MTX doses should be administered as a weekly single dose for a minimum of 8 weeks prior to randomization. 9. For subjects on chronic topical or inhaled glucocorticoids, the treatment must be stable for ?4 weeks prior to entry and remain unchanged throughout the study period. 10. No evidence of active or latent infection with Mycobacterium tuberculosis (TB) as defined by all of the following: A negative QuantiFERON; TB Gold In Tube test or, if unavailable, a Mantoux Purified Protein Derivative (PPD) skin test using 5 tuberculin units per 0.1 mL (5 TU PPD) result of <5 mm of induration, performed within the 3 months prior to screening. [It is strongly recommended that patients with a history of Bacille Calmette Guérin (BCG) vaccination be tested with the QuantiFERON; No history of previously untreated infection with TB, and not currently receiving treatment for active TB; A chest radiograph taken within the 3 months prior to screening without changes suggestive of active TB infection. If a patient has a positive QFT Gold or PPD test, he/she may be eligible if he/she has completed an appropriate treatment regimen for TB and has a chest radiograph within the 3 months prior to Screening that shows no evidence of active TB. A subject who is currently being treated for latent TB infection can only be enrolled with documentation of an adequate treatment regimen, a chest radiograph within the 3 months prior to Screening that shows no evidence of active TB, and with approval by the Sponsor. In addition, patients must have maintained normal ALT and AST levels following initiation of treatment for latent TB (minimum of 1 month) duration of latent TB treatment prior to PF-04171327 dosing.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65

Exclusion criteria:
1. Diagnosis of any other arthritidies (inflammatory or non-inflammatory) or chronic pain condition (fibromyalgia, neuropathy) that, in the opinion of the investigator would interfere with disease activity assessments. 2. Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological disease, or any other conditions which would make the subject unsuitable for the study. 3. Any lymphoproliferative disorder, such as Epstein-Barr Virus (EBV), history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma or signs andsymptoms suggestive of current lymphatic disease. 4. A prior history of malignancy, excluding subjects with non-metastic basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, who are eligible immediately after adequate treatment. 5. Blood dyscrasis including confirmed:Hemoglobin <9 g/dL or Hematocrit <30%; Absolute white blood cell (WBC) count <3.0 x 10 to the power of 9/L; Absolute neutrophils count <1.2 x 10 to the power of 9/L; Platelet count<100 x 10 to the power of 9/L. 6. Subjects treated with the following who did not observe the protocol specified wash out period before baseline: CYP3A4 inducers or inhibitors, Experimental NSAIDs,herbal medications, Immunization with any live or live attenuated virus vaccination (egg, FluMist?), Glucocorticoids by any route that may result in significant systemic exposure, Biologic DMARDs, Anakinra (Kineret®), etanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Golimumab (Simponi TM), Abatacept (Orencia®), tocilizumab (Actemra), certolizumab pegol (Cimzia®), rituximab(Rituxan®) or other selective B lymphocyte depleting agents, DMARDs, d-penicillamine, azathioprine, cyclosporine, tacrolimus, and staphylococcal protein. Immuno-absorbant pheresis columns (eg, PROSORBA device/column), Tetracyclines, unless prescribed for the treatment of acne or other dermatologic disorders, Auranofin (oral gold), aurothioglucose (injectable gold), aurothiomalate (injectable gold), Leflunomide (Arava®). 7. All investigational compounds must be discontinued for four weeks or 5 half-lives (whichever is longer) prior to Day 0 Prior exposure to investigational biologics should be discussed with the Pfizer Medical Monitor, as these agents may require expanded washout periods. 8. Hepatic enzyme elevations (ALT or ALP) >1.2 ULN. 9. Subject diagnosed with insulin dependent diabetes mellitus or poorly controlled noninsulin dependent diabetes mellitus (HgbA1c value of >8.0%). 10. Drug or alcohol abuse with less than 6 months of continued abstinence prior to the screening visit. 11. Clinically significant infections (those requiring hospitalization or requiring parenteral antimicrobial therapy) within 6 months of the screening visit. 12. A body temperature of 38?C or higher at the baseline visit or a febrile illness within 14 days prior to the first dose. 13. An infection with human immunodeficiency virus (HIV) or Hepatitis B or C. 14. Any condition possibly affecting oral drug absorption 15. Significant trauma, blood loss or major surgery (involving anesthesia or respiratory assistance within 4 weeks of the screening visit). 16. Bone fracture and/or immobility/immobilization within 3 months of the screening visit. 17. A standard 12-lead ECG demonstrating a QTcF >450 ms for males and QTcF >480 ms for females or other clinically significant abnormality at the screening visit If t


