A study to assess the effect of intensive uric acid (UA) lowering therapy with RDEA3170, febuxostat, dapagliflozin on urinary excretion of UA

Study identifier:D5495C00001

ClinicalTrials.gov identifier:NCT03316131

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Quantifying Uric Acid Excretion with RDEA3170, Febuxostat and Dapagliflozin

Medical condition

Asymptomatic hyperuricemia

Phase

Phase 2

Healthy volunteers

Study drug

Verinurad, Febuxostat, Dapagliflozin

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 25 Oct 2017

Primary Completion Date: 19 Jul 2018

Study Completion Date: 19 Jul 2018

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Crossover Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2019 by AstraZeneca

Collaborators

Contract Research Organization: USA, PAREXEL Early Phase Clinical Unit Baltimore, PAREXEL Early Phase Clinical Unit-Los Angeles, Clinical Laboratory: USA, Harbor Hospital Laboratory, GenX Laboratories Inc., Analytical Laboratory (Pharmacokinetic Sample Analysis): USA, Covance Bioanalytical Services, LLC

Inclusion and exclusion criteria

This is a randomized, placebo controlled, double-blind, 2-way crossover study to assess the effect of intensive UA lowering therapy with verinurad (RDEA3170), febuxostat, and dapagliflozin on urinary excretion of UA, in asymptomatic hyperuricemic patients. Thirty-six asymptomatic hyperuricemic patients aged 18 to 65 years (inclusive) will be enrolled into this study at 2 study centers. Twenty-four patients have been enrolled and completed the study to date. Due to inadequate urine sampling, 12 additional patients were included to ensure an adequate sample size (at least 20 evaluable patients) to evaluate the effects of intensive UA lowering with verinurad, febuxostat and dapagliflozin on urinary excretion of UA. With 24 completers available during the interim analysis, this will provide for a total sample size of 36 evaluable patients. Before any study specific assessments are performed, potential patients must provide informed consent. Each patient will undergo the below mentioned visits: • A Screening period of maximum 28 days; • Two treatment periods during which patients will be resident in the Clinical Unit from Day -2 to Day 1 and from Day 6 to Day 8; and • A Follow-up Visit within 14 to 28 days after the first administration of Investigational Medicinal Product (IMP) in Treatment Period 2. On Day -2 of Treatment period 1, patient will be randomized (1:1) to 1 of 2 treatment sequences (AB or BA). Each randomized patient will receive orally once daily fixed dose of the below mentioned 2 treatments for 7 consecutive days (1 treatment per treatment period). •Treatment A: Verinurad + febuxostat + dapagliflozin •Treatment B: Verinurad + febuxostat + placebo For each treatment period, baseline measurements will be performed. On Day 1, after all dosing and all assessments have been performed, patients will receive instruction to administer the IMP at home once daily in the morning from Day 2 to Day 6 and the IMP will be dispensed for home dosing. Patients will return to the Clinical Unit on Day 6 and will be residential in the Clinical Unit from Day 6 to Day 8. Treatment Period 1 and Treatment Period 2 will be separated by a washout period of 7 to 21 days. Patients will return to the Clinical Unit for a Follow-up Visit, 14 to 28 days after Day 1 of Treatment Period 2.

Location

Research Site

Baltimore, MD, United States, 21225

Location

Research Site

Glendale, CA, United States, 91206

Arms	Assigned Interventions
Experimental: Treatment A Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin;	Drug: Verinurad 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 Other Name: RDEA3170 Drug: Febuxostat 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 Other Name: ULORIC Drug: Dapagliflozin 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 Other Name: FARXIGA
Experimental: Treatment B Randomized patients will receive orally once daily fixed dose of the following drugs: verinurad + febuxostat + dapagliflozin matched placebo	Drug: Verinurad 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 Other Name: RDEA3170 Drug: Febuxostat 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 Other Name: ULORIC Other: Dapagliflozin matched placebo 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

Arms

Assigned Interventions

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

Drug: Verinurad
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

Other Name: RDEA3170

Drug: Febuxostat
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

Other Name: ULORIC

Drug: Dapagliflozin
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

Other Name: FARXIGA

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

Other Name: RDEA3170

Other Name: ULORIC

Other: Dapagliflozin matched placebo
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

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The trial was conducted at two study centres: Baltimore and Los Angeles. The date of the first subject visit was 25 Oct 2017 and the date of the last subject last visit was 19 Jul 2018. A total of 36 adults asymptomatic hyperuricemic patients were included into this study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients who provided informed consent underwent screening procedures within the 28 days. Patients returned to the Clinical Unit on Day -2 of Treatment Period 1 and were randomized (1:1) to two treatment sequences ( treatment AB or BA).

