Study to Evaluate sUA Lowering Activity, Safety and Efficacy of Oral Ulodesine Added to Allopurinol

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01265264
First received: December 20, 2010
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Gout
Hyperuricemia
Arthritis
Joint Disease
Drug: ulodesine
Drug: Placebo
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 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

Resource links provided by NLM:


Further study details as provided by BioCryst Pharmaceuticals:

Primary Outcome Measures:
  • To evaluate the dose response of ulodesine when combined with Allopurinol on sUA. [ Time Frame: Day 85 ] [ Designated as safety issue: Yes ]
    Level of serum uric acid levels be measured at Day 85 to evaluate in subjects with Gout.


Enrollment: 279
Study Start Date: December 2010
Study Completion Date: February 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ulodesine Placebo + Allopurinol 300mg
Oral dose administered daily for 84 days.
Drug: ulodesine
Oral dose administered daily for 84 days.
Drug: Placebo
Oral dose administered daily for 84 days.
Experimental: ulodesine 5mg + Allopurinol 300mg
Oral dose administered daily for 84 days.
Drug: ulodesine
Oral dose administered daily for 84 days.
Drug: Placebo
Oral dose administered daily for 84 days.
Experimental: ulodesine 10mg + Allopurinol 300mg
Oral dose administered daily for 84 days.
Drug: ulodesine
Oral dose administered daily for 84 days.
Drug: Placebo
Oral dose administered daily for 84 days.
Experimental: ulodesine 20mg + Allopurinol 300mg
Oral dose administered daily for 84 days.
Drug: ulodesine
Oral dose administered daily for 84 days.
Drug: Placebo
Oral dose administered daily for 84 days.
Experimental: ulodesine 40mg + Allopurinol 300mg
Oral dose administered daily for 84 days.
Drug: ulodesine
Oral dose administered daily for 84 days.
Drug: Placebo
Oral dose administered daily for 84 days.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01265264

  Show 54 Study Locations
Sponsors and Collaborators
BioCryst Pharmaceuticals
Investigators
Study Director: Alan Hollister, MD, PhD BioCryst Pharmaceuticals
  More Information

No publications provided

Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01265264     History of Changes
Other Study ID Numbers: BCX4208-203
Study First Received: December 20, 2010
Last Updated: October 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by BioCryst Pharmaceuticals:
Gout
hyperuricemia
arthritis
joint diseases
allopurinol

Additional relevant MeSH terms:
Arthritis
Gout
Joint Diseases
Hyperuricemia
Musculoskeletal Diseases
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes
Allopurinol
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 11, 2014