GoutPhase 2RDEA594-203NCT01001338
Allopurinol Combination Study
A Phase 2 study testing RDEA594 and Allopurinol in people with Gout, run by Ardea Biosciences, Inc. at 44 sites in 6 countries.
Trial summary
To compare the proportion of subjects whose serum urate (sUA) levels are < 6.0 mg/dL following 4 weeks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response with standard doses of allopurinol. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Gout
- What is being tested?
- RDEA594 and Allopurinol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 227 participants
- Where
- 44 sitesin 6 countries
- Study dates
- Oct 2009to Aug 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or a post-menopausal or surgically sterile female.
- 18 - 80 years of age.
- Has been taking allopurinol as the sole urate lowering therapy for hyperuricemia for at least 6 weeks at a dose between 200 mg and 600 mg per day without an adequate response.
- Has a sUA level ≥ 6 mg/dL at screening.
- Meets criteria for the diagnosis of gout as per the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout.
- Willing and able to give informed consent and adhere to visit/protocol schedules (informed consent must be given before the first study procedure is performed).
- Subjects entering the optional Extension Period must have completed 28 days of dosing in the Double-Blind Treatment Period and the Day 42 Visit in the Follow-up Period within 4 months and must not have experienced any serious adverse events considered possibly related to study drug.
- Subjects entering the optional Open-Label Extension Period must continue to be compliant with the protocol through Week 44 of the Double-Blind Extension Period and must not have experienced any serious adverse events considered possibly related to study drug.
Who cannot join
- Consumes more than 14 drinks of alcohol per week (e.g., 1 drink = 5 oz [150 ml] of wine, 12 oz [360 ml] of beer, or 1.5 oz [45 ml] of hard liquor).
- History or suspicion of drug abuse.
- History of documented or suspected kidney stones.
- Has rheumatoid arthritis or other autoimmune disease requiring treatment.
- Documented or suspicion of HIV infection.
- Positive serology to HCV antibodies (Abs), and/or hepatitis B surface antigen (HBsAg).
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- History of malignancy within 5 years prior to the first dose of study medication, other than non-melanomatous skin cancer or cervical dysplasia.
- History of cardiac abnormalities, including abnormal and clinically relevant ECG changes
- Any condition predisposing to QT prolongation including pathological Q-wave (defined as Q-wave >40 msec or depth > 0.4-0.5 mV).
- Any use of concomitant medications that prolong the QT/QTc interval within the 14 days prior to Baseline (Day 1).
- QT interval corrected for heart rate according to Fridericia (QTcF) > 450 msec at Screening or pre-dose at Baseline (Day 1).
- Uncontrolled hypertension (above 150/95).
- Inadequate renal function [serum creatinine >1.5 mg/dL or creatinine clearance < 60 mL/min (by Cockroft-Gault formula)].
- Hemoglobin < 10 g/dL (males) or < 9 g/dL (females).
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN).
- Gamma glutamyl transferase (GGT) > 3 x ULN.
- Active peptic ulcer disease requiring treatment.
- History of xanthinuria, active liver disease, or hepatic dysfunction.
- Requires therapy with any other urate-lowering medication, other than the study medications.
- Requires long-term use of salicylates; diuretics; losartan; azathioprine; mercaptopurine; theophylline; intravenous colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole; or trimethoprim.
- Taking medications known as enzyme inducers (see section 3.7 for listing).
- Reports receiving a strong or moderate inhibitor of CYP3A4 or a P-gp inhibitor within 1 month prior to study drug dosing, due to potential interactions with colchicine.
- Acute gout flare (exclusive of chronic synovitis/ arthritis) during the Screening-Period that has not resolved one week prior to the Baseline Visit (Day 0).
- Pregnant or breast feeding.
- Has received an investigational medication within 4 weeks prior to the screening visit for this study.
- Previously participated in a clinical study involving RDEA806 or RDEA594.
- Known hypersensitivity or allergy to RDEA594, allopurinol or colchicine or any components in their formulations.
- Body mass index (BMI) >48 kg/m2.
- Taking greater than 1000 mg/day of Vitamin C.
- Any other medical or psychological condition, which in the opinion of the Investigator and/or Medical Monitor, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements, or to complete the study.
- Inadequate renal function after completing the Double-Blind Treatment period prior to entering Double-Blind Extension Period.
- Requiring treatment with prohibited medications noted in exclusion criteria numbers 20-23 after completing the Double-Blind Treatment Period prior to entering the Extension Period.
- Clinically relevant medical event as determined by the investigator in consultation with medical monitor prior to entering the Extension Period.
Trial locations and contacts
44 sites in 6 countries.
