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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 March 2013
Main ID:  EUCTR2011-000436-28-PL
Date of registration: 20/06/2011
Prospective Registration: Yes
Primary sponsor: Zalicus, Inc.
Public title: A trial to compare Z102 against placebo in patients with Rheumatoid Arthritis.
Scientific title: A PHASE II, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTI-CENTER, RANDOMIZED WITHDRAWAL DESIGN TRIAL USING ADAPTIVE RANDOMIZATION COMPARING Z102 WITH PLACEBO IN PATIENTS WITH MODERATE TO SEVERE RHEUMATOID ARTHRITIS
Date of first enrolment: 07/12/2011
Target sample size: 250
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000436-28
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 5  
Phase: 
Countries of recruitment
Argentina Brazil Bulgaria Chile Hungary Mexico Peru Poland
Russian Federation Serbia Ukraine United States
Contacts
Name: Clinical Trial Information    
Address:  1000 Continental Drive PA 19406 King of Prussia United States
Telephone: +0016109642012
Email: meera.jessani@wwctrials.com
Affiliation:  Worldwide Clinical Trials
Name: Clinical Trial Information    
Address:  1000 Continental Drive PA 19406 King of Prussia United States
Telephone: +0016109642012
Email: meera.jessani@wwctrials.com
Affiliation:  Worldwide Clinical Trials
Key inclusion & exclusion criteria
Inclusion criteria:
Each patient must meet all of the following inclusion criteria to be
enrolled in the study:

1.Prior to screening have voluntarily signed the informed consent form.

2.At Screening be at least 18 years of age.

3.At screening meet the ACR / EULAR criteria for classification of
RA which include:
o Joint involvement
o Serology
o Acute-phase reactants
o Duration of symptoms

4. At screening have moderate to severe RA, defined as involving a
minimum (=6 total swollen and =6 total tender) of the 28 joints
assessed.

5. At screening have screening CRP levels of at least 0.6 mg/dl and a DAS28-CRP score =4.5.Retesting of the CRP and recalculation of DAS28-CRP (due to CRP <0.6 mg/dL) is allowed one time.

6. Have been on DMARD therapy for at least 90 days, have been on stable DMARD dose without dosage adjustment or modification for 6 weeks, and should be able to maintain the same dose of conventional DMARD therapy during study participation (with or without glucocorticoid therapy). Stable DMARD therapy may include a combination of DMARD agents (methotrexate and azsulfadine or methotrexate and hydroxychloroquine as examples).

7. At screening female patients of childbearing potential (18 to 55 years of age, inclusive) must have negative urinary BhCG tests at enrollment and study completion.

8. Female patients of childbearing potential (18 to 55 years of age,
inclusive) must use acceptable methods of birth control (including, but not limited to, IUD, oral or injectable contraceptives, or barrier methods) while in the study.

9. If currently taking the following medications she/he has been on a stable dose of the same drug for at least 3 months prior to entering into the trial and will continue on the same dose for the duration of the trial:
statins, diuretics, thyroid hormone, hypoglycemic medications, and
cardiovascular medications.
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 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion criteria:
1.Female patient is pregnant,actating,or of child bearing potential not using acceptable methods of birth control including,but not limited to,IUD,oral or injectable contraceptives,barrier methods or abstinence
2.Patients who do not respond to therapies that include a dose < 10mg prednisone and either a DMARD combination,DMARDbiologic
combination or biologics alone
3.Active cardiovascular disease,unless well controlled by appropriate treatment for a minimum of 3months prior to screening
4. taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325mg
5.Taking oral steroids at a daily prednisone dose,or the equivalent,of >10mg/day within the past 2weeks
6.Intraarticular,intramuscular,or intravenous glucocorticoids must not have been given at least 6weeks prior to entering the study or be anticipated to be given at any time during the study
7.The need to continue the use of one or multiple NSAIDs at the same time,or the use of acetaminophen on a chronic basis.
Ataminophen/paracetamol will be permitted episodically for pain during the trial,not exceeding 1.5gper day for any 3days in any 7day interval.There are no exclusions during the 30day followup period
8.All opiate use is prohibited.Such agents include oxycodone,
hydrocodone,codeine,morphine sulfate,Demero (meperidine/pethidine),Dilaudid(hydromorphone),combi nation products including Percocet(oxycodone and acetaminophen),Hydrocet(dihydrocodeine
andacetaminophen),Tylenol(acetaminophen or paracetamol) with
codeine,Vicodin(hydrocodone and acetaminophen),Lorcet(hydrocodone and acetaminophen),Lortabs(hydrocodone and acetaminophen)and extended-release formulations
9.Use of any other medications or herbs or non pharmacological
treatments eg acupuncutre used for the treatment of pain is prohibited
10.Excluded medications include Drugs known to interact with
dipyridamole(egadenosine, cholinsteraseb inhibitors,theophylline,caffeine and other xanthine derivatives)or with prednisolone(eganticoagulants,antifungals and HIV protease
inhibitors)Systemic anticoagulants,including dipyridamole,Coumadin(warfarin),clopidogrel,ticlopidine and aspirin exceeding 325mg/day(whether or not taken for cardiovascular prophylaxis) All Systemic antifungal agents, including but not limited to the polyene macrolides(amphotericin B),the azole (ketoconazole,miconazole,itraconazole and fluconazole) and the
allylamines(terbinafine) All antiHIV drugs belonging to the following
classes:members of the nucleoside/nucleotide reverse transcriptase inhibitors,nonnucleoside/ nucleotide reverse transcriptase inhibitors,protease inhibitors,fusion and entry inhibitors and integrin inhibitors.These agents include but are not limited to abacavir,zidovudine,didanosine,tenofovir and efavirenz.
11.Has,or has had,any active severe infections,such as
osteomyelitis,sepsis,active infectious hepatitis,endocarditis, systemic fungal infection or recent invasive surgical procedures within 30days of study initiation
12.Tuberculosis At screening patients with a history of or currently
active tuberculosis as per specific country guidelines are excluded
Patients with a positive Chest XRay eg apical thickening compatible with TB exposure/latency are excluded Patients who have a positive PPD test, in association with compatible signs and symptoms and/or a positive or indeterminate QFT are
excluded Note:A patient with a previous positive PPD test is at risk for development


