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A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients

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ClinicalTrials.gov Identifier: NCT02317861
Recruitment Status : Completed
First Posted : December 17, 2014
Last Update Posted : June 12, 2015
Sponsor:
Collaborator:
Ardea Biosciences, Inc.
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The purpose of this study is to explore the pharmacodynamics (PD), pharmacokinetics (PK), safety, and tolerability of multiple doses of RDEA3170 administered in combination with febuxostat compared to RDEA3170 administered alone and febuxostat administered alone in Japanese adult male subjects with gout or asymptomatic hyperuricemia.

Condition or disease Intervention/treatment Phase
Gout and Asymptomatic Hyperuricemia Drug: RDEA3170 Drug: Febuxostat Drug: Benzbromarone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase 2a, Randomized, Open-Label, Single-Site Study to Evaluate the Pharmacodynamic Effects and Safety of RDEA3170 Administered in Combination With Febuxostat Compared to RDEA3170 Administered Alone and Febuxostat Administered Alone, Respectively in Japanese Adult Male Subjects With Gout or Asymptomatic Hyperuricemia
Study Start Date : December 2014
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Gout
MedlinePlus related topics: Gout
Drug Information available for: Febuxostat

Arm Intervention/treatment
Experimental: Cohort 1
The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 10mg, RDEA3170 2.5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order.
Drug: RDEA3170
Oral Treatment

Drug: Febuxostat
Oral Treatment

Experimental: Cohort 2
The half of patients randomized to this cohort will be dosed in the order of Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 10mg, RDEA3170 5 mg + Febuxostat 20mg, and Febuxostat 20mg. The other half will be dosed in the reverse order.
Drug: RDEA3170
Oral Treatment

Drug: Febuxostat
Oral Treatment

Experimental: Cohort 3
The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 20mg, RDEA3170 5 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order.
Drug: RDEA3170
Oral Treatment

Drug: Febuxostat
Oral Treatment

Experimental: Cohort 4
The half of patients randomized to this cohort will be dosed in the order of Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 20mg, RDEA3170 10 mg + Febuxostat 40mg, and Febuxostat 40mg. The other half will be dosed in the reverse order.
Drug: RDEA3170
Oral Treatment

Drug: Febuxostat
Oral Treatment

Experimental: Cohort 5
RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg
Drug: RDEA3170
Oral Treatment

Experimental: Cohort 6
The half of patients randomized to this cohort will be dosed in the order of Benzbromarone 50 mg, Febuxostat 10mg+RDEA3170 2.5 mg, then Febuxostat 20mg+RDEA3170 5 mg. The other half will be dosed in the order of Febuxostat 10mg+RDEA3170 2.5 mg, Febuxostat 20mg+RDEA3170 5 mg, then Benzbromarone 50mg.
Drug: RDEA3170
Oral Treatment

Drug: Febuxostat
Oral Treatment

Drug: Benzbromarone
Oral Treatment




Primary Outcome Measures :
  1. Change in Serum uric acid level [ Time Frame: baseline and day 7 on each treatment ]
    % change per treatment will be compared.

  2. Change in Urinary excretion of uric acid [ Time Frame: baseline and day 7 on each treatment ]
    Timed urinary uric acid excretion per treatment will be compared

  3. Renal clearance of uric acid [ Time Frame: baseline and day 7 on each treatment ]
    Renal clearance of uric acid will be calculated.

  4. Fractional excretion of uric acid [ Time Frame: baseline and day 7 on each treatment ]
    Fractional excretion and renal clearance of uric acid will be calculated.


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment ]
    To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.

  2. Time to reach maximum concentration (tmax) [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment ]
    To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.

  3. Area under the concentration-time curve (AUC) [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment ]
    To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.

  4. Half life (t1/2) [ Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post‐dose on each treatment ]
    To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.

  5. Incidence of adverse events [ Time Frame: Day 1 and Day 7 on each treatment ]
    To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170

  6. Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters [ Time Frame: Day 1 and Day 8 on each treatment ]
    To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170

  7. Changes in vital signs and physical examination findings [ Time Frame: Day 1 and Day 8 on each treatment ]
    To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170

  8. Incidence of adverse events [ Time Frame: Day 42 of the study as follow up ]
    To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170

  9. Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters [ Time Frame: Day 42 of the study as follow up ]
    To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170

  10. Changes in vital signs and physical examination findings [ Time Frame: Day 42 of the study as follow up ]
    To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170


Other Outcome Measures:
  1. Change in Urinary pH [ Time Frame: baseline and day 7 on each treatment ]
    To evaluate the relationship between the doses of uralyt and urinary pH under the administration of RDEA3170.

  2. Deoxyribonucleic acid polymorphism [ Time Frame: Day 1 of the study as randomization ]
    To collect and store deoxyribonucleic acid (DNA) for future exploratory research.

  3. Change in Serum uric acid level [ Time Frame: Baseline and day 7 on each treatment for cohort 6 ]
    % change per treatment will be compared.

  4. Change in Urinary excretion of uric acid [ Time Frame: Baseline and day 7 on each treatment for cohort 6 ]
    Timed urinary uric acid excretion per treatment will be compared.

  5. Renal clearance of uric acid [ Time Frame: Baseline and day 7 on each treatment for cohort 6 ]
    Renal clearance of uric acid will be calculated.

  6. Fractional excretion of uric acid [ Time Frame: Baseline and day 7 on each treatment for cohort 6 ]
    Fractional excretion and renal clearance of uric acid will be calculated.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Screening serum uric acid level ≥ 8 mg/dL;
  • Body weight ≥ 50 kg and a body mass index (BMI) ≥ 18 and ≤ 40 kg/m2;
  • Free of any clinically significant disease or medical condition, per the Investigator's judgment.

Exclusion Criteria:

  • History or suspicion of kidney stones;
  • Diagnosis of benign prostatic hypertrophy (BPH) or neurogenic bladder or evidence of BPH/neurogenic bladder such as thin urinary stream or difficulty in urination;
  • An estimated creatinine clearance < 60 mL/min calculated by the Cockcroft-Gault formula;
  • QTcF interval (QT interval corrected for heart rate using Fridericia's formula) > 450 msec at Screening;
  • Receiving strong or moderate Cytochrome P450 (CYP) 3A inhibitors or p-glycoprotein inhibitors, or digoxin

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02317861


Locations
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Japan
Research Site
Fukuoka-shi, Japan
Sponsors and Collaborators
AstraZeneca
Ardea Biosciences, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02317861     History of Changes
Other Study ID Numbers: D5491L00001
RDEA3170-205 ( Other Identifier: Ardea Biosciences, Inc. )
First Posted: December 17, 2014    Key Record Dates
Last Update Posted: June 12, 2015
Last Verified: June 2015

Additional relevant MeSH terms:
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Febuxostat
Gout
Hyperuricemia
Arthritis
Joint Diseases
Musculoskeletal Diseases
Crystal Arthropathies
Rheumatic Diseases
Purine-Pyrimidine Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Pathologic Processes
Benzbromarone
Gout Suppressants
Antirheumatic Agents
Uricosuric Agents
Renal Agents