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Participant Flow for 2 periods

Period 1: Treatment period 1

	Treatment Sequence A+B	Treatment Sequence B+A
STARTED	18	18
COMPLETED	18	18
NOT COMPLETED	0	0

Period 2: Treatment period 2

	Treatment Sequence A+B	Treatment Sequence B+A
STARTED	18	18
COMPLETED	17	18
NOT COMPLETED	1	0
Protocol deviation	1	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
All Subjects	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin/placebo. Each patient randomized to treatment A in period 1 received Treatment B in period 2 and each patient randomized to treatment B in period 1 received Treatment A in period 2

Baseline Measures

	All Subjects
Number of Participants [units: Participants]	36
Age Continuous [units: years] Mean ± Standard Deviation	42.3 ± 12.01
Sex: Female, Male [units: ]
Female	1
Male	35
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0
Asian	2
Native Hawaiian or Other Pacific Islander	0
Black or African American	17
White	14
More than one race	3
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Change from baseline in peak urinary excretion of uric acid (UA) on Day 7 [ Time Frame: On Day -1 and Day 7 of each treatment period ]

Measure Type	Primary
Measure Name	Change from baseline in peak urinary excretion of uric acid (UA) on Day 7
Measure Description	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.
Time Frame	On Day -1 and Day 7 of each treatment period
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Protocol Analysis Set

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Measured Values

	Treatment Sequence A+B	Treatment Sequence B+A
Number of Participants Analyzed [units:participants]	36	36
Change from baseline in peak urinary excretion of uric acid (UA) on Day 7 [units: milligrams (mg)] Least Squares Mean (95% Confidence Interval)	-12.87 (-21.03 to -4.70)	-13.15 (-21.31 to -4.98)

Statistical Analysis 1 for Change from baseline in peak urinary excretion of uric acid (UA) on Day 7

Groups^[1]	All groups
Mean Difference (Net)^[5]	0.28
95% Confidence Interval	( -8.67 to 9.22 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Change from baseline in plasma concentration (Cmax) on Day 7 [ Time Frame: 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) ]

Measure Type	Primary
Measure Name	Change from baseline in plasma concentration (Cmax) on Day 7
Measure Description	Cmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Measured Values

	Treatment Sequence A+B	Treatment Sequence B+A
Number of Participants Analyzed [units:participants]	36	36
Change from baseline in plasma concentration (Cmax) on Day 7 [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Verinurad	17.52 (45.87%)	15.26 (52.48%)
M1	25.28 (41.55%)	25.61 (57.24%)
M8	18.45 (35.45%)	18.42 (44.36%)

Statistical Analysis 1 for Change from baseline in plasma concentration (Cmax) on Day 7

Groups^[1]	All groups
Other^[5]	1.14
90% Confidence Interval	( 1.03 to 1.25 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for Verinurad
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline in plasma concentration (Cmax) on Day 7

Groups^[1]	All groups
Other^[5]	0.97
90% Confidence Interval	( 0.88 to 1.07 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for M1
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change from baseline in plasma concentration (Cmax) on Day 7

Groups^[1]	All groups
Other^[5]	0.99
90% Confidence Interval	( 0.91 to 1.08 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for M8
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Change from baseline in area under plasma concentration time curve from time zero to the time of last measurable concentration (AUClast) on Day 7 [ Time Frame: 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) ]

Measure Type	Primary
Measure Name	Change from baseline in area under plasma concentration time curve from time zero to the time of last measurable concentration (AUClast) on Day 7
Measure Description	AUClast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Measured Values

	Treatment Sequence A+B	Treatment Sequence B+A
Number of Participants Analyzed [units:participants]	36	36
Change from baseline in area under plasma concentration time curve from time zero to the time of last measurable concentration (AUClast) on Day 7 [units: h∙ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Verinurad	149.1 (37.79%)	141.0 (44.90%)
M1	212.7 (42.74%)	221.3 (49.13%)
M8	174.2 (34.57%)	176.5 (36.85%)

Statistical Analysis 1 for Change from baseline in area under plasma concentration time curve from time zero to the time of last measurable concentration (AUClast) on Day 7

Groups^[1]	All groups
Other^[5]	1.06
90% Confidence Interval	( 1.00 to 1.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for Verinurad
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline in area under plasma concentration time curve from time zero to the time of last measurable concentration (AUClast) on Day 7

Groups^[1]	All groups
Other^[5]	0.96
90% Confidence Interval	( 0.90 to 1.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for M1
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change from baseline in area under plasma concentration time curve from time zero to the time of last measurable concentration (AUClast) on Day 7

Groups^[1]	All groups
Other^[5]	0.99
90% Confidence Interval	( 0.94 to 1.04 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for M8
[5]	Other relevant estimation information:
	No text entered.

