A Phase II Trial Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis

Zalicus294 enrolled

Overview

Thus study will test an experimental drug called Z-102 (combination of prednisolone and dipyridamole) to treat patients with moderate to severe rheumatoid arthritis.

The primary objective of the study was to demonstrate the efficacy of Z102 (2.7 mg prednisolone/360 mg dipyridamole) versus placebo on the Disease Activity Score 28 using C reactive protein (DAS28-CRP) in subjects with rheumatoid arthritis at the study endpoint of 12 weeks

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

294

Conditions

Rheumatoid Arthritis

Interventions

PrednisoloneDRUG

Prednisolone 2.7 mg daily

dipyridamoleDRUG

dipyridamole 360 mg daily

PrednisoneDRUG

Prednisone 5 mg daily

Z102

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Meet the ACR / EULAR criteria for classification of RA * Have moderate to severe RA, defined as involving a minimum (≥6 total swollen and ≥6 total tender) of the 28 joints assessed * Have screening CRP levels of at least 0.6 mg/dl and a DAS28-CRP score ≥4.5 * Have been on a stable dose of conventional DMARD therapy for at least 90 days without dosage adjustment or modification and should be able to maintain the same dose of conventional DMARD therapy during study participation (with or without glucocorticoid therapy Exclusion Criteria: * Treatment-refractory patients are excluded * Has active cardiovascular disease, unless well controlled by appropriate treatment for a minimum of 3 months prior to screening * Is taking aspirin for reasons other than for cardiovascular prophylaxis or their total daily dose is greater than 325 mg * Is currently taking steroids at a daily prednisone dose, or the equivalent, of \>10 mg * Intraarticular, intramuscular, or intravenous glucocorticoids must not have been given at least 6 weeks prior to entering the study * The need to continue the use of one or multiple NSAID's at the same time, or the use of acetaminophen on a chronic basis * All opiate use is prohibited * Use of any other medications or herbs used for the treatment of pain is prohibited * Patients with a history of or currently active tuberculosis as per specific country guidelines are excluded * Has uncontrolled diabetes mellitus as defined by a serum glucose \>126 mg/dl * Knowingly has HIV infection or hepatitis * Has undergone administration of any investigational drug within 30 days of study initiation * All biologic agents are excluded for 90 days prior to Screening and throughout the study. * Has undergone administration of rituximab or any B-cell depleting investigational drugs within 6 months of study initiation * Has had a history of alcohol or drug abuse within the past 2 years * Has a history of hypersensitivity to glucocorticoids and/or dipyridamole

Locations (1)

Zalicus Investigational Site

Toledo, Ohio, United States

Outcomes

Primary Outcomes

Change From Baseline in DAS28-CRP at 12 Weeks

The primary efficacy endpoint was the mean change in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12. The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of \<3.2 suggests a low level of disease activity, while a score of \>5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤3.2 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores.

Time frame: baseline to week 12

Secondary Outcomes

Change From Baseline in DAS28-CRP Individual Components at 12 Weeks

The mean change in the individual components of the Disease Activity Score 28 using C-reactive protein (DAS28-CRP) from baseline to Week 12 which included individual assessment of Tender Joint Count (28-joint assessment), Swollen Joint Count (28-joint assessment), Patient Global Assessment of Disease Activity and absolute CRP level. In each case, higher scores indicate more disease activity. The DAS28-CRP is a composite measure of inflammation in Rheumatoid Arthritis and incorporates a tender and swollen joint count, CRP and Patient Global Assessment of Disease Activity expressed in a Gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of \<3.2 suggests a low level of disease activity, while a score of \>5.1 suggests a high level of disease activity.

Time frame: Baseline to week 12

Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks

The American College of Rheumatology (ACR) 20 is a widely accepted composite index of improvement in RA proposed by the ACR (Fransen and van Riel 2009). ACR20 refers to a composite improvement of 20% in swollen joint count, tender joint count, and 3 or more of the following 5 measures:Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient Pain VAS, Patient's self-addressed disability (HAQ) (Arnet 1988 and Felson 1995), Acute-phase reactant (ESR or CRP) The ACR 50 and ACR 70 are similar tools, used to indicate 50% and 70% improvement, respectively.

Data from ClinicalTrials.gov

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