Trial Outcomes & Findings for Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat (NCT NCT01510769)
NCT ID: NCT01510769
Last Updated: 2016-05-26
Results Overview
Proportion of subjects with an sUA level that is \< 5.0 mg/dL by Month 6
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
330 participants
Primary outcome timeframe
6 months, analysis after all subjects complete 12 months
Results posted on
2016-05-26
Participant Flow
330 participants were randomized and 324 participants were included in the Intent-to-Treat (ITT) population (ie, 6 subjects were randomized but not treated).
Participant milestones
| Measure |
Lesinurad 200 mg + Febuxostat
|
Lesinurad 400 mg + Febuxostat
|
Placebo + Febuxostat
|
|---|---|---|---|
|
Overall Study
STARTED
|
106
|
109
|
109
|
|
Overall Study
COMPLETED
|
79
|
84
|
87
|
|
Overall Study
NOT COMPLETED
|
27
|
25
|
22
|
Reasons for withdrawal
| Measure |
Lesinurad 200 mg + Febuxostat
|
Lesinurad 400 mg + Febuxostat
|
Placebo + Febuxostat
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
7
|
6
|
4
|
|
Overall Study
Gout Flare
|
0
|
3
|
1
|
|
Overall Study
Protocol Violation
|
11
|
10
|
9
|
|
Overall Study
Lost to Follow-up
|
5
|
1
|
5
|
|
Overall Study
Withdrawal by Subject
|
3
|
4
|
3
|
|
Overall Study
Death
|
1
|
1
|
0
|
Baseline Characteristics
Combination Treatment Study in Subjects With Tophaceous Gout With Lesinurad and Febuxostat
Baseline characteristics by cohort
| Measure |
Lesinurad 200 mg + Febuxostat
n=106 Participants
|
Lesinurad 400 mg + Febuxostat
n=109 Participants
|
Placebo + Febuxostat
n=109 Participants
|
Total
n=324 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.2 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
53.3 years
STANDARD_DEVIATION 11.2 • n=7 Participants
|
54.6 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
54.1 years
STANDARD_DEVIATION 11.0 • n=4 Participants
|
|
Age, Customized
<65 Years
|
89 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
268 Participants
n=4 Participants
|
|
Age, Customized
>=65 Years
|
17 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
56 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
100 Participants
n=5 Participants
|
102 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
309 Participants
n=4 Participants
|
|
Region of Enrollment
Australia
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Region of Enrollment
Canada
|
9 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Region of Enrollment
New Zealand
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Region of Enrollment
Switzerland
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
81 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
244 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 6 months, analysis after all subjects complete 12 monthsPopulation: Intent-to-Treat Population
Proportion of subjects with an sUA level that is \< 5.0 mg/dL by Month 6
Outcome measures
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
n=106 Participants
lesinurad 200 mg once daily (qd) plus febuxostat 80 mg
|
Lesinurad 400 mg + Febuxostat 80 mg
n=109 Participants
lesinurad 400 mg qd plus febuxostat 80 mg
|
Placebo + Febuxostat 80 mg
n=109 Participants
placebo qd plus febuxostat 80 mg
|
|---|---|---|---|
|
Subjects With a Serum Urate (sUA) Level That is < 5.0 mg/dL by Month 6
|
0.566 Proportion of Subjects
|
0.761 Proportion of Subjects
|
0.468 Proportion of Subjects
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Intent-to-Treat Population
Proportion of subjects who experience complete resolution of at least 1 target tophus by Month 12
Outcome measures
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
n=106 Participants
lesinurad 200 mg once daily (qd) plus febuxostat 80 mg
|
Lesinurad 400 mg + Febuxostat 80 mg
n=109 Participants
lesinurad 400 mg qd plus febuxostat 80 mg
|
Placebo + Febuxostat 80 mg
n=109 Participants
placebo qd plus febuxostat 80 mg
|
|---|---|---|---|
|
Complete Resolution of at Least One Target Tophus
|
0.255 Proportion of Subjects
|
0.303 Proportion of Subjects
|
0.211 Proportion of Subjects
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Intent-to-Treat Population
Proportion of subjects with a best tophus response on at least 1 target tophus of complete (disappearance of at least 1 target tophus) or partial (≥ 50% decrease in the area of at least 1 target tophus) resolution by Month 12
Outcome measures
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
n=106 Participants
lesinurad 200 mg once daily (qd) plus febuxostat 80 mg
|
Lesinurad 400 mg + Febuxostat 80 mg
n=109 Participants
lesinurad 400 mg qd plus febuxostat 80 mg
|
Placebo + Febuxostat 80 mg
n=109 Participants
placebo qd plus febuxostat 80 mg
|
|---|---|---|---|
|
Complete or Partial Response of at Least One Tophus
|
0.566 Proportion of Subjects
|
0.587 Proportion of Subjects
|
0.505 Proportion of Subjects
|
SECONDARY outcome
Timeframe: 12 MonthsPopulation: Intent-to-Treat Population
Proportion of subjects with an improvement from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at least 0.25 at Month 12. The HAQ-DI assesses a patient's level of functional ability with items scores ranging from 0-3 with 0 being the least disability.
