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Combining Lesinurad With Allopurinol in Inadequate Responders (CLEAR 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01493531
Recruitment Status : Completed
First Posted : December 16, 2011
Results First Posted : May 26, 2016
Last Update Posted : May 26, 2016
Sponsor:
Information provided by (Responsible Party):
Ardea Biosciences, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Gout
Interventions Drug: Lesinurad
Drug: Placebo
Drug: Allopurinol
Enrollment 610
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Hide Arm/Group Description lesinurad 200 mg qd plus allopurinol lesinurad 400 mg qd plus allopurinol [Not Specified]
Period Title: Overall Study
Started 204 200 206
Completed 163 150 158
Not Completed 41 50 48
Reason Not Completed
Adverse Event             4             12             9
Gout flare             3             0             2
Protocol Violation             8             15             12
Sponsor terminated study             5             2             3
Lost to Follow-up             5             7             11
Withdrawal by Subject             16             13             11
Death             0             1             0
Arm/Group Title Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol Total
Hide Arm/Group Description lesinurad 200 mg qd plus allopurinol lesinurad 400 mg qd plus allopurinol [Not Specified] Total of all reporting groups
Overall Number of Baseline Participants 204 200 206 610
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 204 participants 200 participants 206 participants 610 participants
51.0  (11.1) 51.3  (11.1) 51.4  (10.6) 51.2  (10.9)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 204 participants 200 participants 206 participants 610 participants
<65 184 175 185 544
>=65 20 25 21 66
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 204 participants 200 participants 206 participants 610 participants
Female
7
   3.4%
6
   3.0%
10
   4.9%
23
   3.8%
Male
197
  96.6%
194
  97.0%
196
  95.1%
587
  96.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 204 participants 200 participants 206 participants 610 participants
Australia 4 9 4 17
Belgium 1 1 2 4
Canada 7 6 12 25
Germany 9 8 8 25
New Zealand 12 7 7 26
Poland 5 11 6 22
South Africa 30 36 33 99
Spain 2 4 2 8
Switzerland 1 0 0 1
Ukraine 25 24 25 74
United States 108 94 107 309
1.Primary Outcome
Title Subjects With a Serum Urate (sUA) < 6.0 mg/dL by Month 6.
Hide Description Proportion of subjects with an sUA level that is < 6.0 mg/dL by Month 6.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population
Arm/Group Title Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Hide Arm/Group Description:
lesinurad 200 mg qd plus allopurinol
lesinurad 400 mg qd plus allopurinol
placebo qd plus allopurinol
Overall Number of Participants Analyzed 204 200 206
Measure Type: Number
Unit of Measure: Proportion of Subjects
0.554 0.665 0.233
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lesinurad 200 mg + Allopurinol, Placebo + Allopurinol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.23 to 0.41
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lesinurad 400 mg + Allopurinol, Placebo + Allopurinol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.34 to 0.52
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.05
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Gout Flares
Hide Description Mean rate of gout flares requiring treatment for the 6-month period from the end of Month 6 to the end of Month 12.
Time Frame 12 Months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Hide Arm/Group Description:
lesinurad 200 mg qd plus allopurinol
lesinurad 400 mg qd plus allopurinol
placebo qd plus allopurinol
Overall Number of Participants Analyzed 204 200 206
Mean (Standard Deviation)
Unit of Measure: Gout Flares
0.7  (1.4) 0.8  (1.7) 0.9  (1.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lesinurad 200 mg + Allopurinol, Placebo + Allopurinol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5716
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.57 to 1.37
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lesinurad 400 mg + Allopurinol, Placebo + Allopurinol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7454
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.60 to 1.45
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Subjects With ≥ 1 Target Tophus at Baseline Who Experience Complete Resolution of at Least 1 Target Tophus by Month 12
Hide Description Proportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Hide Arm/Group Description:
lesinurad 200 mg qd plus allopurinol
lesinurad 400 mg qd plus allopurinol
placebo qd plus allopurinol
Overall Number of Participants Analyzed 35 29 33
Measure Type: Number
Unit of Measure: Proportion of Subjects
0.314 0.276 0.333
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lesinurad 200 mg + Allopurinol, Placebo + Allopurinol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8466
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.24 to 0.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lesinurad 400 mg + Allopurinol, Placebo + Allopurinol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6301
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.29 to 0.17
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Hide Arm/Group Description lesinurad 200 mg qd plus allopurinol lesinurad 400 mg qd plus allopurinol [Not Specified]
All-Cause Mortality
Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/204 (4.41%)      19/200 (9.50%)      8/206 (3.88%)    
