Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— Taski-2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00665925
• Other study ID #: C-935788-010
• Status: Completed
• Phase: Phase 2
• First received: April 22, 2008
• Last updated: May 5, 2011
• Start date: May 2008
• Est. completion date: June 2009

Study information

• Verified date: May 2011
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: 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 AgencyColombia: Ministry of Health (INVIMA: Instituto Nacional de Vigilancia de Medicamentos y Alimentos)Colombia: Ethics Committee (Ethic Committee of each institution)Hungary: National Institute of PharmacyIsrael: Ethics CommissionIsrael: Israeli Health Ministry Pharmaceutical AdministrationMexico: Ethics Committee (each site submits to their local EC).Mexico: Federal Commission for Protection Against Health RisksMexico: Federal Commission for Sanitary Risks ProtectionMexico: 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 ProductsRomania: National Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Fostamatinib disodium (R935788)
100 mg tablet, orally, twice-a-day 150 mg tablet, orally, once-a-day

Locations

Country	Name	City	State
Bulgaria	MMA HAT Pleven	Pleven
Bulgaria	MHAT "Kaspela"	Plovdiv	PLO
Bulgaria	MHAT Ruse	Ruse
Bulgaria	DCC "Sv. Anna" Sofia	Sofia
Bulgaria	MHAT "Sv. Ivan Rilski"	Sofia
Bulgaria	MMA HAT Sofia	Sofia	Gsof
Bulgaria	MNTranspH "Tsar Boris Treti"	Sofia	Gsof
Bulgaria	Tokuda Hospital Sofia	Sofia
Bulgaria	MHAT " Sveta Marina"	Varna
Colombia	Centro de Reumatologia y Ortopedia	Barranquilla	Atlántico
Colombia	Reumatologos del Caribe	Barranquilla	Atlántico
Colombia	CIREEM	Bogota	Cundinamarca
Colombia	Fundación Instituto de Reumatología	Bogota	Cundinamarca
Colombia	Riesgo de Fractura S.A	Bogota	Cundinamarca
Colombia	Private Office	Bogotá	Cundinamarca
Colombia	Centro Medico Carlos Ardila Lulle	Bucaramanga	Santander
Colombia	SERVIMED	Bucaramanga	Santander
Colombia	Unidad Medica Torre Plaza	Medellín	Antioquia
Israel	The Chaim Sheba Medical Center	Ramat Gan
Mexico	Centenario Hospital Miguel Hidalgo	Aguascalientes
Mexico	Christus Muguerza del Parque	Chihuahua
Mexico	Hospital Inovamed , Torre Médica	Cuernavaca	Morelos
Mexico	Hospital Civil de Guadalajara "Fray Antonio A	Guadalajara	Jalisco
Mexico	Instituto Jalisciense de Investigación Clínica	Guadalajara	Jalisco
Mexico	Hospital Aranda de la Parra	Leon	Guanajuato
Mexico	Arké Estudios Clínicos S.A de C.V	Mexico	D.f.
Mexico	Centro Médico DALINDE	Mexico	Distrito Federal
Mexico	Clínica para el Diagnostico y Tratamiento de	Mexico	D.f.
Mexico	Hospital Ángeles Metropolitano	Mexico	D.f.
Mexico	Hospital General de México	Mexico	D.f.
Mexico	Star Médica	Morelia	Michoacán
Poland	NZOZ Centrum Medyczne Artur Racewicz	Bialystok
Poland	SPZOZ Szpital Wojewodzkiim J. Biziela	Bydgoszcz
Poland	Szpit. Spec.Nr 1, Odz. Reumatol. i Reh.	Bytom
Poland	Wojewodzki Szpital Zespolony Oddzial Reumatol	Elblag
Poland	Mazowieckie Centrum Badan Klinicznych	Grodzisk Mazowiecki
Poland	Krakowskie Centrum Medyczne NZOZ	Krakow
Poland	Malopolskie Centrum Medyczne SC	Krakow
Poland	NZOZ Reumed	Lublin
Poland	SCD-Med. Bamberski Dwor Sp. z o.o.	Poznan
Poland	NZOZ "Nasz Lekarz"	Torun
Poland	WIM Klinika Chorob Wewnetrznych i Reumatologi	Warsaw
Poland	Centrum Medyczne Osteomed	Warszawa
Poland	ASK Klinika Reumatologii i Chor. Wewn.	Wroclaw
Poland	Synexus SCM	Wroclaw
Poland	ZOZ w Zyradowie Oddzial Reumatologii	Zyradow
Romania	CMI "Cristei R. Dorica"	Braila
Romania	Spitalul Clinic "Sf. Maria" Med Int si Reumat	Bucuresti	Sector 1
Romania	Spitalul de Urgenta al MAI Dr. D. Gerota	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj Reum	Cluj-Napoca	Cluj
Romania	Spitalul Judetean "Dr. Fogolyan Kristol"	Sf. Gheorghe
Romania	Spitalul Clinic Judetean Sibiu	Sibiu
United States	Austin Rheumatology & Research	Austin	Texas
United States	Rheumatology Associates	Charleston	South Carolina
United States	Rheumatology Associates, SC	Chicago	Illinois
United States	Arthritis Associates of Colorado Springs	Colorado Springs	Colorado
United States	Center for Arthritis & Osteoporosis	Elizabethtown	Kentucky
United States	Rheumatology Associates	Erie	Pennsylvania
United States	Florida Medical Research Institute	Gainsville	Florida
United States	Holzer Clinic	Gallipolis	Ohio
United States	The Osteoporosis & Clinical Trials Center	Hagerstown	Maryland
United States	Arthritis & Osteoporosis Center, PC	Hamden	Connecticut
United States	Divison of Rheumatology Allergy and Immunology	La Jolla	California
United States	Fiechtner Research, Inc.	Lansing	Michigan
United States	Paddock Park Clinical Research	Ocala	Florida
United States	Health Research of Oklahoma	Oklahoma	Oklahoma
United States	Westroads Medical Group	Omaha	Nebraska
United States	Jeffrey Poiley, MD	Orlando	Florida
United States	Desert Medical Advances	Palm Desert	California
United States	North Carolina Arthritis & Allergy Care Center	Raleigh	North Carolina
United States	Rockford Health Physician	Rockford	Illinois
United States	University of California at Davis Medical Center	Sacramento	California
United States	Arthritis Center of South Texas	San Antonio	Texas
United States	Lovelace Scientific Resources	Sarasota	Florida
United States	Memorial Medical Group Clinical Research Inst	South Bend	Indiana
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Cynthia Morgan	Washington	District of Columbia
United States	Clinical Research Center of Reading, LLP	West Reading	Pennsylvania
United States	Rheumatic Disease Associates	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Bulgaria,  Colombia,  Israel,  Mexico,  Poland,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	confirm the efficacy of R788 100 mg PO bid as determined by ACR20 responder rates at 6 months.		6 months	No
Secondary	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		6 months	No
Secondary	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		Week 1 and Week 2	No
Secondary	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		6 month	No
Secondary	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		Study	Yes