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
Conditions
Interventions
Product Name: Z102
Product Code: Z102
Pharmaceutical Form: Capsule
INN or Proposed INN: Z102 (Prednisolone and Dipyridamole).
Current Sponsor code: Z102 (Prednisolone and Dipyridamole).
Concentratio
Sponsors
Zalicus, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
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/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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.;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;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.;Timepoint(s) of evaluation of this end point: Baseline to week 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
Argentina, Brazil, Bulgaria, Chile, Hungary, Mexico, Peru, Poland, Russian Federation, Serbia, Ukraine, United States
Contacts
Public ContactClinical Trial Information
Worldwide Clinical Trials
Outcome results
None listed