HyperuricosuriaPhase 2NCT01077284

Febuxostat Versus Allopurinol or Placebo in Patients With Hyperuricosuria and Calcium Oxalate Stones

A Phase 2 study testing Febuxostat and Allopurinol in people with Hyperuricosuria and Kidney Stones, run by Takeda at 28 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine the efficacy of febuxostat, once daily (QD), compared to allopurinol or placebo in patients with excessive amounts of uric acid in their urine and who have recently had kidney stones. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hyperuricosuria, Kidney Stones
What is being tested?: Febuxostat and Allopurinol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 99 participants
Where: 28 sitesUnited States
Study dates: Feb 2010to Nov 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Has hyperuricosuria, defined as a daily urine uric acid excretion greater than 700 mg as measured by 24-hour urine collection prior to randomization.
Has at least one calcium oxalate stone greater than or equal to 3 mm in its longest in-plane diameter, identified by Multiple Detector Computated Tomography prior to randomization.
Has a recent (within the previous 5 years) history of renal stones prior to screening.

Who cannot join

Has gout, secondary hyperuricemia or has experienced a gout flare.
Has a history of xanthinuria.
Has received allopurinol or probenecid within 2 years prior to randomization.
Has received febuxostat.
Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0 times the upper limit of normal at the Screening Visit.
Has an abnormal serum calcium level at the Screening Visit.

Show all 26Show fewer

Has a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol according to the judgment of the Investigator.
Has a history of drug abuse or a history of alcohol abuse within 5 years prior to the Screening Visit.
Participant's measured creatinine clearance is less than 30 mL/min at the Screening Visit.
Has hypercalciuria at Screening, while on a regular unrestricted diet, defined as urinary excretion of:
greater than 250 mg of calcium/24-hour for females of body weight less than 62.5 kg; OR
greater than 300 mg calcium/24-hour for males of body weight less than 75 kg; OR
greater than 4 mg calcium/kg/24-hour for males of body weight greater than or equal 75 kg and females of body weight greater than or equal 62.5 kg.
EXCLUDED MEDICATIONS:
Febuxostat, allopurinol, probenecid.
Salicylates (chronic use of aspirin ≤325 mg/day is allowed).
Azathioprine.
Mercaptopurine.
Theophylline.
Colchicine.
Pyrazinamide.
Sulfamethoxazole/trimethoprim.
Losartan.
The following restrictions also apply during the study:
Long-term use (more than 4 continuous weeks) of prescription or over-the-counter nonsterioidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors.
If receiving diuretics, participant must have been on a stable dose for at least 30 days prior to screening. No changes in dosage are allowed during the study.

Trial locations and contacts

28 sites in 1 country.

City, postcode or hospital

28 sites in 1 country

United States28 sites

Study site
Albuquerque, New Mexico
Study site
Anchorage, Alaska
Study site
Augusta, Georgia
Study site
Birmingham, Alabama
Study site
Boise, Idaho
Study site
Costa Mesa, California
Study site
Dallas, Texas
Study site
Denver, Colorado
Study site
East Providence, Rhode Island
Study site
Honolulu, Hawaii
Study site
Houston, Texas
Study site
Jackson, Mississippi
Study site
Kalamazoo, Michigan
Study site
Lexington, Kentucky
Study site
Meridian, Idaho
Study site
Miami, Florida
Study site
New Britain, Connecticut
Study site
New Windsor, New York
Study site
Orange, California
Study site
Palmdale, California
Study site
Poway, California
Study site
Rancho Cucamonga, California
Study site
San Diego, California
Study site
Santa Ana, California
Study site
Shelby, North Carolina
Study site
Sugar Land, Texas
Study site
Tucson, Arizona
Study site
Wilmington, North Carolina

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo and Allopurinol Controlled, Phase 2 Study to Evaluate Febuxostat in the Medical Management of Subjects With Hyperuricosuria and Calcium Oxalate Stones

Read the detailed description

Nephrolithiasis, also called kidney stone disease, occurs in patients with genetic susceptibility and who may have a broad spectrum of metabolic disorders and other comorbid conditions (for example obesity or diabetes). These renal stones develop as a result of supersaturation. Calcium oxalate (CaOx) is the most common type of stone. Reducing the urinary excretion of uric acid is an established approach for the treatment of CaOx kidney stones.