Cardiac disorders       
Coronary artery disease  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Myocardial infarction  1  0/204 (0.00%)  0 3/200 (1.50%)  3 0/206 (0.00%)  0
Atrial fibrillation  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Intracardiac thrombus  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Gastrointestinal disorders       
Duodenal ulcer haemorrhage  1  0/204 (0.00%)  0 1/200 (0.50%)  1 1/206 (0.49%)  1
Gastrointestinal haemorrhage  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
General disorders       
Adverse drug reaction  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Non-cardiac chest pain  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Infections and infestations       
Pneumonia  1  2/204 (0.98%)  2 0/200 (0.00%)  0 0/206 (0.00%)  0
Bronchopneumonia  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Cellulitis  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Empyema  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Pyelonephritis chronic  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Sinobronchitis  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Abscess limb  1  0/204 (0.00%)  0 0/200 (0.00%)  0 1/206 (0.49%)  1
Appendicitis  1  0/204 (0.00%)  0 0/200 (0.00%)  0 1/206 (0.49%)  1
Diverticulitis  1  0/204 (0.00%)  0 0/200 (0.00%)  0 1/206 (0.49%)  1
Injury, poisoning and procedural complications       
Multiple drug overdose  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Multiple injuries  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Femur fracture  1  0/204 (0.00%)  0 0/200 (0.00%)  0 1/206 (0.49%)  1
Metabolism and nutrition disorders       
Gout  1  0/204 (0.00%)  0 2/200 (1.00%)  4 0/206 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Osteoarthritis  1  0/204 (0.00%)  0 2/200 (1.00%)  2 0/206 (0.00%)  0
Arthralgia  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Back pain  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Flank pain  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Intervertebral disc degeneration  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Gastric cancer  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Ovarian adenoma  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Parathyroid tumour benign  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Prostate cancer  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Pancreatic neuroendocrine tumour  1  0/204 (0.00%)  0 0/200 (0.00%)  0 1/206 (0.49%)  1
Nervous system disorders       
Subarachnoid haemorrhage  1  0/204 (0.00%)  0 0/200 (0.00%)  0 1/206 (0.49%)  1
Psychiatric disorders       
Depression  1  1/204 (0.49%)  1 0/200 (0.00%)  0 0/206 (0.00%)  0
Dissociative disorder  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Renal and urinary disorders       
Nephrolithiasis  1  0/204 (0.00%)  0 2/200 (1.00%)  2 0/206 (0.00%)  0
Renal failure acute  1  0/204 (0.00%)  0 1/200 (0.50%)  1 1/206 (0.49%)  1
Renal impairment  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pulmonary oedema  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Vascular disorders       
Hypertensive crisis  1  0/204 (0.00%)  0 1/200 (0.50%)  1 0/206 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.02%
Lesinurad 200 mg + Allopurinol Lesinurad 400 mg + Allopurinol Placebo + Allopurinol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   85/204 (41.67%)      82/200 (41.00%)      60/206 (29.13%)    
Gastrointestinal disorders       
Diarrhoea  1  10/204 (4.90%)  13 14/200 (7.00%)  21 7/206 (3.40%)  8
Gastrooesophageal reflux disease  1  10/204 (4.90%)  10 4/200 (2.00%)  4 1/206 (0.49%)  1
Infections and infestations       
Upper respiratory tract infection  1  14/204 (6.86%)  16 30/200 (15.00%)  39 21/206 (10.19%)  23
Influenza  1  14/204 (6.86%)  17 8/200 (4.00%)  9 4/206 (1.94%)  4
Bronchitis  1  9/204 (4.41%)  9 4/200 (2.00%)  4 4/206 (1.94%)  5
Injury, poisoning and procedural complications       
Joint sprain  1  9/204 (4.41%)  9 2/200 (1.00%)  2 4/206 (1.94%)  4
Investigations       
Blood creatinine increased  1  8/204 (3.92%)  9 19/200 (9.50%)  24 7/206 (3.40%)  7
Musculoskeletal and connective tissue disorders       
Arthralgia  1  24/204 (11.76%)  24 6/200 (3.00%)  7 9/206 (4.37%)  14
Nervous system disorders       
Headache  1  10/204 (4.90%)  11 12/200 (6.00%)  13 8/206 (3.88%)  8
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  5/204 (2.45%)  5 1/200 (0.50%)  1 0/206 (0.00%)  0
Vascular disorders       
Hypertension  1  17/204 (8.33%)  17 16/200 (8.00%)  16 10/206 (4.85%)  10
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI shall submit a copy of the Publication to Sponsor for review at least 45 days prior to its proposed submission. Sponsor reserves the right to delay any such publication for an additional period of 60 days. Upon Sponsor's request, PI agrees to delete from the proposed publication any Confidential Information. PI agrees not to release any publication without the prior written permission of Sponsor.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Nihar Bhakta, MD
Organization: Ardea Biosciences, Inc.
Phone: 1-858-652-6671
EMail: nbhakta@ardeabio.com
Layout table for additonal information
Responsible Party: Ardea Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01493531     History of Changes
Other Study ID Numbers: RDEA594-302
2011-003767-29 ( EudraCT Number )
First Submitted: December 13, 2011
First Posted: December 16, 2011
Results First Submitted: January 14, 2016
Results First Posted: May 26, 2016
Last Update Posted: May 26, 2016