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
MedDRA version: 14.0 Level: LLT Classification code 10066578 Term: Progression of rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Intervention(s)

Product Code: PF-04171327
Pharmaceutical Form: Tablet
CAS Number: 1044535-58-1
Current Sponsor code: PF-04171327
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Code: PF-04171327
Pharmaceutical Form: Tablet
CAS Number: 1044535-58-1
Current Sponsor code: PF-04171327
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Code: PF-04171327
Pharmaceutical Form: Tablet
CAS Number: 1044535-58-1
Current Sponsor code: PF-04171327
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Decortin
Pharmaceutical Form: Capsule
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-02
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: -To compare efficacy and safety of PF-04171327 (1, 5, 10 mg, 15 mg once daily) to 5 mg daily prednisone, 10 mg daily prednisone and placebo given over 8 weeks, in subjects with active RA on a stable background of MTX;

- Determine comparative therapeutic window of PF-04171327 using ACR 20 responses and change from baseline in P1NP and UNTx/Ucr, (primary set of biomarkers) ie, determining a dose, or a range of doses, in which there is sufficient efficacy on the ACR20 and minor changes in P1NP and UNTx/Ucr.
Primary end point(s): - Efficacy: ACR20 at week 8; Primary set of dissociation biomarkers: P1NP, and UNTx/Ucr at week 8.
Secondary Objective: To characterize the dose-effect and concentration-effects for efficacy, safety and biomarker outcome measures;
- To characterize the effects of PF-04171327 on the bone and carbohydrate biomarkers compared to prednisone 5 mg, 10 mg, and placebo;
-To examine the durability of the response to PF-04171327;
-To evaluate the tapering of PF-04171327;
-To evaluate the safety and tolerability of PF-04171327;
- To evaluate health and functional status of study subjects.
Timepoint(s) of evaluation of this end point: Study Week 8
Secondary Outcome(s)
Secondary end point(s): Efficacy:
- ACR20 at 2, 4 and 12 weeks; ACR50, ACR70, Hybrid ACR response, Individual ACR components, all at week 2, 4, 6, 8 and 12;
- DAS 28-3 (CRP), DAS28-4 (CRP) at week 2, 4, 6, 8 and 12;
- SF-36 v 2 (Quality of Life) at week 4, 8, and 12.

Pharmacokinetic and Pharmacodynamic endpoints:
- Plasma concentrations of PF-00251802 and its N-Oxide metabolite PF-04015475 (baseline, week 2, 4, 6 and 8
- Pharmacodynamic effects will be assessed by several biomarkers, such as serum CTX, osteocalcin, PTH and adiponectin at baseline, week 2, 4, 6, 8, 10, 12 and 13.

Safety endpoints:
-Biomarkers: plasma cortisol, CRP, will be obtained at baseline, week 2, 4, 6, 8, 10, 12 and 13
- Circulating lymphocytes, neutrophils, and eosinophil counts will be obtained at 4,8 and 12 weeks
- HbA1C(baseline week 8 and 12), and fasting glucose at week 0,4,8 and 12.

Safety outcomes: Assessment of taper period, HPA axis labs (ACTH stimulation test (week 13 after one week of study drug discontinuation), vital signs, telephone follow up (taper period), AE reports, routine labs (including liver tests), concomitant meds (esp. diabetes meds, glucocorticoids other than study drug).
Timepoint(s) of evaluation of this end point: Study Weeks 2, 4, 6, 8 and 12
Secondary ID(s)
A9391010
Source(s) of Monetary Support
Pfizer Inc.
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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