NCT03316131

Brief Summary

This is a randomized, placebo controlled, double-blind, 2-way crossover study conducted on asymptomatic hyperuricemic patients. The core study consists of screening period, 2 treatment periods (verinurad + febuxostat + dapagliflozin/placebo) and follow-up visit

Trial Health

87
On Track

Trial Health Score

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

Enrollment
36

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Oct 2017

Shorter than P25 for phase_2

Geographic Reach
1 country

2 active sites

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

First Submitted

Initial submission to the registry

October 17, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 20, 2017

Completed
5 days until next milestone

Study Start

First participant enrolled

October 25, 2017

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 19, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 19, 2018

Completed
12 months until next milestone

Results Posted

Study results publicly available

July 18, 2019

Completed
Last Updated

August 28, 2019

Status Verified

August 1, 2019

Enrollment Period

9 months

First QC Date

October 17, 2017

Results QC Date

June 27, 2019

Last Update Submit

August 14, 2019

Conditions

Asymptomatic Hyperuricemia

Keywords

GoutUric acidHyperuricemiaAsymptomatic goutFebuxostatDapagliflozinUric acid transporter 1 (URAT1) InhibitorXanthine Oxidase InhibitorSodium-glucose cotransporter 2 (SGLT2) Inhibitor

Outcome Measures

Primary Outcomes (4)

  • Change From Baseline in Peak Urinary Excretion of Uric Acid (UA) on Day 7

    Change from baseline in peak UA excretion during the first 8 hours on Day 7 of treatment to assess the effects of intensive UA lowering therapy with verinurad, febuxostat and dapagliflozin. Urine sample was collected in hourly intervals, and the highest amount of UA excreted in any interval was designated as peak UA excretion for each patient and treatment period.

    On Day -1 and Day 7 of each treatment period

  • Change From Baseline in Plasma Concentration (Cmax) on Day 7

    Cmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin

    On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose)

  • Change From Baseline in Area Under Plasma Concentration Time Curve From Time Zero to the Time of Last Measurable Concentration (AUClast) on Day 7

    AUClast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin

    On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose)

  • Change From Baseline in Area Under Plasma Concentration Time Curve Over a Dosing Interval (24 Hours) (AUCτ) on Day 7

    AUCτ assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin

    On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose)

Secondary Outcomes (3)

  • Change From Baseline in Urinary Excretion of Serum UA (sUA) on Day 7

    At Day -1 and Day 7

  • Change From Baseline in Time to Reach Maximum Observed Concentration (Tmax) on Day 7

    On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose)

  • Change From Baseline in Time of Last Measurable Concentration (Tlast) on Day 7

    On Treatment Period 1 and 2: Day 7 (Pre-dose and 15 minutes, 30 minutes, 1 hour, 1.5, 2, 3, 4, 8, 12 and 24 hours post-dose)

Study Arms (2)

Treatment A

EXPERIMENTAL

Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin;

Drug: VerinuradDrug: FebuxostatDrug: Dapagliflozin

Treatment B

EXPERIMENTAL

Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin matched placebo

Drug: VerinuradDrug: FebuxostatOther: Dapagliflozin matched placebo

Interventions

VerinuradDRUG

Randomized patients will receive orally once daily fixed dose of verinurad in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo

Also known as: RDEA3170
Treatment ATreatment B
FebuxostatDRUG

Randomized patients will receive orally once daily fixed dose of febuxostat in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo

Also known as: ULORIC
Treatment ATreatment B
DapagliflozinDRUG

Randomized patients will receive orally once daily fixed dose of dapagliflozin in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo

Also known as: FARXIGA
Treatment A
Dapagliflozin matched placeboOTHER

Randomized patients will receive orally once daily fixed dose of dapagliflozin matched placebo in 2 treatment sequences AB or BA for 7 consecutive days. Treatment A: verinurad + febuxostat + dapagliflozin; Treatment B: verinurad + febuxostat + placebo

Treatment B

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • to 65 years old
  • Asymptomatic hyperuricemia (sUA \> 6.0 mg/dL)
  • Body mass index between 18 and 35 kg/m2 inclusive and weight at least 50 kg and no more than 150 kg
  • Females must be non-pregnant, as well as post-menopausal or willing to use an acceptable method of contraception during the study.

You may not qualify if:

  • History of any clinically significant disease or disorder putting the patient at risk during the study, or influencing study results or ability to participate in the study
  • eGFR\* \< 45 mL/minute/1.73 m2 at Screening.
  • Type 2 diabetes mellitus with HbA1c \>8%.
  • History of diabetic ketoacidosis, hyperosmolar non-ketotic coma, gout, or alcohol or drug abuse.
  • Ongoing treatment with an SGLT2-inhibitor, a URAT1-inhibitor, and/or a xanthine oxidase inhibitor.
  • Positive test for hepatitis B, hepatitis C or HIV.
  • Use of any medications in the 2 weeks preceding first administration of study drug.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Research Site

Glendale, California, 91206, United States

Location

Research Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

  • Stack AG, Han D, Goldwater R, Johansson S, Dronamraju N, Oscarsson J, Johnsson E, Parkinson J, Erlandsson F. Dapagliflozin Added to Verinurad Plus Febuxostat Further Reduces Serum Uric Acid in Hyperuricemia: The QUARTZ Study. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2347-e2356. doi: 10.1210/clinem/dgaa748.

    PMID: 33075806DERIVED

Related Links

MeSH Terms

Conditions

GoutHyperuricemia

Interventions

verinuradFebuxostatdapagliflozin

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 DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

The initial plan was to recruit 24 patients, but due to difficulties in determining the peak urinary uric acid excretion in 11 patients, it was decided to include 12 additional patients to ensure adequate sample size.

Results Point of Contact

Title
Fredrik Erlandsson
Organization
AstraZeneca RD, Gothenburg
information.center@astrazeneca.com
1-877-240-9479

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
The pharmacokineticist will remain blinded during the study conduct, unless otherwise required based on study findings. The pharmacokineticist will be unblinded to perform the final PK analyses after all patients have completed the study, final bioanalytical results are available and all required study data are considered clean. This may occur before database lock.
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 17, 2017

First Posted

October 20, 2017

Study Start

October 25, 2017

Primary Completion

July 19, 2018

Study Completion

July 19, 2018

Last Updated

August 28, 2019

Results First Posted

July 18, 2019

Record last verified: 2019-08

Data Sharing

IPD Sharing
Will not share

Locations

US(2)