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Treatment of patients with moderate to severe rheumatoid arthritis (RA)
MedDRA version: 14.1 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 10021428 - Immune system disorders
Intervention(s)

Product Name: Z102
Product Code: Z102
Pharmaceutical Form: Capsule
INN or Proposed INN: Z102 (Prednisolone and Dipyridamole).
Current Sponsor code: Z102 (Prednisolone and Dipyridamole).
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 360-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Prednisolone
Product Code: Prednisolone
Pharmaceutical Form: Capsule
INN or Proposed INN: Prednisolone
CAS Number: 52438-85-4
Current Sponsor code: Prednisolone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.7-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Dipyridamole
Product Code: Dipyridamole
Pharmaceutical Form: Capsule
INN or Proposed INN: Dipyridamole
CAS Number: 58-32-2
Current Sponsor code: Dipyridamole
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 180-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Dacortin ®
Pharmaceutical Form: Capsule
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: The primary objective of the study is to demonstrate the efficacy of Z102 2.7/360 versus placebo on the Disease Activity Score 28 C-reactive protein (DAS28-CRP) in patients with RA at the study endpoint of 12 weeks.
Primary end point(s): The primary endpoint is the change in the DAS28-CRP score at the 12-week visit from the baseline DAS28-CRP pain score. The DAS28-CRP score measured at 4 and 8 weeks will be used by the adaptive modeling in order to learn efficiently about the 12-week effects of each of the treatment arms. A difference between arms of a 0.25 effect (mean change divided by the standard deviation) is considered meaningful for futility analyses. A difference less than this is considered unimportant.

We label the change from baseline in the DAS28-CRP score for subject i at weeks 4, 8, and 12 weeks as Yi4, Yi8, and Yi12, respectively.
Secondary Objective: • Demonstrate the clinical efficacy of Z102 2.7/360 versus the separate components of Z102 (2.7 mg prednisolone and360 mg dipyridamole) and versus 5 mg prednisone, as measured by the DAS28-CRP score, in patients with RA at the study endpoint of 12 weeks

• Examine the efficacy ofZ102versus its separate components on the secondary outcome measures and assessment tools.
oDAS28-CRP
oDAS28-CRP individual components
Tender Joint Count
Swollen Joint Count
Patient Global Assessment of Disease Activity
CRP
oAmerican College of Rheumatology ACR20, ACR50, ACR70, which
includes
Tender Joint Count
Swollen Joint Count
Patient Global Assessment of Disease Activity
Physician Global Assessment of Disease Activity
Health Assessment Questionnaire
Patient Pain Visual Analog Scale
oMultidimensional Assessment of Fatigue
oTime to failure addition of a disease modifying anti-rheumatic drug or withdrawal due to flare
Timepoint(s) of evaluation of this end point: Baseline to week 12.
Secondary Outcome(s)
Secondary end point(s): N/A
Timepoint(s) of evaluation of this end point: N/A
Secondary ID(s)
Z102-008
Source(s) of Monetary Support
Zalicus, Inc.
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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