Bucillamine for the Treatment of Acute Gout Flare in Subjects With Moderate to Severe Gout
Primary Purpose
Gout
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bucillamine
Colchicine
Sponsored by
About this trial
This is an interventional treatment trial for Gout
Eligibility Criteria
Inclusion Criteria:
- Subjects must present with confirmed diagnosis of gout, meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout
- Subjects must have experienced at least one (1) acute gouty arthritic attack in the 12 months prior to randomization
- Presence of acute gout flare for no longer than 3 days at Visit 2
- Pain intensity at inclusion (Visit 2) of 7-10 on 11-point PI-NRS (defined as severe gout flare for this study)
- All patients should not have contraindications for Colchicine use
- Subjects with a history of intolerance to NSAIDs (Checklists Checklist 1)
- Subjects with significant medical contraindication to NSAIDs (Checklist 2)
- Subjects with past failure of NSAIDs to control acute gouty arthritis attacks in the previous 12 months (Checklist 3)
Regarding significant medical contraindication to NSAIDs or past failure of NSAIDs to control acute gouty arthritis attacks in the previous 12 months (i.e. refractoriness to NSAIDs) the patient must meet one of below criteria:
- At least one historical episode within the previous 12 months of being refractory or intolerant to NSAIDs that makes the physician concerned to use NSAIDs for a subsequent acute gout attack
- The current (referring) physician judgment is that NSAIDs are not appropriate for treating the patient's gouty arthritis flare which may be due to changes in patient status such as worsening co-morbid conditions or co-medications (e.g., GI tract disease, renal insufficiency, hypertension, fluid retention, concurrent use of diuretics and/or an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, especially in CKD)
- Subjects must be willing and able to give written informed consent. A HIPAA and/or state privacy consent must also be signed
- Subjects must be able to swallow tablets
- Use of permitted concomitant medications must be unchanged in dose and or frequency, 30 days prior to screening
- Adequate organ function, evidenced by the following laboratory results within 90 days prior to randomization (historical lab results are acceptable).
- Creatine clearance > 45 mL/min based on Cockroft-Gault glomerular filtration rate (GFR) estimation
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of conception.
Exclusion Criteria:
- Subjects with rheumatoid arthritis, psoriatic arthritis, evidence/suspicion of infectious/septic arthritis, acute polyarticular gout (4 or more joints), with arthritis due to any cause other than gout that may confound any study assessments per Investigator discretion
- Subjects who have experienced >2 acute gouty arthritic attacks per month, or >12 attacks overall, in the 6 months prior to randomization
- Subjects with a history of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting within the previous 6 months prior to screening
- Subjects with a Body Mass Index >45 kg/m2; calculated as body weight (kg)/height (m)2 at Screening Visit
- Subjects with acute or chronic infections including known HIV and/or Hepatitis B or C
- Uncontrolled hypertension (>160/90 mmHg seated) (if the first set of BP assessment meets the definition of uncontrolled hypertension, a second set of BP assessments may be performed after the patient has rested for at least 30 min. If the second set of BP assessments does not meet the definition of uncontrolled hypertension the patient will be eligible for participation)
- Subjects with proteinuria ≥1+ or ≥30 mg on dipstick urinalysis that is confirmed on repeat assessment within 24 hours
- Subjects with significant heart failure and activity impairment (Class III-IV of the New York Heart Association (NYHA)
- Subjects with any history of malignancy, 5 years prior to randomization
- Subjects with CKD NKF stages 3B -5 chronic renal dysfunction (eGFR <45 mL/min/1.73m2 acc. to Cockcroft Gault formula)
- Subjects with serious hepatic disorder (Child-Pugh scores B or C)
- Subjects who have not washed out of dopamine antagonists or depleting drugs excluding anticholinergics and/or antihistamines with anticholinergic effects at least 14 days prior to Day 1 (Visit 2)
- Subjects with a documented history of alcohol or substance abuse within the 12 months prior to randomization(consumption of >21 units of alcohol per week is considered alcohol abuse)
- Subjects with significant CNS effects including vertigo and dizziness
Sites / Locations
- West Coast Research
- Texas Physicians Research Medical Group
- Sun Research Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Arm A
Arm B
Arm C
Arm Description
Bucillamine (900 mg total dose over 7 days)
Bucillamine (1,800 mg total dose over 7 days)
Colchicine (1.8 mg total dose in 2 doses taken 1 hour apart)
Outcomes
Primary Outcome Measures
Composite measure of adverse events (AEs), physical examinations, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations, medical history, and prior/concomitant medications
At least a 50% reduction in target joint pain PI-NRS score from baseline without using rescue drug
Secondary Outcome Measures
A greater than or equal to 50% reduction in target joint pain PI-NRS score from baseline at 24 hours and 48 hours post-dose without using rescue drug
Full Information
NCT ID
NCT02330796
First Posted
December 31, 2014
Last Updated
October 4, 2016
Sponsor
Revive Therapeutics, Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT02330796
Brief Title
Bucillamine for the Treatment of Acute Gout Flare in Subjects With Moderate to Severe Gout
Official Title
A RANDOMIZED, MULTICENTRE PHASE IIa OPEN-LABEL, ACTIVE-COMPARATOR TRIAL TO ASSESS THE EFFICACY AND SAFETY OF TWO REGIMENS OF BUCILLAMINE 100 MG TABLETS AS COMPARED TO COLCHICINE 0.6 MG TABLETS FOR THE TREATMENT OF AN ACUTE GOUT FLARE IN SUBJECTS WITH MODERATE TO SEVERE GOUT.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Revive Therapeutics, Ltd.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Phase IIA, open-label, multicenter, active-controlled, parallel-group clinical trial designed to evaluate the safety and efficacy of two doses of Bucillamine compared with low-dose Colchicine in the treatment of patients with acute gout flare.
Detailed Description
To evaluate the safety and tolerability of two regimens of Bucillamine 100 mg (900 mg and 1,800 mg) over seven days of treatment compared with Colchicine 0.6 mg (1.8 mg) in the treatment of patients with acute gout flare
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gout
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Bucillamine (900 mg total dose over 7 days)
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Bucillamine (1,800 mg total dose over 7 days)
Arm Title
Arm C
Arm Type
Active Comparator
Arm Description
Colchicine (1.8 mg total dose in 2 doses taken 1 hour apart)
Intervention Type
Drug
Intervention Name(s)
Bucillamine
Intervention Description
Bucillamine Tablets
Intervention Type
Drug
Intervention Name(s)
Colchicine
Primary Outcome Measure Information:
Title
Composite measure of adverse events (AEs), physical examinations, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations, medical history, and prior/concomitant medications
Time Frame
7 days
Title
At least a 50% reduction in target joint pain PI-NRS score from baseline without using rescue drug
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
A greater than or equal to 50% reduction in target joint pain PI-NRS score from baseline at 24 hours and 48 hours post-dose without using rescue drug
Time Frame
24 hrs and 48 hrs
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects must present with confirmed diagnosis of gout, meeting the American College of Rheumatology (ACR) 1977 preliminary criteria for the classification of acute arthritis of primary gout
Subjects must have experienced at least one (1) acute gouty arthritic attack in the 12 months prior to randomization
Presence of acute gout flare for no longer than 3 days at Visit 2
Pain intensity at inclusion (Visit 2) of 7-10 on 11-point PI-NRS (defined as severe gout flare for this study)
All patients should not have contraindications for Colchicine use
Subjects with a history of intolerance to NSAIDs (Checklists Checklist 1)
Subjects with significant medical contraindication to NSAIDs (Checklist 2)
Subjects with past failure of NSAIDs to control acute gouty arthritis attacks in the previous 12 months (Checklist 3)
Regarding significant medical contraindication to NSAIDs or past failure of NSAIDs to control acute gouty arthritis attacks in the previous 12 months (i.e. refractoriness to NSAIDs) the patient must meet one of below criteria:
At least one historical episode within the previous 12 months of being refractory or intolerant to NSAIDs that makes the physician concerned to use NSAIDs for a subsequent acute gout attack
The current (referring) physician judgment is that NSAIDs are not appropriate for treating the patient's gouty arthritis flare which may be due to changes in patient status such as worsening co-morbid conditions or co-medications (e.g., GI tract disease, renal insufficiency, hypertension, fluid retention, concurrent use of diuretics and/or an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, especially in CKD)
Subjects must be willing and able to give written informed consent. A HIPAA and/or state privacy consent must also be signed
Subjects must be able to swallow tablets
Use of permitted concomitant medications must be unchanged in dose and or frequency, 30 days prior to screening
Adequate organ function, evidenced by the following laboratory results within 90 days prior to randomization (historical lab results are acceptable).
Creatine clearance > 45 mL/min based on Cockroft-Gault glomerular filtration rate (GFR) estimation
For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of conception.
Exclusion Criteria:
Subjects with rheumatoid arthritis, psoriatic arthritis, evidence/suspicion of infectious/septic arthritis, acute polyarticular gout (4 or more joints), with arthritis due to any cause other than gout that may confound any study assessments per Investigator discretion
Subjects who have experienced >2 acute gouty arthritic attacks per month, or >12 attacks overall, in the 6 months prior to randomization
Subjects with a history of myocardial infarction, unstable angina, cerebrovascular events, or coronary artery bypass grafting within the previous 6 months prior to screening
Subjects with a Body Mass Index >45 kg/m2; calculated as body weight (kg)/height (m)2 at Screening Visit
Subjects with acute or chronic infections including known HIV and/or Hepatitis B or C
Uncontrolled hypertension (>160/90 mmHg seated) (if the first set of BP assessment meets the definition of uncontrolled hypertension, a second set of BP assessments may be performed after the patient has rested for at least 30 min. If the second set of BP assessments does not meet the definition of uncontrolled hypertension the patient will be eligible for participation)
Subjects with proteinuria ≥1+ or ≥30 mg on dipstick urinalysis that is confirmed on repeat assessment within 24 hours
Subjects with significant heart failure and activity impairment (Class III-IV of the New York Heart Association (NYHA)
Subjects with any history of malignancy, 5 years prior to randomization
Subjects with CKD NKF stages 3B -5 chronic renal dysfunction (eGFR <45 mL/min/1.73m2 acc. to Cockcroft Gault formula)
Subjects with serious hepatic disorder (Child-Pugh scores B or C)
Subjects who have not washed out of dopamine antagonists or depleting drugs excluding anticholinergics and/or antihistamines with anticholinergic effects at least 14 days prior to Day 1 (Visit 2)
Subjects with a documented history of alcohol or substance abuse within the 12 months prior to randomization(consumption of >21 units of alcohol per week is considered alcohol abuse)
Subjects with significant CNS effects including vertigo and dizziness
Facility Information:
Facility Name
West Coast Research
City
San Roman
State/Province
California
ZIP/Postal Code
94582
Country
United States
Facility Name
Texas Physicians Research Medical Group
City
Arlington
State/Province
Texas
ZIP/Postal Code
76015
Country
United States
Facility Name
Sun Research Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Bucillamine for the Treatment of Acute Gout Flare in Subjects With Moderate to Severe Gout
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