A Study to Assess the Relative Bioavailability of 3 Different Formulations Under Fasted and Fed Condition

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04024501
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arms: 5
• Actual Duration (Months): 2
• Patients Per Site Per Month: 12.7

Study Details

Study Description

Brief Summary

This study is intended to assess the relative bioavailability between the (extended-release) ER8 capsule formulation (the formulation that is currently used for verinurad development) given under fasted conditions and 2 new capsule formulations of verinurad (A-capsule and B-capsule) given under fed or fasted conditions. All three capsules target an 8-hour release profile (extended-release). The highest dose (12 mg) currently tested in participants will be tested in this study. The study is designed to provide information to optimize the verinurad part of a fixed dose combination capsule to be used in future development.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Drug: Verinurad ER8 capsule formulation (fasted); Drug: Verinurad A-capsule formulation (fasted); Drug: Verinurad A-capsule formulation (fed); Drug: Verinurad B-capsule formulation (fasted); Drug: Verinurad B-capsule formulation (fed)	Phase 1

Detailed Description

This study will be a randomised, open-label, single-dose, 5-period, 5-treatment, crossover study in healthy male and female participants, performed at a single study centre. This study is intended to assess the relative bioavailability between the ER8 capsule formulation (the formulation that is currently used for verinurad development) given under fasted conditions and 2 new capsule formulation of verinurad (A-capsule and B-capsule) given under fed or fasted conditions. All three capsules target an 8-hour release profile (extended-release). The highest dose (12 mg) currently tested in participants will be tested in this study. The study is designed to provide information to optimize the verinurad part of a fixed dose combination capsule to be used in future development. The study will comprise: a screening period of maximum 28 days; five treatment periods during which participants will be resident from the morning of the day before dosing with verinurad (Day -1) until at least 72 hours after dosing; discharged on the morning of Day 4 of each Treatment Period; and a follow-up Visit within 7 to 14 days after the last administration of verinurad. There will be a minimum washout period of 5 days between each dose administration. A total of 25 healthy male and female participants will be randomised into this study. Each participant will receive five single-dose treatments of 12 mg verinurad with 240 mL water, following an overnight fast of at least 10 hours. Participants will follow an overnight fast of at least 10 hours before the dosing procedures: for the fed dosing, a high-fat, high-calorie standard breakfast will be served 30 minutes before the planned administration of verinurad to be consumed in full at least 5 minutes before dosing; for the fasted dosing, no breakfast will be served. A meal can be given 4 hours after administration of verinurad for both dosing states. The duration of the study is expected to be approximately 9 weeks for each individual participant (including the 28-day screening period).

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Single-dose, 5-period, 5-treatment, Crossover Study to Assess the Relative Bioavailability of 3 Different Extended-release Formulations of Verinurad in Healthy Subjects
• Actual Study Start Date: Jul 20, 2019
• Actual Primary Completion Date: Sep 18, 2019
• Actual Study Completion Date: Sep 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment 1 During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	Drug: Verinurad ER8 capsule formulation (fasted); Each participant will receive single-dose treatment of 12 mg verinurad ER8 capsule with 240 mL water, following an overnight fast of at least 10 hours.
Experimental: Treatment 2 During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	Drug: Verinurad A-capsule formulation (fasted); Each participant will receive single-dose treatment of 12 mg verinurad A-capsule with 240 mL water, following an overnight fast of at least 10 hours.
Experimental: Treatment 3 During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	Drug: Verinurad A-capsule formulation (fed); Each participant will receive single dose treatment of 12 mg verinurad A-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).
Experimental: Treatment 4 During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	Drug: Verinurad B-capsule formulation (fasted); Each participant will receive single-dose treatment of 12 mg verinurad B-capsule with 240 mL water, following an overnight fast of at least 10 hours.
Experimental: Treatment 5 During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.	Drug: Verinurad B-capsule formulation (fed); Each participant will receive single dose treatment of 12 mg verinurad B-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).

Outcome Measures

Primary Outcome Measures

1. Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC) [Day 1: Pre-dose and up to 72-hour Post-dose]

   To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.

2. AUC From Time 0 to the Last Quantifiable Concentration (AUC0-t) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.

3. Maximum Observed Plasma Concentration (Cmax) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.

Secondary Outcome Measures

1. AUC From Time 0 to 24 Hours Post Dose (AUC0-24) for the Analysis of PK Parameter [Pre-dose and up to 24-hours Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

2. Time to Reach Maximum Observed Plasma Concentration (Tmax) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

3. Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

4. Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

5. Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

6. Time of Last Quantifiable Plasma Concentration (Tlast) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

7. Volume of Distribution at Steady State (Intravenous Dosing) (Vss/F) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

8. Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for the Analysis of PK Parameter [Day 1: Pre-dose and up to 72-hour Post-dose]

   To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.