44 sites in 6 countries
United States25 sites
Study site
Boca Raton, Florida, 33432
Study site
Chesapeake, Virginia, 23320
Study site
Cincinnati, Ohio, 45242
Study site
Cleveland, Ohio, 44122
Study site
Dallas, Texas, 75231
Study site
DeLand, Florida, 32720
Study site
Durham, South Carolina, 27710
Study site
Fort Lauderdale, Florida, 33334
Study site
Germantown, Tennessee, 38138
Study site
Harrisburg, North Carolina, 28075
Study site
Jackson, Tennessee, 38305
Study site
Jupiter, Florida, 33458
Study site
La Jolla, California, 92037
Study site
Las Vegas, Nevada, 89183
Study site
Lexington, Kentucky, 40504
Study site
Los Angeles, California, 90017
Study site
Mayfield Village, Ohio, 44143
Study site
Meridan, Idaho, 83642
Study site
Phoenix, Arizona, 85050
Study site
Reno, Nevada, 89502
Study site
Rock Hill, South Carolina, 29732
Study site
San Antonio, Texas, 78221
Study site
Stanford, California, 94305
Study site
West Jordan, Utah, 84088
Study site
Wheaton, Maryland, 20902
Canada6 sites
Study site
Coquitlam, British Columbia, V3K 3P4
Study site
Kelowna, British Columbia, V1Y8E7
Study site
Mirabel, Quebec, J7J 2K8
Study site
St. John's, Newfoundland and Labrador, A1A 3R5
Study site
Thornhill, Ontario, L4J 6W6
Study site
Toronto, Ontario, M9W 4L6
Poland6 sites
Study site
Bydgoszcz, 85-168
Study site
Elblag, 82-300
Study site
Lublin, 20-607
Study site
Poznan, 60-773
Study site
Radom, 26-610
Study site
Torun, 87-100
Ukraine5 sites
Study site
Donetsk, 83045
Study site
Kharkiv, 61176
Study site
Kyiv, 01610
Study site
Kyiv, 02125
Study site
Vinnytsia, 21081
About this study
Official title: Randomized, Double-Blind, Multicenter, Placebo-Controlled, Combination Study to Evaluate the Safety, Efficacy and Potential Pharmacokinetic Interaction of RDEA594 and Allopurinol in Gout Patients With an Inadequate Hypouricemic Response With Standard Doses of Allopurinol
To compare the proportion of subjects whose serum urate (sUA) levels are < 6.0 mg/dL following 4 weeks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response with standard doses of allopurinol.
- Conditions
- Gout
- Being tested
- RDEA594, Placebo, Allopurinol
- Medical subject headings
- Gout
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RDEA594Drug
Uricosuric agent for the treatment of gout.
PlaceboDrug
Matching Placebo
AllopurinolDrug
Allopurinol
| Study group | Role | What they receive |
|---|---|---|
| RDEA594 200 mg qd | Experimental | RDEA594 200 mg qd plus allopurinol qd Receives: Drug: RDEA594; Drug: Allopurinol |
| RDEA594 200 mg, 400 mg qd | Experimental | RDEA594 200 mg then 400 mg qd plus allopurinol qd.
Patients on lesinurad 400 mg had their dose changed to lesinurad 200 mg after protocol amendment 16 dated 07 October 2015. Receives: Drug: RDEA594; Drug: Allopurinol |
| Matching Placebo | Placebo comparator | RDEA594 matching placebo qd plus allopurinol qd, then allopurinol qd alone in open label period.
Patients on allopurinol qd alone were discontinued after protocol amendment 16 dated 07 October 2015. Receives: Drug: Placebo; Drug: Allopurinol |
| RDEA594 600 mg qd | Experimental | RDEA594 200 mg then 400 mg then 600 mg plus allopurinol qd
Patients on lesinurad 600 mg had their dose changed to lesinurad 200 mg after protocol amendment 16 dated 07 October 2015. Receives: Drug: RDEA594; Drug: Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the percent reduction from baseline in serum urate levels following 4 wks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response.
Measured: 28 days
Secondary outcomes (7)
To evaluate the proportion of subjects whose sUA levels are < 6.0 mg/dL, < 5.0 mg/dL and < 4.0 mg/dL at each study visit by treatment group in all subjects and in subjects who have an sUA ≥6 mg/dL at the baseline visit.
Measured: 28 days and through extension
To evaluate the absolute and percent reduction from baseline in sUA levels at each visit.
Measured: 28 days and through extension
To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28.
Measured: 28 days and through extension
To evaluate the incidence of gout flares.
Measured: 28 days and through extension
To evaluate the safety and tolerability of RDEA594 in combination with allopurinol in subjects with gout.
Measured: 28 days and through extension
To compare the multiple-dose pharmacokinetics (PK) of allopurinol and oxypurinol in the absence versus presence of RDEA594 co-administration.
Measured: 28 days
To evaluate the proportion of subjects whose sUA level decreases to or is maintained at <6.0 mg/dL and <5.0 mg/dL in the Double-Blind and Open-Label Extension Period.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionJan 2011
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GoutStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 227 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ardea Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nihar Bhakta, MD, Study director, Ardea Biosciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01001338
- Sponsor's protocol ID
- RDEA594-203
- Acronym
- RDEA594-203
- Status last verified
- Jan 2017
- First submitted
- 22 Oct 2009
- Last updated
- 24 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Perez-Ruiz F, Sundy JS, Miner JN, Cravets M, Storgard C; RDEA594-203 Study Group. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis. 2016 Jun;75(6):1074-80. doi: 10.1136/annrheumdis-2015-207919. Epub 2016 Jan 7.
