Clinical trial NCT01265264: Study to Evaluate sUA Lowering Activity, Safety and Efficacy of Oral Ulodesine Added to Allopurinol
Official title: A Randomized, Double-Blind, Dose-Response Study of the Safety and Efficacy of Oral Ulodesine Added to Allopurinol in Subjects With Gout Who Have Not Adequately Responded to Allopurinol Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gout
Hyperuricemia
Arthritis
Joint Disease
Keywords: Gout
hyperuricemia
arthritis
joint diseases
allopurinol
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-12-23
Enrollment: 279
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether ulodesine and allopurinol combined for 12 weeks are effective in treating gout in patients who are not adequately responding to allopurinol alone.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 to \< 70 years
* Baseline sUA ≥ 6.0 mg/dL after at least 2 weeks of treatment on a stable 300 mg dose of allopurinol
* Documented diagnosis of gout according to the American Rheumatism Association --Preliminary Criteria for the Diagnosis of Gout
* Be willing and able to take colchicine 0.6 mg per day or naproxen 220-250 mg twice daily as prophylaxis for gout flares and, if needed, a single daily dose of a proton pump inhibitor to prevent gastrointestinal discomfort
* Female participants must:

  * Be sexually abstinent
  * Be surgically sterile
  * Be postmenopausal or on stable contraception
* Male participants must:

  * Be sexually abstinent
  * Be \> 1 year post-vasectomy
  * Using condoms with spermicide with partners meeting female requirements

Exclusion Criteria:

* Unable to tolerate 300 mg allopurinol
* Unable to tolerate both colchicine 0.6 mg per day and naproxen 220-250 mg twice daily
* Prior participation in a clinical study with BCX4208
* Gout flare during the Screening Period that is resolved for less than 2 weeks prior to first treatment with BCX4208 or placebo (exclusive of chronic synovitis/ arthritis)
* Unstable angina, symptomatic arrhythmia, signs or symptoms compatible with New York Heart Association Class III or Class IV heart failure, history of long QT syndrome, or QTc interval \< 350 msec or \> 475 msec
* Poorly controlled hypertension (SBP \> 160 mmHg or DBP \> 100 mmHG at Screening or Baseline)
* Moderate or severe renal impairment and/or calculated creatinine clearance of \< 60 mL/min(Cockroft-Gault method)
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values \> 2.0 x ULN
* CD4+ cell counts by flow cytometry \< 500 cells/mm3
* Hemoglobin \< 10 g/dL or \> 18 g/dL males or \< 10 g/dL or \> 17 g/dL females White blood cell count \< 3.7 x 109/L or \> 11 x 109/L
* Female subjects who are pregnant, breastfeeding, or planning a pregnancy within the next 4 months
* Positive serology for hepatitis B surface antigen or hepatitis C or HIV type 1
* Immunocompromised or on systemic immunosuppressive medications or antirheumatic drugs (including anakinra and adrenocorticotropic hormone)from Screening to Day 92
* Azathioprine or 6-mercaptopurine within 14 days of first dose of allopurinol Hydrochlorothiazide in doses \> 50 mg per day from Screening to Day 92
* Use of herbal/dietary supplements Screening to Day 92
* Recipient of any live or attenuated vaccine within 6 weeks of Screening
* Uric acid-lowering drugs other than allopurinol from Screening to Day 92 Systemic corticosteroids within 4 weeks prior to Day 1 (this does not include pulmonary or nasal inhaler containing corticosteroids, ophthalmic corticosteroids, joint injections, or low potency topical steroids)
* Investigational drug within 30 days prior to signing the ICF for this study
* Clinically significant and relevant drug allergies
* Chronic or recurrent infections (≥ 3 infections at the same site within 12 months)
* Cancer within 12 months-Except non-melanomatous localized skin cancer or completely excised and cured carcinoma-in-situ of uterine cervix or subjects who were previously treated for prostate or breast cancer if they currently are stable and have not been on chemo therapy within the last year prior to screening.
* Alcohol or drug abuse within 12 months of signing the ICF, or current substance dependence or abuse
* Other medical conditions which, in the opinion of the PI, would jeopardize the safety of the study subject or impact the validity of the study results.

Primary outcomes:
measure: To evaluate the dose response of ulodesine when combined with Allopurinol on sUA.
timeFrame: Day 85
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Malvern
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Burbank
country: United States
state: California
city: Irvine
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oceanside
country: United States
state: California
city: Palm Springs
country: United States
state: California
city: Paramount
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Jose
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: West Covina
country: United States
state: California
city: Deland
country: United States
state: Florida
city: Edgewater
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Oldsmar
country: United States
state: Florida
city: Sanford
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Meridian
country: United States
state: Idaho
city: Gurnee
country: United States
state: Illinois
city: Brownsburg
country: United States
state: Indiana
city: Newton
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: Baltimore
country: United States
state: Maryland
city: Springfield
country: United States
state: Massachusetts
city: Lansing
country: United States
state: Michigan
city: Olive Branch
country: United States
state: Mississippi
city: Omaha
country: United States
state: Nebraska
city: Albuquerque
country: United States
state: New Mexico
city: Charlotte
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Greer
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Bristol
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Tacoma
country: United States
state: Washington
Study officials:
affiliation: BioCryst Pharmaceuticals
name: Alan Hollister, MD, PhD
role: STUDY_DIRECTOR
References: