Study to Evaluate sUA-Lowering Activity, Safety & PK Interaction of Oral BCX4208 & Allopurinol Admin. in Subjects w/Gout

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01129648
First received: May 21, 2010
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

To evaluate safety and efficacy of BCX4208 alone and in combination with allopurinol in subjects with gout.


Condition Intervention Phase
Gout
Drug: Placebo
Drug: Allopurinol
Drug: BCX4208
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Multi-center, Placebo-Controlled, Combination Study to Evaluate the Urate-Lowering Activity, Safety, and Potential Pharmacokinetic Interaction of Oral BCX4208 and Allopurinol Administered in Subjects With Gout

Resource links provided by NLM:


Further study details as provided by BioCryst Pharmaceuticals:

Primary Outcome Measures:
  • To estimate the dose response relationship of BCX4208 when administered as a monotherapy and in combination with allopurinol on sUA. [ Time Frame: Day 22 ] [ Designated as safety issue: Yes ]

Enrollment: 87
Study Start Date: May 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: BCX4208 placebo + Allopurinol placebo
Administered daily for 21 days.
Drug: Placebo
Administered daily for 21 days
Active Comparator: BCX4208 placebo + Allopurinol 100mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Active Comparator: BCX4208 placebo + Allopurinol 200 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Active Comparator: BCX4208 Placebo + Allopurinol 300 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Experimental: BCX4208 20 mg + Allopurinol Placebo
Administered daily for 21 days.
Drug: BCX4208
Administered daily for 21 days.
Experimental: BCX4208 20 mg + Allopurinol 100 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 20 mg + Allopurinol 200 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 20 mg + Allopurinol 300 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 40 mg + Allopurinol placebo
Administered daily for 21 days.
Drug: BCX4208
Administered daily for 21 days.
Experimental: BCX4208 40 mg + Allopurinol 100 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 40 mg + Allopurinol 200 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 40 mg + Allopurinol 300 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 80 mg + Allopurinol Placebo
Administered daily for 21 days.
Drug: BCX4208
Administered daily for 21 days.
Experimental: BCX4208 80 mg + Allopurinol 100 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 80 mg + Allopurinol 200 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days
Experimental: BCX4208 80 mg + Allopurinol 300 mg
Administered daily for 21 days.
Drug: Allopurinol
Administered daily for 21 days.
Drug: BCX4208
Adminstered daily for 21 days

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Age ≥18 to <70 years, with screening sUA > 8.0 mg/dL.
  2. Diagnosis of gout according to the criteria of the American Rheumatism Association (1977).
  3. Be willing and able to take colchicine 0.6 mg per day or naproxen 250 mg twice daily (with proton pump inhibitor if needed) as prophylaxis for gout flares.
  4. Be willing to abstain from blood donations from Day -14 to Day 29/Early Termination.
  5. Female participants must be sexually abstinent, sterile, post-menopausal, or on stable contraception.

    • Post-menopausal - females greater ≥ 45 years of age whose last menstrual period, including spotting, was > 1 year ago.
    • Stable contraception - now requires a double barrier method, e.g. condom or diaphragm with spermicide.
  6. Male participants must be abstinent, vasectomized or using condoms with spermicide with partners meeting female requirements.

Exclusion Criteria:

  1. Unable to tolerate allopurinol.
  2. Gout Flare during Screening Period that is resolved less than 2 weeks prior to first treatment.
  3. Unstable angina, history of symptomatic arrhythmia, or Class III or IV heart failure.
  4. ECG Findings: history of congenital long QT syndrome; QTc interval < 350 msec or > 475 msec.
  5. Inadequately controlled hypertension (above either or both 150/95 mm Hg).
  6. Moderate or severe renal impairment and/or calculated creatinine clearance <60 mL/min (using Cockcroft-Gault formula).
  7. ALT or AST > 2.0 x ULN.
  8. CD4+ count by flow cytometry (<500 cells/mm3).
  9. Hgb <12 g/dL or > 17 g/dL (males) or < 11 g/dL or > 16 g/dL (females).
  10. Hct < 37% or > 51% (males) < 33% or > 47% (females).
  11. WBC < 3.7 x 109/L or > 11 x 109/L.
  12. Positive Pregnancy Test.
  13. Females who are pregnant, breastfeeding or planning a pregnancy with the next 4 months.
  14. Positive serology for hepatitis B surface antigen or hepatitis C or HIV type I (HIV Ab).
  15. Immunocompromised or on systemic immunosuppressant medications (including anakinra) within 14 days of study dosing.
  16. Use of azathioprine or 6-mercatopurine within 14 days of study dosing.
  17. Use of HCTZ in doses > 50mg per day within 14 days of study dosing.
  18. Recipient of any live, attenuated vaccine within 6 weeks of Screening.
  19. Receipt of sUA-lowering drugs, ACTH, within 14 days of study dosing.
  20. Use of systemic corticosteroids within 4 weeks prior to study dosing.
  21. Clinically significant and relevant drug allergies.
  22. Chronic or recurrent infections (3 infections at same site) within 12 months.
  23. Cancer within 12 months (except nonmelanomatous localized skin cancer.
  24. Alcohol or drug abuse.
  25. Investigational drug within 30 days of study dosing.
  26. 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: NCT01129648

  Show 18 Study Locations
Sponsors and Collaborators
BioCryst Pharmaceuticals
  More Information

No publications provided

Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01129648     History of Changes
Other Study ID Numbers: BCX4208-202
Study First Received: May 21, 2010
Last Updated: January 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by BioCryst Pharmaceuticals:
Hyperuricemia, gout

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

ClinicalTrials.gov processed this record on October 22, 2014