Gout and Asymptomatic HyperuricemiaPhase 1/2NCT02317861
A PD/Safety Study of RDEA3170 in Combination With Febuxostat for Treating Gout or Asymptomatic Hyperuricemia Patients
A Phase 1/2 study testing RDEA3170, Febuxostat and Benzbromarone in people with Gout and Asymptomatic Hyperuricemia, run by AstraZeneca at 1 site in Japan.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 70 years, men only
- Conditions the study is for
- Gout and Asymptomatic Hyperuricemia
- What is being tested?
- RDEA3170, Febuxostat and Benzbromarone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteJapan
- Study dates
- Dec 2014to Jun 2015
- Phase
- Phase 1/2
- 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 20 to 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Gout and Asymptomatic Hyperuricemia
- Being tested
- RDEA3170, Febuxostat, Benzbromarone
- Medical subject headings
- Gout
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RDEA3170Drug
Oral Treatment
FebuxostatDrug
Oral Treatment
BenzbromaroneDrug
Oral Treatment
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: RDEA3170; Drug: 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. Receives: Drug: RDEA3170; Drug: 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. Receives: Drug: RDEA3170; Drug: 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. Receives: Drug: RDEA3170; Drug: Febuxostat |
| Cohort 5 | Experimental | RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg Receives: 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. Receives: Drug: RDEA3170; Drug: Febuxostat; Drug: Benzbromarone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Serum uric acid level
% change per treatment will be compared.
Measured: baseline and day 7 on each treatment
Change in Urinary excretion of uric acid
Timed urinary uric acid excretion per treatment will be compared
Measured: baseline and day 7 on each treatment
Renal clearance of uric acid
Renal clearance of uric acid will be calculated.
Measured: baseline and day 7 on each treatment
Fractional excretion of uric acid
Fractional excretion and renal clearance of uric acid will be calculated.
Measured: baseline and day 7 on each treatment
Secondary outcomes (10)
Maximum plasma concentration (Cmax)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Measured: 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)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Measured: 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)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Half life (t1/2)
To assess multiple-dose PK of RDEA3170 and febuxostat alone or in combination treatment.
Measured: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 , 24 hours post-dose on each treatment
Incidence of adverse events
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Measured: Day 1 and Day 7 on each treatment
Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Measured: Day 1 and Day 8 on each treatment
Changes in vital signs and physical examination findings
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Measured: Day 1 and Day 8 on each treatment
Incidence of adverse events
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Measured: Day 42 of the study as follow up
Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Measured: Day 42 of the study as follow up
Changes in vital signs and physical examination findings
To evaluate the safety and tolerability of febuxostat alone, RDEA3170 alone and RDEA3170 administered in combination of febuxostat and febuxostat in combination of RDEA3170
Measured: Day 42 of the study as follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gout and Asymptomatic HyperuricemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ardea Biosciences, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02317861
- Sponsor's protocol ID
- D5491L00001
- Other IDs
- RDEA3170-205
- Status last verified
- Jun 2015
- First submitted
- 9 Dec 2014
- Last updated
- 12 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 32951150Shiramoto 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.
PubMed 29868853
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02317861
- Acronym / sponsor ID
- D5491L00001
- Conditions
- Gout and Asymptomatic Hyperuricemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Ardea Biosciences, Inc.
- Study start
- Dec 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 17 Dec 2014 (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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: RDEA3170, Drug: FebuxostatThe 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. |
| Cohort 2 | Experimental | Drug: RDEA3170, Drug: FebuxostatThe 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. |
| Cohort 3 | Experimental | Drug: RDEA3170, Drug: FebuxostatThe 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. |
| Cohort 4 | Experimental | Drug: RDEA3170, Drug: FebuxostatThe 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. |
| Cohort 5 | Experimental | Drug: RDEA3170RDEA3170 2.5mg, RDEA3170 5mg, RDEA3170 10mg, RDEA3170 15mg |
| Cohort 6 | Experimental | Drug: RDEA3170, Drug: Febuxostat, Drug: BenzbromaroneThe 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. |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
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 |
|---|---|---|
| RDEA3170Oral Treatment | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
| FebuxostatOral Treatment | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 6 |
| BenzbromaroneOral Treatment | Drug | Cohort 6 |
Primary outcome
Change in Serum uric acid level
Time frame: baseline and day 7 on each treatment
% change per treatment will be compared.
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
Renal clearance of uric acid
Time frame: baseline and day 7 on each treatment
Renal clearance of uric acid will be calculated.
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.
10 secondary outcomes
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
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
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
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
Incidence of adverse events
Time frame: Day 1 and Day 7 on each treatment
Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
Time frame: Day 1 and Day 8 on each treatment
Changes in vital signs and physical examination findings
Time frame: Day 1 and Day 8 on each treatment
Incidence of adverse events
Time frame: Day 42 of the study as follow up
Changes in hematology, serum chemistry, coagulation, electrocardiogram and urinalysis parameters
Time frame: Day 42 of the study as follow up
Changes in vital signs and physical examination findings
Time frame: Day 42 of the study as follow up
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 12 Jun 2015.
- Derived from this study: PubMed 32951150Rekic 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.
- Derived from this study: PubMed 29868853Shiramoto 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RDEA3170, Febuxostat and Benzbromarone in people with Gout and Asymptomatic Hyperuricemia, run by AstraZeneca at 1 site in Japan.
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 3 inclusion and 5 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 12 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Change in Serum uric acid level (time frame: baseline and day 7 on each treatment). The study lists 4 primary outcomes in all. 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 NCT02317861, which also lists 2 linked publications.
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 12 Jun 2015.