Allopurinol Combination Study

NCT ID: NCT01001338

Last Updated: 2017-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

227 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2016-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Gout

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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RDEA594 200 mg qd

RDEA594 200 mg qd plus allopurinol qd

Group Type EXPERIMENTAL

RDEA594

Intervention Type DRUG

Uricosuric agent for the treatment of gout.

Allopurinol

Intervention Type DRUG

Allopurinol

RDEA594 200 mg, 400 mg qd

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.

Group Type EXPERIMENTAL

RDEA594

Intervention Type DRUG

Uricosuric agent for the treatment of gout.

Allopurinol

Intervention Type DRUG

Allopurinol

Matching Placebo

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching Placebo

Allopurinol

Intervention Type DRUG

Allopurinol

RDEA594 600 mg qd

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.

Group Type EXPERIMENTAL

RDEA594

Intervention Type DRUG

Uricosuric agent for the treatment of gout.

Allopurinol

Intervention Type DRUG

Allopurinol

Interventions

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RDEA594

Uricosuric agent for the treatment of gout.

Intervention Type DRUG

Placebo

Matching Placebo

Intervention Type DRUG

Allopurinol

Allopurinol

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or a post-menopausal or surgically sterile female.
2. 18 - 80 years of age.
3. 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.
4. Has a sUA level ≥ 6 mg/dL at screening.
5. Meets criteria for the diagnosis of gout as per the American Rheumatism Association (ARA) Criteria for the Classification of Acute Arthritis of Primary Gout.
6. 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).
7. 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.
8. 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.

Exclusion Criteria

1. 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).
2. History or suspicion of drug abuse.
3. History of documented or suspected kidney stones.
4. Has rheumatoid arthritis or other autoimmune disease requiring treatment.
5. Documented or suspicion of HIV infection.
6. Positive serology to HCV antibodies (Abs), and/or hepatitis B surface antigen (HBsAg).
7. History of malignancy within 5 years prior to the first dose of study medication, other than non-melanomatous skin cancer or cervical dysplasia.
8. History of cardiac abnormalities, including abnormal and clinically relevant ECG changes
9. Any condition predisposing to QT prolongation including pathological Q-wave (defined as Q-wave \>40 msec or depth \> 0.4-0.5 mV).
10. Any use of concomitant medications that prolong the QT/QTc interval within the 14 days prior to Baseline (Day 1).
11. QT interval corrected for heart rate according to Fridericia (QTcF) \> 450 msec at Screening or pre-dose at Baseline (Day 1).
12. Uncontrolled hypertension (above 150/95).
13. Inadequate renal function \[serum creatinine \>1.5 mg/dL or creatinine clearance \< 60 mL/min (by Cockroft-Gault formula)\].
14. Hemoglobin \< 10 g/dL (males) or \< 9 g/dL (females).
15. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 x upper limit of normal (ULN).
16. Gamma glutamyl transferase (GGT) \> 3 x ULN.
17. Active peptic ulcer disease requiring treatment.
18. History of xanthinuria, active liver disease, or hepatic dysfunction.
19. Requires therapy with any other urate-lowering medication, other than the study medications.
20. Requires long-term use of salicylates; diuretics; losartan; azathioprine; mercaptopurine; theophylline; intravenous colchicine; cyclosporine; cyclophosphamide; pyrazinamide; sulfamethoxazole; or trimethoprim.
21. Taking medications known as enzyme inducers (see section 3.7 for listing).
22. 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.
23. 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).
24. Pregnant or breast feeding.
25. Has received an investigational medication within 4 weeks prior to the screening visit for this study.
26. Previously participated in a clinical study involving RDEA806 or RDEA594.
27. Known hypersensitivity or allergy to RDEA594, allopurinol or colchicine or any components in their formulations.
28. Body mass index (BMI) \>48 kg/m2.
29. Taking greater than 1000 mg/day of Vitamin C.
30. 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.
31. Inadequate renal function after completing the Double-Blind Treatment period prior to entering Double-Blind Extension Period.
33. Clinically relevant medical event as determined by the investigator in consultation with medical monitor prior to entering the Extension Period.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ardea Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nihar Bhakta, MD

Role: STUDY_DIRECTOR

Ardea Biosciences, Inc.

Locations

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Phoenix, Arizona, United States

Site Status

La Jolla, California, United States

Site Status

Los Angeles, California, United States

Site Status

Stanford, California, United States

Site Status

Boca Raton, Florida, United States

Site Status

DeLand, Florida, United States

Site Status

Fort Lauderdale, Florida, United States

Site Status

Jupiter, Florida, United States

Site Status

Meridan, Idaho, United States

Site Status

Lexington, Kentucky, United States

Site Status

Wheaton, Maryland, United States

Site Status

Las Vegas, Nevada, United States

Site Status

Reno, Nevada, United States

Site Status

Harrisburg, North Carolina, United States

Site Status

Cincinnati, Ohio, United States

Site Status

Cleveland, Ohio, United States

Site Status

Mayfield Village, Ohio, United States

Site Status

Durham, South Carolina, United States

Site Status

Rock Hill, South Carolina, United States

Site Status

Germantown, Tennessee, United States

Site Status

Jackson, Tennessee, United States

Site Status

Dallas, Texas, United States

Site Status

San Antonio, Texas, United States

Site Status

West Jordan, Utah, United States

Site Status

Chesapeake, Virginia, United States

Site Status

Coquitlam, British Columbia, Canada

Site Status

Kelowna, British Columbia, Canada

Site Status

St. John's, Newfoundland and Labrador, Canada

Site Status

Thornhill, Ontario, Canada

Site Status

Toronto, Ontario, Canada

Site Status

Mirabel, Quebec, Canada

Site Status

Bydgoszcz, , Poland

Site Status

Elblag, , Poland

Site Status

Lublin, , Poland

Site Status

Poznan, , Poland

Site Status

Radom, , Poland

Site Status

Torun, , Poland

Site Status

Bilbao, , Spain

Site Status

Donetsk, , Ukraine

Site Status

Kharkiv, , Ukraine

Site Status

Kyiv, , Ukraine

Site Status

Kyiv, , Ukraine

Site Status

Vinnytsia, , Ukraine

Site Status

Blackpool, Lancashire, United Kingdom

Site Status

Countries

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United States Canada Poland Spain Ukraine United Kingdom

References

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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.

Reference Type DERIVED
PMID: 26742777 (View on PubMed)

Other Identifiers

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RDEA594-203

Identifier Type: -

Identifier Source: org_study_id

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