NCT02317861

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
110

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Dec 2014

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2014

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

December 9, 2014

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 17, 2014

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2015

Completed
Last Updated

June 12, 2015

Status Verified

June 1, 2015

Enrollment Period

6 months

First QC Date

December 9, 2014

Last Update Submit

June 11, 2015

Conditions

Gout and Asymptomatic Hyperuricemia

Outcome Measures

Primary Outcomes (4)

  • Change in Serum uric acid level

    % change per treatment will be compared.

    baseline and day 7 on each treatment

  • Change in Urinary excretion of uric acid

    Timed urinary uric acid excretion per treatment will be compared

    baseline and day 7 on each treatment

  • Renal clearance of uric acid

    Renal clearance of uric acid will be calculated.

    baseline and day 7 on each treatment

  • Fractional excretion of uric acid

    Fractional excretion and renal clearance of uric acid will be calculated.

    baseline and day 7 on each treatment

Secondary Outcomes (10)

  • Maximum plasma concentration (Cmax)

    0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment

  • Time to reach maximum concentration (tmax)

    0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment

  • Area under the concentration-time curve (AUC)

    0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment

  • Half life (t1/2)

    0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment

  • Incidence of adverse events

    Day 1 and Day 7 on each treatment

  • +5 more secondary outcomes

Other Outcomes (6)

  • Change in Urinary pH

    baseline and day 7 on each treatment

  • Deoxyribonucleic acid polymorphism

    Day 1 of the study as randomization

  • Change in Serum uric acid level

    Baseline and day 7 on each treatment for cohort 6

  • +3 more other outcomes

Study Arms (6)

Cohort 1

EXPERIMENTAL

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: RDEA3170Drug: Febuxostat

Cohort 2

EXPERIMENTAL

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: RDEA3170Drug: Febuxostat

Cohort 3

EXPERIMENTAL

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: RDEA3170Drug: Febuxostat

Cohort 4

EXPERIMENTAL

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: RDEA3170Drug: Febuxostat

Cohort 5

EXPERIMENTAL

RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg

Drug: RDEA3170

Cohort 6

EXPERIMENTAL

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: RDEA3170Drug: FebuxostatDrug: Benzbromarone

Interventions

RDEA3170DRUG

Oral Treatment

Cohort 1Cohort 2Cohort 3Cohort 4Cohort 5Cohort 6
FebuxostatDRUG

Oral Treatment

Cohort 1Cohort 2Cohort 3Cohort 4Cohort 6
BenzbromaroneDRUG

Oral Treatment

Cohort 6

Eligibility Criteria

Age20 Years - 70 Years
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Research Site

Fukuoka, Japan

Location

Related Publications (2)

  • Rekic D, Johansson S, Leander J. Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight. Clin Pharmacokinet. 2021 Mar;60(3):319-328. doi: 10.1007/s40262-020-00943-6. Epub 2020 Sep 19.

    PMID: 32951150DERIVED

  • Shiramoto M, Liu S, Shen Z, Yan X, Yamamoto A, Gillen M, Ito Y, Hall J. Verinurad combined with febuxostat in Japanese adults with gout or asymptomatic hyperuricaemia: a phase 2a, open-label study. Rheumatology (Oxford). 2018 Sep 1;57(9):1602-1610. doi: 10.1093/rheumatology/key100.

    PMID: 29868853DERIVED

MeSH Terms

Conditions

Gout

Interventions

verinuradFebuxostatBenzbromarone

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesCrystal ArthropathiesRheumatic DiseasesPurine-Pyrimidine Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsBenzofuransHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 9, 2014

First Posted

December 17, 2014

Study Start

December 1, 2014

Primary Completion

June 1, 2015

Study Completion

June 1, 2015

Last Updated

June 12, 2015

Record last verified: 2015-06

Locations

JP(1)