Outcome measures
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
n=77 Participants
lesinurad 200 mg once daily (qd) plus febuxostat 80 mg
|
Lesinurad 400 mg + Febuxostat 80 mg
n=78 Participants
lesinurad 400 mg qd plus febuxostat 80 mg
|
Placebo + Febuxostat 80 mg
n=80 Participants
placebo qd plus febuxostat 80 mg
|
|---|---|---|---|
|
Quality of Life
|
0.442 Proportion of Subjects
|
0.333 Proportion of Subjects
|
0.525 Proportion of Subjects
|
Adverse Events
Lesinurad 200 mg + Febuxostat
Serious events: 6 serious events
Other events: 50 other events
Deaths: 0 deaths
Lesinurad 400 mg + Febuxostat
Serious events: 9 serious events
Other events: 59 other events
Deaths: 0 deaths
Placebo + Febuxostat
Serious events: 10 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lesinurad 200 mg + Febuxostat
n=106 participants at risk
|
Lesinurad 400 mg + Febuxostat
n=109 participants at risk
|
Placebo + Febuxostat
n=109 participants at risk
|
|---|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/106
|
0.92%
1/109 • Number of events 2
|
0.00%
0/109
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.94%
1/106 • Number of events 1
|
0.00%
0/109
|
0.00%
0/109
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Cardiac disorders
Coronary artery disease
|
0.94%
1/106 • Number of events 1
|
0.92%
1/109 • Number of events 2
|
0.00%
0/109
|
|
Cardiac disorders
Pulseless electrical activity
|
0.94%
1/106 • Number of events 1
|
0.00%
0/109
|
0.00%
0/109
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.92%
1/109 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.94%
1/106 • Number of events 1
|
0.00%
0/109
|
0.00%
0/109
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Infections and infestations
Pneumonia
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.94%
1/106 • Number of events 1
|
0.00%
0/109
|
0.00%
0/109
|
|
Musculoskeletal and connective tissue disorders
Joint contracture
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.92%
1/109 • Number of events 1
|
|
Renal and urinary disorders
Renal failure chronic
|
0.00%
0/106
|
0.92%
1/109 • Number of events 1
|
0.00%
0/109
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/106
|
0.00%
0/109
|
0.92%
1/109 • Number of events 1
|
|
Injury, poisoning and procedural complications
Laceration
|
0.94%
1/106 • Number of events 1
|
0.00%
0/109
|
0.00%
0/109
|
Other adverse events
| Measure |
Lesinurad 200 mg + Febuxostat
n=106 participants at risk
|
Lesinurad 400 mg + Febuxostat
n=109 participants at risk
|
Placebo + Febuxostat
n=109 participants at risk
|
|---|---|---|---|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/106
|
2.8%
3/109 • Number of events 3
|
0.00%
0/109
|
|
Gastrointestinal disorders
Toothache
|
0.94%
1/106 • Number of events 1
|
2.8%
3/109 • Number of events 3
|
0.00%
0/109
|
|
General disorders
Non-cardiac chest pain
|
0.94%
1/106 • Number of events 1
|
2.8%
3/109 • Number of events 4
|
0.00%
0/109
|
|
General disorders
Pyrexia
|
0.94%
1/106 • Number of events 1
|
6.4%
7/109 • Number of events 7
|
3.7%
4/109 • Number of events 4
|
|
Infections and infestations
Influenza
|
5.7%
6/106 • Number of events 6
|
1.8%
2/109 • Number of events 4
|
1.8%
2/109 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
9.4%
10/106 • Number of events 10
|
13.8%
15/109 • Number of events 15
|
8.3%
9/109 • Number of events 12
|
|
Injury, poisoning and procedural complications
Contusion
|
1.9%
2/106 • Number of events 2
|
6.4%
7/109 • Number of events 9
|
2.8%
3/109 • Number of events 3
|
|
Injury, poisoning and procedural complications
Excoriation
|
2.8%
3/106 • Number of events 3
|
1.8%
2/109 • Number of events 2
|
0.00%
0/109
|
|
Injury, poisoning and procedural complications
Joint sprain
|
3.8%
4/106 • Number of events 4
|
5.5%
6/109 • Number of events 6
|
1.8%
2/109 • Number of events 2
|
|
Injury, poisoning and procedural complications
Laceration
|
2.8%
3/106 • Number of events 3
|
7.3%
8/109 • Number of events 12
|
3.7%
4/109 • Number of events 5
|
|
Investigations
Blood creatine phosphokinase increased
|
5.7%
6/106 • Number of events 8
|
3.7%
4/109 • Number of events 4
|
2.8%
3/109 • Number of events 3
|
|
Investigations
Blood creatinine increased
|
6.6%
7/106 • Number of events 7
|
7.3%
8/109 • Number of events 11
|
2.8%
3/109 • Number of events 3
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
3.8%
4/106 • Number of events 4
|
0.92%
1/109 • Number of events 1
|
0.92%
1/109 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.5%
8/106 • Number of events 9
|
5.5%
6/109 • Number of events 7
|
4.6%
5/109 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.7%
6/106 • Number of events 9
|
8.3%
9/109 • Number of events 9
|
3.7%
4/109 • Number of events 4
|
|
Nervous system disorders
Headache
|
9.4%
10/106 • Number of events 11
|
5.5%
6/109 • Number of events 7
|
7.3%
8/109 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.8%
4/106 • Number of events 4
|
8.3%
9/109 • Number of events 9
|
2.8%
3/109 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
3.8%
4/106 • Number of events 4
|
0.00%
0/109
|
0.00%
0/109
|
|
Vascular disorders
Hypertension
|
5.7%
6/106 • Number of events 6
|
11.0%
12/109 • Number of events 13
|
7.3%
8/109 • Number of events 8
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER