Trial Outcomes & Findings for Combining Lesinurad With Allopurinol in Inadequate Responders (NCT NCT01493531)
NCT ID: NCT01493531
Last Updated: 2016-05-26
Results Overview
Proportion of subjects with an sUA level that is \< 6.0 mg/dL by Month 6.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
610 participants
Primary outcome timeframe
6 months
Results posted on
2016-05-26
Participant Flow
Participant milestones
| Measure |
Lesinurad 200 mg + Allopurinol
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
|
|---|---|---|---|
|
Overall Study
STARTED
|
204
|
200
|
206
|
|
Overall Study
COMPLETED
|
163
|
150
|
158
|
|
Overall Study
NOT COMPLETED
|
41
|
50
|
48
|
Reasons for withdrawal
| Measure |
Lesinurad 200 mg + Allopurinol
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
12
|
9
|
|
Overall Study
Gout flare
|
3
|
0
|
2
|
|
Overall Study
Protocol Violation
|
8
|
15
|
12
|
|
Overall Study
Sponsor terminated study
|
5
|
2
|
3
|
|
Overall Study
Lost to Follow-up
|
5
|
7
|
11
|
|
Overall Study
Withdrawal by Subject
|
16
|
13
|
11
|
|
Overall Study
Death
|
0
|
1
|
0
|
Baseline Characteristics
Combining Lesinurad With Allopurinol in Inadequate Responders
Baseline characteristics by cohort
| Measure |
Lesinurad 200 mg + Allopurinol
n=204 Participants
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
n=200 Participants
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
n=206 Participants
|
Total
n=610 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
51.0 years
STANDARD_DEVIATION 11.1 • n=39 Participants
|
51.3 years
STANDARD_DEVIATION 11.1 • n=41 Participants
|
51.4 years
STANDARD_DEVIATION 10.6 • n=35 Participants
|
51.2 years
STANDARD_DEVIATION 10.9 • n=31 Participants
|
|
Age, Customized
<65
|
184 Participants
n=39 Participants
|
175 Participants
n=41 Participants
|
185 Participants
n=35 Participants
|
544 Participants
n=31 Participants
|
|
Age, Customized
>=65
|
20 Participants
n=39 Participants
|
25 Participants
n=41 Participants
|
21 Participants
n=35 Participants
|
66 Participants
n=31 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
23 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
197 Participants
n=39 Participants
|
194 Participants
n=41 Participants
|
196 Participants
n=35 Participants
|
587 Participants
n=31 Participants
|
|
Region of Enrollment
Australia
|
4 Participants
n=39 Participants
|
9 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
17 Participants
n=31 Participants
|
|
Region of Enrollment
Belgium
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
4 Participants
n=31 Participants
|
|
Region of Enrollment
Canada
|
7 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
12 Participants
n=35 Participants
|
25 Participants
n=31 Participants
|
|
Region of Enrollment
Germany
|
9 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
8 Participants
n=35 Participants
|
25 Participants
n=31 Participants
|
|
Region of Enrollment
New Zealand
|
12 Participants
n=39 Participants
|
7 Participants
n=41 Participants
|
7 Participants
n=35 Participants
|
26 Participants
n=31 Participants
|
|
Region of Enrollment
Poland
|
5 Participants
n=39 Participants
|
11 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
22 Participants
n=31 Participants
|
|
Region of Enrollment
South Africa
|
30 Participants
n=39 Participants
|
36 Participants
n=41 Participants
|
33 Participants
n=35 Participants
|
99 Participants
n=31 Participants
|
|
Region of Enrollment
Spain
|
2 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
8 Participants
n=31 Participants
|
|
Region of Enrollment
Switzerland
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
|
Region of Enrollment
Ukraine
|
25 Participants
n=39 Participants
|
24 Participants
n=41 Participants
|
25 Participants
n=35 Participants
|
74 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
108 Participants
n=39 Participants
|
94 Participants
n=41 Participants
|
107 Participants
n=35 Participants
|
309 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Intent-to-Treat Population
Proportion of subjects with an sUA level that is \< 6.0 mg/dL by Month 6.
Outcome measures
| Measure |
Lesinurad 200 mg + Allopurinol
n=204 Participants
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
n=200 Participants
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
n=206 Participants
placebo qd plus allopurinol
|
|---|---|---|---|
|
Subjects With a Serum Urate (sUA) < 6.0 mg/dL by Month 6.
|
0.554 Proportion of Subjects
|
0.665 Proportion of Subjects
|
0.233 Proportion of Subjects
|
SECONDARY outcome
Timeframe: 12 MonthsMean rate of gout flares requiring treatment for the 6-month period from the end of Month 6 to the end of Month 12.
