Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (Taski-2)

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00665925
First received: April 22, 2008
Last updated: May 5, 2011
Last verified: May 2011
  Purpose

The purpose of this study is to determine whether the Spleen Tyrosine Kinase (Syk) inhibitor, R935788 (R788), at a dose of 100 mg, orally, twice-a-day, and/or a dose of of 150 mg, orally, once-a-day is effective in the treatment of Rheumatoid Arthrits in patients who have had an inadequate clinical response to methotrexate.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Fostamatinib disodium (R935788)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of Two Doses of R935788 in Rheumatoid Arthritis Patients Failing to Respond to Methotrexate

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • confirm the efficacy of R788 100 mg PO bid as determined by ACR20 responder rates at 6 months. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • compare response rates for R788 100 mg PO bid and R788 150 mg PO qd as determined by ACR20, ACR50, ACR70, ACRn, DAS28-CRP and DAS28-ESR response rates over 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the rapidity of onset of clinical effect among the R788 100 mg PO bid, R788 150 mg PO qd, and placebo groups as determined by ACR20 response rates at Weeks 1 and 2 [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • To compare changes for R788 100 mg PO bid and R788 150 mg PO qd in the FACIT-fatigue and SF-36 from baseline to 6 months [ Time Frame: 6 month ] [ Designated as safety issue: No ]
  • To assess and compare the safety profiles for R788 100 mg bid and R788 150 mg qd compared with placebo for effects on liver function tests, clinically significant reductions in peripheral neutrophil counts, G-I side effects and other adverse effect [ Time Frame: Study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 420
Study Start Date: May 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
R788, 100 mg tablet, orally, twice-a-day
Drug: Fostamatinib disodium (R935788)
100 mg tablet, orally, twice-a-day 150 mg tablet, orally, once-a-day
Other Name: R935788
Experimental: 2
R788, 150 mg tablet, orally, once a day
Drug: Fostamatinib disodium (R935788)
100 mg tablet, orally, twice-a-day 150 mg tablet, orally, once-a-day
Other Name: R935788
Placebo Comparator: 3
Placebo, orally, either once a day, or twice a day
Drug: Fostamatinib disodium (R935788)
100 mg tablet, orally, twice-a-day 150 mg tablet, orally, once-a-day
Other Name: R935788

  Eligibility

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

Inclusion Criteria:

  • Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
  • Males and females, 18 years of age or older, with active RA for at least 6 months prior to Day 1 dosing.
  • Patients must have been receiving weekly methotrexate doses (7.5-25 mg/week) for a minimum of 3 months prior to Day 1 dosing and must be receiving a stable MTX dose, with no change in route, for the previous 6 weeks prior to Day 1 dosing.

    `Patients must be receiving a folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing.

  • Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
  • The patient must otherwise be in good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period. See exclusion criteria for specific exclusions.
  • In the Investigator's opinion, the patient has the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol.

Exclusion Criteria:

  • The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator's opinion, could affect the conduct of the study. Specifically, excluded are patients with the following:

    1. uncontrolled or poorly controlled hypertension;
    2. other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder) or arthritis syndromes (gout, Lyme disease, Reiter's syndrome);
    3. recent (within past 2 months prior to Day 1 dosing) serious surgery or infectious disease;
    4. recent history (past 5 years prior to Day 1 dosing) of, or treatment for, a malignancy other than nonmelanomatous skin cancer, or any history of lymphoma;
    5. Hepatitis B ;
    6. Hepatitis C ;
    7. interstitial pneumonitis or active pulmonary infection on chest x-ray;
    8. Tuberculosis (TB): the TB skin test should be negative.
    9. known laboratory abnormalities.
  • The patient has a history of substance abuse, drug addiction or alcoholism. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled spirits= 1.5 oz or 44 mL.
  • The patient has been treated previously treated with R788 under a different protocol.
  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: NCT00665925

  Show 79 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Daniel B Magilavy, MD Rigel Pharmaceuticals
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MSD, AstraZeneca
ClinicalTrials.gov Identifier: NCT00665925     History of Changes
Other Study ID Numbers: C-935788-010
Study First Received: April 22, 2008
Last Updated: May 5, 2011
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health [Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica (ANMAT)]
Argentina: Independient Ethics Committee for Clinical Pharmacology Assays (Comite Independiente de Etica para Ensayos en Farmacologia clinica)
Argentina: Ethics Committee (Ethic Committee of each institution)
Brazil: Ethics Committee (Ethic Committee of each institution)
Brazil: Ministry of Health (Conselho Nacional de Saude, CNS)
Brazil: National Committee of Ethics in Research (Comissao Nacional de Etica em Pesquisa, CONEP)
Brazil: National Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria, ANVISA)
Bulgaria: Bulgarian Drug Agency
Colombia: Ministry of Health (INVIMA: Instituto Nacional de Vigilancia de Medicamentos y Alimentos)
Colombia: Ethics Committee (Ethic Committee of each institution)
Hungary: National Institute of Pharmacy
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Mexico: Ethics Committee (each site submits to their local EC).
Mexico: Federal Commission for Protection Against Health Risks
Mexico: Federal Commission for Sanitary Risks Protection
Mexico: Ministry of Health (Secretaria de Salud, SSA)
Peru: Ethics Committee (19 registered IECs, the one used for this study is Comite de Etica de la Universidad de San Martin de Porres, CEUSMP).
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs (Dirección general de medicamentos, insumos y drogas, DIGEMID)
Peru: Ministry of Health (Instituto Nacional de Salud, INS)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on October 23, 2014