Trial Outcomes & Findings for Lesinurad and Febuxostat Combination Extension Study in Gout (NCT NCT01808144)
NCT ID: NCT01808144
Last Updated: 2018-01-30
Results Overview
Percentage of participants in Study 307 With sUA \< 5.0 mg/dL from the Core Studies 304 and Extension Study 307 - Observed Cases
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
196 participants
Primary outcome timeframe
Up to approximately 2.5 years (at Extension Month 12)
Results posted on
2018-01-30
Participant Flow
Subjects entered this extension Study RDEA594-307 while the core Study RDEA594-304 was ongoing and the database was not yet locked. To maintain the blind of the core study for subjects entering the extension, the lesinurad dose for all subjects in this extension study was blinded to the Sponsor until database lock of Study RDEA594-304.
Subjects randomized to lesinurad (RDEA594) 200 mg or 400 mg + febuxostat (FBX) 80 mg in Study RDEA594-304 continued to receive the same dose in this study. Subjects randomized to placebo + febuxostat 80 mg in Study RDEA594-304 were randomized in a double-blind, 1:1 fashion to either lesinurad 200 mg or 400 mg + febuxostat 80 mg.
Participant milestones
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
|
Lesinurad 400 mg + Febuxostat 80 mg
|
|---|---|---|
|
Overall Study
STARTED
|
97
|
99
|
|
Overall Study
COMPLETED
|
57
|
51
|
|
Overall Study
NOT COMPLETED
|
40
|
48
|
Reasons for withdrawal
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
|
Lesinurad 400 mg + Febuxostat 80 mg
|
|---|---|---|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
16
|
23
|
|
Overall Study
Lost to Follow-up
|
6
|
3
|
|
Overall Study
Protocol Violation
|
6
|
6
|
|
Overall Study
Gout flare
|
0
|
1
|
|
Overall Study
Adverse Event
|
11
|
15
|
Baseline Characteristics
Lesinurad and Febuxostat Combination Extension Study in Gout
Baseline characteristics by cohort
| Measure |
Lesinurad 400 mg + Febuxostat 80 mg
n=99 Participants
|
Lesinurad 200 mg + Febuxostat 80 mg
n=97 Participants
|
Total
n=196 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.1 Years
STANDARD_DEVIATION 10.58 • n=5 Participants
|
52.9 Years
STANDARD_DEVIATION 10.24 • n=7 Participants
|
52.5 Years
STANDARD_DEVIATION 10.41 • n=5 Participants
|
|
Age, Customized
< 65 years
|
88 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
175 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
7 Participant
n=5 Participants
|
1 Participant
n=7 Participants
|
8 Participant
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
92 Participant
n=5 Participants
|
96 Participant
n=7 Participants
|
188 Participant
n=5 Participants
|
|
Region of Enrollment
United States
|
72 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
144 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Region of Enrollment
Switzerland
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 2.5 years (at Extension Month 12)Population: Number of Participants Analyzed for this Outcome Measure reflects the number of participants who completed Extension Month 12.
Percentage of participants in Study 307 With sUA \< 5.0 mg/dL from the Core Studies 304 and Extension Study 307 - Observed Cases
Outcome measures
| Measure |
Lesinurad 400 mg + Febuxostat 80 mg
n=80 Participants
|
Lesinurad 200 mg + Febuxostat 80 mg
n=72 Participants
|
|---|---|---|
|
Percentage of Participants With an sUA Level That is < 5.0 mg/dL
|
82.5 Percentage of participants
|
77.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to approximatley 2.5 years (at Extension Month 12)Population: ITT Population Number of Participants Analyzed for this Outcome Measure reflects the number of participants who completed through Month 12.