Outcome measures
| Measure |
Lesinurad 200 mg + Allopurinol
n=204 Participants
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
n=200 Participants
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
n=206 Participants
placebo qd plus allopurinol
|
|---|---|---|---|
|
Gout Flares
|
0.7 Gout Flares
Standard Deviation 1.4
|
0.8 Gout Flares
Standard Deviation 1.7
|
0.9 Gout Flares
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: 12 monthsProportion of subjects with ≥ 1 target tophus at Baseline who experience complete resolution of at least 1 target tophus by Month 12
Outcome measures
| Measure |
Lesinurad 200 mg + Allopurinol
n=35 Participants
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
n=29 Participants
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
n=33 Participants
placebo qd plus allopurinol
|
|---|---|---|---|
|
Subjects With ≥ 1 Target Tophus at Baseline Who Experience Complete Resolution of at Least 1 Target Tophus by Month 12
|
0.314 Proportion of Subjects
|
0.276 Proportion of Subjects
|
0.333 Proportion of Subjects
|
Adverse Events
Lesinurad 200 mg + Allopurinol
Serious events: 9 serious events
Other events: 85 other events
Deaths: 0 deaths
Lesinurad 400 mg + Allopurinol
Serious events: 19 serious events
Other events: 82 other events
Deaths: 0 deaths
Placebo + Allopurinol
Serious events: 8 serious events
Other events: 60 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lesinurad 200 mg + Allopurinol
n=204 participants at risk
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
n=200 participants at risk
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
n=206 participants at risk
|
|---|---|---|---|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Infections and infestations
Pneumonia
|
0.98%
2/204 • Number of events 2
|
0.00%
0/200
|
0.00%
0/206
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Infections and infestations
Cellulitis
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Infections and infestations
Empyema
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Infections and infestations
Pyelonephritis chronic
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Infections and infestations
Sinobronchitis
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Infections and infestations
Abscess limb
|
0.00%
0/204
|
0.00%
0/200
|
0.49%
1/206 • Number of events 1
|
|
Infections and infestations
Appendicitis
|
0.00%
0/204
|
0.00%
0/200
|
0.49%
1/206 • Number of events 1
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/204
|
0.00%
0/200
|
0.49%
1/206 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian adenoma
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Parathyroid tumour benign
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neuroendocrine tumour
|
0.00%
0/204
|
0.00%
0/200
|
0.49%
1/206 • Number of events 1
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/204
|
1.0%
2/200 • Number of events 4
|
0.00%
0/206
|
|
Psychiatric disorders
Depression
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Psychiatric disorders
Dissociative disorder
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/204
|
0.00%
0/200
|
0.49%
1/206 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/204
|
1.5%
3/200 • Number of events 3
|
0.00%
0/206
|
|
Cardiac disorders
Atrial fibrillation
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Cardiac disorders
Intracardiac thrombus
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Gastrointestinal disorders
Duodenal ulcer haemorrhage
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.49%
1/206 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/204
|
1.0%
2/200 • Number of events 2
|
0.00%
0/206
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/204
|
1.0%
2/200 • Number of events 2
|
0.00%
0/206
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.49%
1/206 • Number of events 1
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/204
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
General disorders
Adverse drug reaction
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
General disorders
Non-cardiac chest pain
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Injury, poisoning and procedural complications
Multiple drug overdose
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.49%
1/204 • Number of events 1
|
0.00%
0/200
|
0.00%
0/206
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/204
|
0.00%
0/200
|
0.49%
1/206 • Number of events 1
|
Other adverse events
| Measure |
Lesinurad 200 mg + Allopurinol
n=204 participants at risk
lesinurad 200 mg qd plus allopurinol
|
Lesinurad 400 mg + Allopurinol
n=200 participants at risk
lesinurad 400 mg qd plus allopurinol
|
Placebo + Allopurinol
n=206 participants at risk
|
|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
6.9%
14/204 • Number of events 16
|
15.0%
30/200 • Number of events 39
|
10.2%
21/206 • Number of events 23
|
|
Infections and infestations
Influenza
|
6.9%
14/204 • Number of events 17
|
4.0%
8/200 • Number of events 9
|
1.9%
4/206 • Number of events 4
|
|
Infections and infestations
Bronchitis
|
4.4%
9/204 • Number of events 9
|
2.0%
4/200 • Number of events 4
|
1.9%
4/206 • Number of events 5
|
|
Nervous system disorders
Headache
|
4.9%
10/204 • Number of events 11
|
6.0%
12/200 • Number of events 13
|
3.9%
8/206 • Number of events 8
|
|
Vascular disorders
Hypertension
|
8.3%
17/204 • Number of events 17
|
8.0%
16/200 • Number of events 16
|
4.9%
10/206 • Number of events 10
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.5%
5/204 • Number of events 5
|
0.50%
1/200 • Number of events 1
|
0.00%
0/206
|
|
Gastrointestinal disorders
Diarrhoea
|
4.9%
10/204 • Number of events 13
|
7.0%
14/200 • Number of events 21
|
3.4%
7/206 • Number of events 8
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
4.9%
10/204 • Number of events 10
|
2.0%
4/200 • Number of events 4
|
0.49%
1/206 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.8%
24/204 • Number of events 24
|
3.0%
6/200 • Number of events 7
|
4.4%
9/206 • Number of events 14
|
|
Investigations
Blood creatinine increased
|
3.9%
8/204 • Number of events 9
|
9.5%
19/200 • Number of events 24
|
3.4%
7/206 • Number of events 7
|
|
Injury, poisoning and procedural complications
Joint sprain
|
4.4%
9/204 • Number of events 9
|
1.0%
2/200 • Number of events 2
|
1.9%
4/206 • Number of events 4
|
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