The objective of this study is to evaluate treatment with febuxostat compared to allopurinol or placebo in the reduction of 24-hour urine uric acid (uUA) excretion levels in hyperuricosuric patients with a recent history of renal stones and the presence of at least one CaOx stone larger than or equal to 3 mm as seen on Multidetector Computed Tomographic Angiography (MDCT).

Participants in this study will be required to make 4 office visits provide 3 urine samples and undergo 2 MDCT scans (a type of x-ray) of their kidneys.

Conditions: Hyperuricosuria, Kidney Stones
Being tested: Febuxostat, Allopurinol, Placebo
Keywords: Kidney Calculi, Kidney Stones, Nephrolithiasis, Drug Therapy, Uric Acid
Medical subject headings: Kidney Calculi, Nephrolithiasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FebuxostatDrug
Also called Uloric, TMX-67
Febuxostat capsules
AllopurinolDrug
Also called Zyloprim
Allopurinol capsules
PlaceboDrug
Placebo-matching capsules

Study groups in NCT01077284
Study group	Role	What they receive
Febuxostat	Experimental	Febuxostat 80 mg, capsules, orally, once daily for up to 6 months. Receives: Drug: Febuxostat
Allopurinol	Active comparator	Allopurinol 200mg or 300mg (determined by kidney function), capsules, orally, once daily for up to 6 months. Receives: Drug: Allopurinol
Placebo	Placebo comparator	Placebo-matching capsules, orally, once daily for up to 6 months. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion
The change from Baseline to Month 6 in 24-hour urine uric acid is expressed as a percentage of the Baseline uUA value.
Measured: Baseline and Month 6

Secondary outcomes (3)

Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone
Multidetector Computed Tomography (MDCT) was used to visualize and measure calcium oxalate kidney stones at Baseline and after 6 months of treatment. All MDCT images were analyzed independently by a Central Reader. The change from Baseline to month 6 is expressed as a percentage of the Baseline largest in-plane diameter.
Measured: Baseline and Month 6
Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones
Multidetector Computed Tomography (MDCT) was used to visualize and count calcium oxalate kidney stones at Baseline and after 6 months of treatment. All MDCT images were analyzed independently by a Central Reader.
Measured: Baseline and Month 6
Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance
Creatinine clearance is a measure of how well the kidneys are filtering creatinine, a waste product produced by the muscles. Measured creatinine clearance was calculated according to the following: Urine 24 hour Creatinine/Serum Creatinine x (total Urine volume/elapsed time) x (1.73/body surface area).
Measured: Baseline and Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2010Nov 2011

First posted1 Mar 2010 (estimated)
Study startFeb 2010
Primary completionNov 2011
Study completionNov 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HyperuricosuriaStudies of the same condition, open and under way.
More trials run by TakedaThe 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 99 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01077284
Sponsor's protocol ID: TMX-67_201
Other IDs: U1111-1113-6322
Status last verified: Jan 2013
First submitted: 25 Feb 2010
Last updated: 15 Feb 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Goldfarb DS, MacDonald PA, Gunawardhana L, Chefo S, McLean L. Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones. Clin J Am Soc Nephrol. 2013 Nov;8(11):1960-7. doi: 10.2215/CJN.01760213. Epub 2013 Aug 8.
PubMed 23929928

Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Randomized, Double-Blind, Placebo and Allopurinol Controlled, Phase 2 Study to Evaluate Febuxostat in the Medical Management of Subjects With Hyperuricosuria and Calcium Oxalate Stones
ClinicalTrials.gov ID: NCT01077284
Acronym / sponsor ID: TMX-67_201
Conditions: Hyperuricosuria, Kidney Stones
Keywords: Kidney Calculi, Kidney Stones, Nephrolithiasis, Drug Therapy, Uric Acid
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 99 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: Feb 2010
Primary completion: Nov 2011 (actual)
Study completion: Nov 2011 (actual)
First posted: 1 Mar 2010 (estimated)
Results: Posted 15 Feb 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Participants in this study will be required to make 4 office visits provide 3 urine samples and undergo 2 MDCT scans (a type of x-ray) of their kidneys.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Febuxostat	Experimental	Drug: FebuxostatFebuxostat 80 mg, capsules, orally, once daily for up to 6 months.
Allopurinol	Active comparator	Drug: AllopurinolAllopurinol 200mg or 300mg (determined by kidney function), capsules, orally, once daily for up to 6 months.
Placebo	Placebo comparator	Drug: PlaceboPlacebo-matching capsules, orally, once daily for up to 6 months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Has hyperuricosuria, defined as a daily urine uric acid excretion greater than 700 mg as measured by 24-hour urine collection prior to randomization.
Has at least one calcium oxalate stone greater than or equal to 3 mm in its longest in-plane diameter, identified by Multiple Detector Computated Tomography prior to randomization.
Has a recent (within the previous 5 years) history of renal stones prior to screening.