Percentage of participants (With at Least One Target Tophus at Baseline) Who Experience Complete Resolution of at Least One Target Tophus During the Core and Extension Studies at Extension Month 12 (Observed Cases)
Outcome measures
| Measure |
Lesinurad 400 mg + Febuxostat 80 mg
n=77 Participants
|
Lesinurad 200 mg + Febuxostat 80 mg
n=70 Participants
|
|---|---|---|
|
Percentage of Participants (With at Least One Target Tophus at Baseline) Who Experience Complete Resolution of at Least One Target Tophus
|
61.0 Percentage of participants
|
54.3 Percentage of participants
|
Adverse Events
Lesinurad 200 mg + Febuxostat 80 mg
Serious events: 16 serious events
Other events: 61 other events
Deaths: 1 deaths
Lesinurad 400 mg + Febuxostat 80 mg
Serious events: 19 serious events
Other events: 70 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
n=97 participants at risk
|
Lesinurad 400 mg + Febuxostat 80 mg
n=99 participants at risk
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
2.1%
2/97 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Cellulitis
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Device related infection
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Diverticulitis
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Localised infection
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Urosepsis
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Blood and lymphatic system disorders
Anaemia
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Metabolism and nutrition disorders
Gout
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Psychiatric disorders
Depression
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Nervous system disorders
Cerebrovascular accident
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Nervous system disorders
Syncope
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Cardiac disorders
Atrial fibrillation
|
2.1%
2/97 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Cardiac disorders
Cardiac failure
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Vascular disorders
Hypertension
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Hepatobiliary disorders
Cholecystitis
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Joint destruction
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Renal and urinary disorders
Renal impairment
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Renal and urinary disorders
Stag horn calculus
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
Other adverse events
| Measure |
Lesinurad 200 mg + Febuxostat 80 mg
n=97 participants at risk
|
Lesinurad 400 mg + Febuxostat 80 mg
n=99 participants at risk
|
|---|---|---|
|
Investigations
Blood creatinine increased
|
11.3%
11/97 • Number of events 14 • Up to approximately 2.5 years (at Extension Month 12)
|
13.1%
13/99 • Number of events 15 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Nasopharyngitis
|
6.2%
6/97 • Number of events 6 • Up to approximately 2.5 years (at Extension Month 12)
|
14.1%
14/99 • Number of events 20 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Vascular disorders
Hypertension
|
6.2%
6/97 • Number of events 6 • Up to approximately 2.5 years (at Extension Month 12)
|
10.1%
10/99 • Number of events 10 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Bronchitis
|
11.3%
11/97 • Number of events 12 • Up to approximately 2.5 years (at Extension Month 12)
|
4.0%
4/99 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Upper respiratory tract infection
|
8.2%
8/97 • Number of events 10 • Up to approximately 2.5 years (at Extension Month 12)
|
6.1%
6/99 • Number of events 9 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Sinusitis
|
8.2%
8/97 • Number of events 8 • Up to approximately 2.5 years (at Extension Month 12)
|
5.1%
5/99 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Nervous system disorders
Headache
|
5.2%
5/97 • Number of events 6 • Up to approximately 2.5 years (at Extension Month 12)
|
7.1%
7/99 • Number of events 9 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
6/97 • Number of events 10 • Up to approximately 2.5 years (at Extension Month 12)
|
5.1%
5/99 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Urinary tract infection
|
6.2%
6/97 • Number of events 11 • Up to approximately 2.5 years (at Extension Month 12)
|
5.1%
5/99 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.1%
4/97 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
6.1%
6/99 • Number of events 11 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
5.2%
5/97 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
4.0%
4/99 • Number of events 4 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Gastrointestinal disorders
Toothache
|
4.1%
4/97 • Number of events 4 • Up to approximately 2.5 years (at Extension Month 12)
|
5.1%
5/99 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Investigations
Creatinine renal clearance decreased
|
5.2%
5/97 • Number of events 6 • Up to approximately 2.5 years (at Extension Month 12)
|
3.0%
3/99 • Number of events 3 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
6.1%
6/99 • Number of events 7 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.2%
5/97 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.1%
2/97 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
4.0%
4/99 • Number of events 6 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.2%
5/97 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
1.0%
1/99 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Influenza
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
6.1%
6/99 • Number of events 7 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
6.1%
6/99 • Number of events 6 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Injury, poisoning and procedural complications
Muscle strain
|
6.2%
6/97 • Number of events 7 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
3.1%
3/97 • Number of events 3 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Cellulitis
|
3.1%
3/97 • Number of events 3 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
5.1%
5/99 • Number of events 6 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.1%
2/97 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
3.0%
3/99 • Number of events 3 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Investigations
C-reactive protein increased
|
2.1%
2/97 • Number of events 3 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
General disorders
Influenza like illness
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
4.0%
4/99 • Number of events 4 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Psychiatric disorders
Insomnia
|
4.1%
4/97 • Number of events 4 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
4.0%
4/99 • Number of events 4 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Gastrointestinal disorders
Nausea
|
2.1%
2/97 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Investigations
Liver function test abnormal
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
General disorders
Pyrexia
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
3.0%
3/99 • Number of events 5 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Tooth abscess
|
1.0%
1/97 • Number of events 1 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 3 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
2.1%
2/97 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
0.00%
0/99 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/97 • Up to approximately 2.5 years (at Extension Month 12)
|
2.0%
2/99 • Number of events 2 • Up to approximately 2.5 years (at Extension Month 12)
|
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