PubMed 26742777
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Blind, Multicenter, Placebo-Controlled, Combination Study to Evaluate the Safety, Efficacy and Potential Pharmacokinetic Interaction of RDEA594 and Allopurinol in Gout Patients With an Inadequate Hypouricemic Response With Standard Doses of Allopurinol
- ClinicalTrials.gov ID
- NCT01001338
- Acronym / sponsor ID
- RDEA594-203 / RDEA594-203
- Conditions
- Gout
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 227 participants (actual)
- Lead sponsor
- Ardea Biosciences, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 26 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare the proportion of subjects whose serum urate (sUA) levels are < 6.0 mg/dL following 4 weeks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response with standard doses of allopurinol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| RDEA594 200 mg qd | Experimental | Drug: RDEA594, Drug: AllopurinolRDEA594 200 mg qd plus allopurinol qd |
| RDEA594 200 mg, 400 mg qd | Experimental | Drug: RDEA594, Drug: AllopurinolRDEA594 200 mg then 400 mg qd plus allopurinol qd. Patients on lesinurad 400 mg had their dose changed to lesinurad 200 mg after protocol amendment 16 dated 07 October 2015. |
| Matching Placebo | Placebo comparator | Drug: Placebo, Drug: AllopurinolRDEA594 matching placebo qd plus allopurinol qd, then allopurinol qd alone in open label period. Patients on allopurinol qd alone were discontinued after protocol amendment 16 dated 07 October 2015. |
| RDEA594 600 mg qd | Experimental | Drug: RDEA594, Drug: AllopurinolRDEA594 200 mg then 400 mg then 600 mg plus allopurinol qd Patients on lesinurad 600 mg had their dose changed to lesinurad 200 mg after protocol amendment 16 dated 07 October 2015. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or a post-menopausal or surgically sterile female.
- 18 - 80 years of age.
- Has been taking allopurinol as the sole urate lowering therapy for hyperuricemia for at least 6 weeks at a dose between 200 mg and 600 mg per day without an adequate response.
- Has a sUA level ≥ 6 mg/dL at screening.
- Meets criteria for the diagnosis of gout as per the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout.
Key exclusion criteria (33 listed)
- Consumes more than 14 drinks of alcohol per week (e.g., 1 drink = 5 oz [150 ml] of wine, 12 oz [360 ml] of beer, or 1.5 oz [45 ml] of hard liquor).
- History or suspicion of drug abuse.
- History of documented or suspected kidney stones.
- Has rheumatoid arthritis or other autoimmune disease requiring treatment.
- Documented or suspicion of HIV infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RDEA594Uricosuric agent for the treatment of gout. | Drug | RDEA594 200 mg qd, RDEA594 200 mg, 400 mg qd, RDEA594 600 mg qd |
| PlaceboMatching Placebo | Drug | Matching Placebo |
| AllopurinolAllopurinol | Drug | Matching Placebo, RDEA594 200 mg qd, RDEA594 200 mg, 400 mg qd, RDEA594 600 mg qd |
Primary outcome
To compare the percent reduction from baseline in serum urate levels following 4 wks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response.
Time frame: 28 days
7 secondary outcomes
To evaluate the proportion of subjects whose sUA levels are < 6.0 mg/dL, < 5.0 mg/dL and < 4.0 mg/dL at each study visit by treatment group in all subjects and in subjects who have an sUA ≥6 mg/dL at the baseline visit.
Time frame: 28 days and through extension
To evaluate the absolute and percent reduction from baseline in sUA levels at each visit.
Time frame: 28 days and through extension
To evaluate the percentage change in 24-hour urine urate level (excretion) from baseline to Day 28.
Time frame: 28 days and through extension
To evaluate the incidence of gout flares.
Time frame: 28 days and through extension
To evaluate the safety and tolerability of RDEA594 in combination with allopurinol in subjects with gout.
Time frame: 28 days and through extension
To compare the multiple-dose pharmacokinetics (PK) of allopurinol and oxypurinol in the absence versus presence of RDEA594 co-administration.
Time frame: 28 days
To evaluate the proportion of subjects whose sUA level decreases to or is maintained at <6.0 mg/dL and <5.0 mg/dL in the Double-Blind and Open-Label Extension Period.
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2017.
- Derived from this study: PubMed 26742777Perez-Ruiz F, Sundy JS, Miner JN, Cravets M, Storgard C; RDEA594-203 Study Group. Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol. Ann Rheum Dis. 2016 Jun;75(6):1074-80. doi: 10.1136/annrheumdis-2015-207919. Epub 2016 Jan 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nihar Bhakta, MD study director
Ardea Biosciences, Inc.
44 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RDEA594 and Allopurinol in people with Gout, run by Ardea Biosciences, Inc. at 44 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Canada, Poland, Ukraine, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the percent reduction from baseline in serum urate levels following 4 wks of continuous treatment of RDEA594 in combination with allopurinol to allopurinol alone in subjects with documented inadequate hypouricemic response. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01001338, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2017.