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

Primary Purpose

Gout

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Allopurinol
Allopurinol
Allopurinol
BCX4208
Allopurinol
Allopurinol
Allopurinol
BCX4208
Allopurinol
Allopurinol
Allopurinol
BCX4208
Allopurinol
Allopurinol
Allopurinol
BCX4208
Sponsored by
BioCryst Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gout focused on measuring Hyperuricemia, gout

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Active Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

BCX4208 placebo + Allopurinol placebo

BCX4208 placebo + Allopurinol 100mg

BCX4208 placebo + Allopurinol 200 mg

BCX4208 Placebo + Allopurinol 300 mg

BCX4208 20 mg + Allopurinol Placebo

BCX4208 20 mg + Allopurinol 100 mg

BCX4208 20 mg + Allopurinol 200 mg

BCX4208 20 mg + Allopurinol 300 mg

BCX4208 40 mg + Allopurinol placebo

BCX4208 40 mg + Allopurinol 100 mg

BCX4208 40 mg + Allopurinol 200 mg

BCX4208 40 mg + Allopurinol 300 mg

BCX4208 80 mg + Allopurinol Placebo

BCX4208 80 mg + Allopurinol 100 mg

BCX4208 80 mg + Allopurinol 200 mg

BCX4208 80 mg + Allopurinol 300 mg

Arm Description

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Administered daily for 21 days.

Outcomes

Primary Outcome Measures

To estimate the dose response relationship of BCX4208 when administered as a monotherapy and in combination with allopurinol on sUA.

Secondary Outcome Measures

Full Information

First Posted
May 21, 2010
Last Updated
January 18, 2012
Sponsor
BioCryst Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01129648
Brief Title
Study to Evaluate sUA-Lowering Activity, Safety & PK Interaction of Oral BCX4208 & Allopurinol Admin. in Subjects w/Gout
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BioCryst Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
To evaluate safety and efficacy of BCX4208 alone and in combination with allopurinol in subjects with gout.
Detailed Description
This study is a Phase 2, randomized, double-blind, multi-center, placebo-controlled study to evaluate efficacy and safety of BCX4208 alone and in combination with allopurinol in approximately 80 subjects with gout. The study is a factorial design, evaluating doses of BCX4208 previously found to be safe and well-tolerated in healthy subjects and subjects with psoriasis and gout. Doses of allopurinol are according to package insert recommendations. Approximately 80 subjects will be randomized equally to one of 16 treatment groups. The study will consist of 3 periods: the Screening Period, the Treatment Period, and the Follow-Up Period. The Screening period will be conducted within Day -30 to Day -1, as long as all inclusion and exclusion criteria are satisfied (see Section 8). For subjects receiving urate-lowering therapy; these subjects must discontinue the urate-lowering therapy by Day -14 to assure a washout period of at least 14 days before entering the Treatment Period. Some Screening procedures such as a recording of medical history and clinical laboratory tests performed at Screening only may be performed at any time during the Screening Period (Day -30 to Day -1). Other Screening procedures must be performed within the 7 days prior to the first dose of study drug (i.e., from Day -7 to Day -1); these include: physical examination, height, weight, clinical chemistry (including baseline and qualifying sUA), hematology, and urinalysis evaluations, CD4+, CD8+, CD20+, and CD56+ lymphocyte counts, a serum pregnancy test in females of child-bearing potential, 12-lead ECG, and vital signs assessments. An otherwise qualified subject may have up to 2 repeated determinations of sUA and/or lymphocyte subsets assayed to meet the entry criteria for this study, as long as the qualifying sUA and lymphocyte subsets assays occur 7 or fewer days prior to the first dose of study drug. These assessments will constitute the Baseline assessments for the purpose of comparisons with these same assessments post-dose. Gout flare prophylaxis with colchicine or naproxen is required to be started prior to the first dose of study drug. Colchicine 0.6 mg once a day will begin at least 7 days prior to Day 1, or naproxen 250 mg twice daily will be started at least 48 hours prior to Day 1. For subjects who discontinue urate-lowering therapy, the required gout flare prophylaxis will begin at or before the cessation of the urate-lowering therapy. A recording of concomitant medications and AEs will take place from the time of the signing of the Informed Consent Form (ICF) and throughout the duration of the study. The Treatment Period begins on Day 1. Subjects are to arrive at the study clinic on Day 1 after an overnight fast. After a final review of eligibility criteria, pre-dose vital signs assessments, and BCX4208, allopurinol, and oxypurinol PK blood draw have been performed, subjects will be randomized and administered the first dose of study drug. Subjects will remain in the study clinic for Hour 2, Hour 4, and Hour 8 PK sampling and will return to the study clinic for efficacy and safety evaluations prior to dosing on Days 2, 8, and 15. Subjects will take study drug daily from Day 1 to Day 21, so that the Day 22 evaluation will occur approximately 24 hours after the last dose of study drug. After the Day 22 evaluation, subjects will enter the Follow-Up Period and will return to the study clinic on Day 29 for safety evaluation. Subjects may resume their prior urate-lowering therapy after the assessments on Day 29. Subjects who on Day 29 have unresolved treatment-emergent AEs will be followed beyond Day 29 until either resolution of the AE or until clinically stable. This subset of subjects will conclude their study participation at the Day 50 Telephone Safety Follow-Up Contact. Efficacy will be assessed during the study by means of sUA concentrations. Safety will be assessed during the study by means of physical examination, weight, clinical chemistry, hematology, and urinalysis parameters, absolute CD4+, CD8+, CD20+, and CD56+ lymphocyte counts, 12-lead ECG, vital signs assessments, and AE assessments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout
Keywords
Hyperuricemia, gout