4. Primary Outcome Measure: Change from baseline in area under plasma concentration time curve over a dosing interval (24 hours) (AUCτ) on Day 7 [ Time Frame: 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) ]

Measure Type	Primary
Measure Name	Change from baseline in area under plasma concentration time curve over a dosing interval (24 hours) (AUCτ) on Day 7
Measure Description	AUCτ assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Measured Values

	Treatment Sequence A+B	Treatment Sequence B+A
Number of Participants Analyzed [units:participants]	36	36
Change from baseline in area under plasma concentration time curve over a dosing interval (24 hours) (AUCτ) on Day 7 [units: h∙ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Verinurad	149.0 (37.84%)	140.9 (44.90%)
M1	212.6 (42.78%)	221.1 (49.13%)
M8	174.1 (34.59%)	176.3 (36.81%)

Statistical Analysis 1 for Change from baseline in area under plasma concentration time curve over a dosing interval (24 hours) (AUCτ) on Day 7

Groups^[1]	All groups
Other^[5]	1.06
90% Confidence Interval	( 1.00 to 1.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for Verinurad
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline in area under plasma concentration time curve over a dosing interval (24 hours) (AUCτ) on Day 7

Groups^[1]	All groups
Other^[5]	0.96
90% Confidence Interval	( 0.90 to 1.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for M1
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change from baseline in area under plasma concentration time curve over a dosing interval (24 hours) (AUCτ) on Day 7

Groups^[1]	All groups
Other^[5]	0.99
90% Confidence Interval	( 0.94 to 1.04 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Treatment A/Treatment B, for M8
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Change from baseline in urinary excretion of serum UA (sUA) on Day 7 [ Time Frame: At Day -1 and Day 7 ]

Measure Type	Secondary
Measure Name	Change from baseline in urinary excretion of serum UA (sUA) on Day 7
Measure Description	Change from baseline in sUA to assess the intensive UA lowering effect of RDEA3170, febuxostat and dapagliflozin by evaluating the sUA levels after 7 days of treatment.
Time Frame	At Day -1 and Day 7
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacodynamic Analysis Set

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Measured Values

	Treatment Sequence A+B	Treatment Sequence B+A
Number of Participants Analyzed [units:participants]	36	36
Change from baseline in urinary excretion of serum UA (sUA) on Day 7 [units: umol/L] Least Squares Mean (95% Confidence Interval)	-327.161 (-352.559 to -301.762)	-264.851 (-290.060 to -239.643)

No statistical analysis provided for Change from baseline in urinary excretion of serum UA (sUA) on Day 7

6. Secondary Outcome Measure: Change from baseline in time to reach maximum observed concentration (tmax) on Day 7 [ Time Frame: 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) ]

Measure Type	Secondary
Measure Name	Change from baseline in time to reach maximum observed concentration (tmax) on Day 7
Measure Description	tmax assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Measured Values

	Treatment Sequence A+B	Treatment Sequence B+A
Number of Participants Analyzed [units:participants]	36	36
Change from baseline in time to reach maximum observed concentration (tmax) on Day 7 [units: hour] Median (Full Range)
Verinurad	4.00 (2.00 to 8.00)	4.00 (3.00 to 8.08)
M1	4.00 (2.00 to 8.00)	4.00 (3.00 to 4.03)
M8	4.00 (3.00 to 8.02)	4.00 (3.00 to 8.08)

No statistical analysis provided for Change from baseline in time to reach maximum observed concentration (tmax) on Day 7

7. Secondary Outcome Measure: Change from baseline in time of last measurable concentration (tlast) on Day 7 [ Time Frame: 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) ]

Measure Type	Secondary
Measure Name	Change from baseline in time of last measurable concentration (tlast) on Day 7
Measure Description	tlast assessment for Verinurad, M1, and M8 following daily oral administration of verinurad and febuxostat with and without dapagliflozin
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic Analysis Set

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Measured Values

	Treatment Sequence A+B	Treatment Sequence B+A
Number of Participants Analyzed [units:participants]	36	36
Change from baseline in time of last measurable concentration (tlast) on Day 7 [units: hour] Median (Full Range)
Verinurad	24.00 (23.85 to 24.47)	24.00 (23.22 to 24.40)
M1	24.00 (23.85 to 24.47)	24.00 (23.22 to 24.40)
M8	24.00 (23.85 to 24.47)	24.00 (23.22 to 24.40)

No statistical analysis provided for Change from baseline in time of last measurable concentration (tlast) on Day 7

Serious Adverse Events

Time Frame	Adverse events were collected from the start of randomization throughout the treatment period up to and including the Follow-up Visit. Serious adverse events were recorded from the time of informed consent.
Additional Description	From screening (Day -28) to follow-up (Day 23)

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study

Serious Adverse Events

	Treatment Sequence A+B	Treatment Sequence B+A
Total, serious adverse events
# participants affected / at risk	0/35 (0.00%)	0/36 (0.00%)

Other Adverse Events

Time Frame	Adverse events were collected from the start of randomization throughout the treatment period up to and including the Follow-up Visit. Serious adverse events were recorded from the time of informed consent.
Additional Description	From screening (Day -28) to follow-up (Day 23)

Frequency Threshold

Threshold above which other adverse events are reported	1%

Reporting Groups

	Description
Treatment Sequence A+B	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + 10 mg dapagliflozin (Treatment A). Each patient randomized to treatment A in period 1 received Treatment B in period 2 as this is 2-way crossover study
Treatment Sequence B+A	Each patient received orally once daily dose of 9 mg verinurad + 80 mg febuxostat + placebo (Treatment B). Each patient randomized to treatment B in period 1 received Treatment A in period 2 as this is 2-way crossover study