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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Zalicus
ClinicalTrials.gov Identifier:
NCT01369745
First received: June 7, 2011
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Prednisolone
Drug: dipyridamole
Drug: Prednisone
Drug: Z102
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Double-Blind, Placebo-Controlled, Multi-Center, Randomized Withdrawal Design Trial Using Adaptive Randomization Comparing Z-102 With Placebo In Patients With Moderate To Severe Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Zalicus:

Primary Outcome Measures:
  • Change From Baseline in DAS28-CRP at 12 Weeks [ Time Frame: baseline to week 12 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Change From Baseline in DAS28-CRP Individual Components at 12 Weeks [ Time Frame: Baseline to week 12 ] [ Designated as safety issue: No ]

    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.


  • Percentage of Subjects Achieving ACR20, ACR50 and ACR70 at 12 Weeks [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.

  • Multidimensional Assessment of Fatigue (MAF) at Week 12 [ Time Frame: week 12 ] [ Designated as safety issue: No ]

    The Multidimensional Assessment of Fatigue (MAF) scale contains 16 items and measures four dimensions of fatigue: severity (#1-2), distress (#3), degree of interference in activities of daily living (#4-14), and timing (#15-16). Fourteen items contain numerical rating scales (#1-14) and two items have multiple-choice responses (#15-16). Respondents are asked to reflect on fatigue patterns for the past week.

    To calculate the Global Fatigue Index (GFI): Convert item #15 to a 0-10 scale by multiplying each score by 2.5 and then sum items #1, 2, 3, average #4-14, and newly scored item #15.

    Scores range from 1 (no fatigue) to 50 (severe fatigue). Do not assign a score to items #4-14 if respondent indicated they "do not do any activity for reasons other than fatigue." If respondents select no fatigue on item #1, assign a zero to items #2-16. Item #16 is not included in the Global Fatigue Index.


  • Time to Failure (Days) [ Time Frame: Baseline to 12 weeks ] [ Designated as safety issue: No ]
    Patients will be monitored for addition of any DMARD or withdrawal due to flare. The time to failure is defined as the duration of study participation (in days) until a qualifying event or completion of study treatment, whichever comes first.


Enrollment: 294
Study Start Date: June 2011
Study Completion Date: September 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Prednisolone
Prednisolone 2.7 mg daily for 12 weeks
Drug: Prednisolone
Prednisolone 2.7 mg daily
Active Comparator: dipyridamole
Dipyridamole 360 mg daily for 12 weeks
Drug: dipyridamole
dipyridamole 360 mg daily
Active Comparator: prednisone
Prednisone 5 mg daily for 12 weeks
Drug: Prednisone
Prednisone 5 mg daily
Experimental: Z102 (2.7/360)
Prednisolone 2.7 mg plus dipyridamole 360 mg daily for 12 weeks
Drug: Z102
Prednisolone 2.7 mg plus dipyridamole 360 mg daily
Other Names:
  • prednisolone
  • dipyridamole
Placebo Comparator: placebo
Placebo daily for 12 weeks
Other: placebo

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01369745

Locations
United States, Ohio
Zalicus Investigational Site
Toledo, Ohio, United States, 43606
Sponsors and Collaborators
Zalicus
Investigators
Study Director: Margaret Lee, PhD Zalicus, Inc.
  More Information

No publications provided

Responsible Party: Zalicus
ClinicalTrials.gov Identifier: NCT01369745     History of Changes
Other Study ID Numbers: Z102-008
Study First Received: June 7, 2011
Results First Received: February 10, 2014
Last Updated: April 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Zalicus:
Rheumatoid Arthritis
Moderate to severe

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisone
Prednisolone hemisuccinate
Prednisolone phosphate
Dipyridamole
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2014