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BCX4208 placebo + Allopurinol placebo
Arm Type
Placebo Comparator
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 placebo + Allopurinol 100mg
Arm Type
Active Comparator
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 placebo + Allopurinol 200 mg
Arm Type
Active Comparator
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 Placebo + Allopurinol 300 mg
Arm Type
Active Comparator
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 20 mg + Allopurinol Placebo
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 20 mg + Allopurinol 100 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 20 mg + Allopurinol 200 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 20 mg + Allopurinol 300 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 40 mg + Allopurinol placebo
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 40 mg + Allopurinol 100 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 40 mg + Allopurinol 200 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 40 mg + Allopurinol 300 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 80 mg + Allopurinol Placebo
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 80 mg + Allopurinol 100 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 80 mg + Allopurinol 200 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Arm Title
BCX4208 80 mg + Allopurinol 300 mg
Arm Type
Experimental
Arm Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered daily for 21 days
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
BCX4208
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
BCX4208
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
BCX4208
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Intervention Description
Administered daily for 21 days.
Intervention Type
Drug
Intervention Name(s)
BCX4208
Intervention Description
Adminstered daily for 21 days
Primary Outcome Measure Information:
Title
To estimate the dose response relationship of BCX4208 when administered as a monotherapy and in combination with allopurinol on sUA.
Time Frame
Day 22

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 to <70 years, with screening sUA > 8.0 mg/dL. Diagnosis of gout according to the criteria of the American Rheumatism Association (1977). 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. Be willing to abstain from blood donations from Day -14 to Day 29/Early Termination. 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. Male participants must be abstinent, vasectomized or using condoms with spermicide with partners meeting female requirements. Exclusion Criteria: Unable to tolerate allopurinol. Gout Flare during Screening Period that is resolved less than 2 weeks prior to first treatment. Unstable angina, history of symptomatic arrhythmia, or Class III or IV heart failure. ECG Findings: history of congenital long QT syndrome; QTc interval < 350 msec or > 475 msec. Inadequately controlled hypertension (above either or both 150/95 mm Hg). Moderate or severe renal impairment and/or calculated creatinine clearance <60 mL/min (using Cockcroft-Gault formula). ALT or AST > 2.0 x ULN. CD4+ count by flow cytometry (<500 cells/mm3). Hgb <12 g/dL or > 17 g/dL (males) or < 11 g/dL or > 16 g/dL (females). Hct < 37% or > 51% (males) < 33% or > 47% (females). WBC < 3.7 x 109/L or > 11 x 109/L. Positive Pregnancy Test. Females who are pregnant, breastfeeding or planning a pregnancy with the next 4 months. Positive serology for hepatitis B surface antigen or hepatitis C or HIV type I (HIV Ab). Immunocompromised or on systemic immunosuppressant medications (including anakinra) within 14 days of study dosing. Use of azathioprine or 6-mercatopurine within 14 days of study dosing. Use of HCTZ in doses > 50mg per day within 14 days of study dosing. Recipient of any live, attenuated vaccine within 6 weeks of Screening. Receipt of sUA-lowering drugs, ACTH, within 14 days of study dosing. Use of systemic corticosteroids within 4 weeks prior to study dosing. Clinically significant and relevant drug allergies. Chronic or recurrent infections (3 infections at same site) within 12 months. Cancer within 12 months (except nonmelanomatous localized skin cancer. Alcohol or drug abuse. Investigational drug within 30 days of study dosing. 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.
Facility Information:
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
City
Irvine
State/Province
California
ZIP/Postal Code
92618
Country
United States
City
South Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96814
Country
United States
City
Boise
State/Province
Idaho
ZIP/Postal Code
83704
Country
United States
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40504
Country
United States
City
Frederick
State/Province
Maryland
ZIP/Postal Code
21702
Country
United States
City
Olive Branch
State/Province
Mississippi
ZIP/Postal Code
38654
Country
United States
City
Billings
State/Province
Montana
ZIP/Postal Code
59107
Country
United States
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68134
Country
United States
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28211
Country
United States
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57702
Country
United States
City
Bristol
State/Province
Tennessee
ZIP/Postal Code
37620
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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