Allopurinol Combination Study - RDEA594-203

Study identifier:RDEA594-203

ClinicalTrials.gov identifier:NCT01001338

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Gout

Phase

Phase 2

Healthy volunteers

Study drug

RDEA594, Placebo, Allopurinol

Sex

All

Actual Enrollment

227

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 01 Oct 2009

Primary Completion Date: 01 Jan 2011

Study Completion Date: 01 Aug 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Factorial Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2017 by Ardea Biosciences, Inc.

Collaborators

Inclusion and exclusion criteria

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.
32. 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.
33. Clinically relevant medical event as determined by the investigator in consultation with medical monitor prior to entering the Extension Period.

No locations available

Arms	Assigned Interventions
Experimental: RDEA594 200 mg qd RDEA594 200 mg qd plus allopurinol qd	Drug: RDEA594 Uricosuric agent for the treatment of gout. Drug: Allopurinol Allopurinol
Experimental: 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.	Drug: RDEA594 Uricosuric agent for the treatment of gout. Drug: Allopurinol Allopurinol
Placebo Comparator: 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.	Drug: Placebo Matching Placebo Drug: Allopurinol Allopurinol
Experimental: 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.	Drug: RDEA594 Uricosuric agent for the treatment of gout. Drug: Allopurinol Allopurinol

Documents available

Trial Results Summaries
Available here

Contacts

Contact

J Sosa

858.652.6572

Investigators

Principal Investigator

Nihar Bhakta

Ardea Biosciences, Inc.