Key exclusion criteria (26 listed)

Has gout, secondary hyperuricemia or has experienced a gout flare.
Has a history of xanthinuria.
Has received allopurinol or probenecid within 2 years prior to randomization.
Has received febuxostat.
Has alanine aminotransferase and/or aspartate aminotransferase values greater than 2.0 times the upper limit of normal at the Screening Visit.

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
FebuxostatAlso: Uloric, TMX-67Febuxostat capsules	Drug	Febuxostat
AllopurinolAlso: ZyloprimAllopurinol capsules	Drug	Allopurinol
PlaceboPlacebo-matching capsules	Drug	Placebo

Primary outcome

Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion
Time frame: Baseline and Month 6
The change from Baseline to Month 6 in 24-hour urine uric acid is expressed as a percentage of the Baseline uUA value.

3 secondary outcomes

Percent Change From Baseline to Month 6 in the In-plane Diameter of the Largest Calcium Oxalate (CaOx) Stone
Time frame: Baseline and Month 6
Change From Baseline to Month 6 in the Number of Calcium Oxalate Stones
Time frame: Baseline and Month 6
Change From Baseline to Month 6 in 24-hour Measured Creatinine Clearance
Time frame: Baseline and Month 6

Results and safety

Results posted to the registry on 15 Feb 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Febuxostat	33	28
Allopurinol	33	28
Placebo	33	30

Primary outcome: Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion

Time frame: Baseline and Month 6. Mean (Standard Deviation). Unit: percent change

Measure	Febuxostat n = 33	Allopurinol n = 33	Placebo n = 33
Value	-58.6 (28.56)	-36.4 (36.97)	-12.7 (28.81)

Febuxostat vs Placebo: p <0.001, Wilcoxon (Mann-Whitney)
Febuxostat vs Allopurinol: p = 0.003, Wilcoxon (Mann-Whitney)

Population analysed: The full analysis set (patients who took at least 1 dose of double-blind study drug and had a baseline 24-hour uUA \>700 mg and at least 1 kidney CaOx stone ≥3 mm in its longest inplane diameter). Missing Month 6 values were imputed with baseline values if patient discontinued due to an AE; or otherwise with the last available post-baseline value.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment emergent AEs were defined as any AE, regardless of relationship to study drug, which occurred on or after the first double blind dose date and up to 30 days after the last dose date of the double-blind study drug (up to 7 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Febuxostat	0 of 33 (0%)	14 of 33 (42.4%)	Not reported
Allopurinol	0 of 33 (0%)	13 of 33 (39.4%)	Not reported
Placebo	1 of 33 (3%)	12 of 33 (36.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23929928Goldfarb DS, MacDonald PA, Gunawardhana L, Chefo S, McLean L. Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones. Clin J Am Soc Nephrol. 2013 Nov;8(11):1960-7. doi: 10.2215/CJN.01760213. Epub 2013 Aug 8.
Uloric Package InsertLink provided by the sponsor.

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.

Senior Medical Director Clinical Science study director

Takeda

28 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Febuxostat and Allopurinol in people with Hyperuricosuria and Kidney Stones, run by Takeda at 28 sites in United States.

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 26 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 15 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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?

Yes. Results are posted in the registry (first posted 15 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percent Change From Baseline to Month 6 in 24-hour Urine Uric Acid (uUA) Excretion (time frame: Baseline and Month 6). 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 NCT01077284, which also lists 1 linked publication.

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 15 Feb 2013.