9. Number of Participants With Adverse Events (AEs) [From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose)]

   To assess AEs as variable of safety and tolerability of single doses of verinurad in healthy participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific procedures.

2. Healthy male and female participants aged 18 to 50 years with suitable veins for cannulation or repeated venepuncture.

3. Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg.

4. Females must have a negative pregnancy test at screening and on admission to the unit and must be:

(1) not pregnant or currently lactating or breastfeeding. (2) of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria: (i) postmenopausal defined as amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range (FSH levels > 40 IU/mL).

(ii) documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

(3) OR if of childbearing potential must be willing to use an acceptable method of contraception to avoid pregnancy for the entire study period.

Exclusion Criteria:

1. History of gout or any clinically significant disease or disorder which, in the opinion of the Principal Investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.

2. Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of verinurad.

3. History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.

4. Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results as judged by the Investigator at screening and first admission, including: (1) Alanine aminotransferase (ALT) > 1.5 x upper limit of normal (ULN), (2) Aspartate aminotransferase (AST) > 1.5 x ULN, (3) Bilirubin (total) > 1.5 x ULN, (4) Gamma glutamyl transpeptidase (GGT) > 1.5 x ULN. (5) If any of these tests are out-of-range, the tests can be repeated once.

5. Any clinically significant abnormal findings in vital signs at the Screening Visit and/or admission to the Clinical Unit, including, but not limited to, any of the following:

(1) Heart rate (resting, supine) < 50 beats per minute (bpm) or > 85 bpm, (2) Systolic BP < 90 mmHg or > 140 mmHg and/or diastolic BP < 50 mmHg or > 90 mmHg sustained for > 10 min while resting in a supine position.

1. Any clinically significant abnormalities on 12-lead Electrocardiogram (ECG) at the

Screening Visit, including, but not limited to any of the following:

1. ECG interval measured from the onset of the QRS complex to the end of the T wave (QT) interval corrected for heart rate using Fridericia's formula (QTcF) > 450 ms or < 340 ms or family history of long QT syndrome,

2. Any significant arrhythmia,

3. Conduction abnormalities:

4. Clinically significant PR (PQ) interval prolongation (> 240 ms); intermittent second or third degree atrioventricular (AV) block, or AV dissociation,

5. Complete bundle branch block and/or QRS duration > 120 ms. 7. Any positive result at the Screening Visit for serum hepatitis B surface antigen or antiHBc antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

6. Suspicion or known Gilbert's and/or Lesch-Nyhan syndrome. 9. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g of alcohol per day for women.

7. Has received another new chemical entity (defined as a compound which has not been approved for marketing in the US) within 30 days or at least 5 half-lives (whichever is longer) of the first administration of verinurad in this study.

8. Participants who have previously received verinurad. 12. Plasma donation within 1 month of screening or any blood donation/loss of more than 500 mL during the 3 months prior to the Screening Visit.

9. Participants who are pregnant, lactating or planning to become pregnant. 14. History of severe allergy/hypersensitivity or ongoing clinically relevant allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to verinurad.

10. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.

11. Excessive intake of caffeine-containing drinks or food (e.g., coffee, tea, chocolate) as judged by the PI. Excessive intake of caffeine defined as regular consumption of more than 600 mg of caffeine per day (e.g., > 5 cups of coffee) or would likely be unable to refrain from the use of caffeine containing beverages during confinement at the investigational site.

12. Positive screen for drugs of abuse or cotinine (nicotine) at the Screening Visit or positive screen for alcohol, drugs of abuse and cotinine on each admission to the study centre.

13. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of verinurad.

14. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of verinurad or longer if the medication has a long half-life. The use of hormonal contraception therapy and hormonal replacement therapy for females are permitted.

15. Any AstraZeneca, PAREXEL or study site employee or their close relatives. 21. Participants who cannot communicate reliably with the PI and/or is not able to read, speak and understand the German language.

16. Judgment by the PI that the participant should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.

17. Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

18. Participants with any special dietary restrictions such as participants that are lactose intolerant or are vegetarians/vegans.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Berlin		Germany	14050

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 24, 2019

More Information

Additional Information:

• redacted CSP and SAP

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04024501
• Other Study ID Numbers: D5495C00005
• First Posted: Jul 18, 2019
• Last Update Posted: Mar 18, 2021
• Last Verified: Feb 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: URAT1 inhibitor; Uric acid transporter 1; Verinurad; Crossover study; Relative bioavailability; Pharmacokinetics
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Verinurad

Study Results

Participant Flow

Recruitment Details	All subjects signed and dated the informed consent form (ICF) before any study procedures were performed.
Pre-assignment Detail	The study included a Screening Period of maximum 28 days.

Arm/Group Title	Overall-All Subjects
Arm/Group Description	All subjects were randomized into 5-period, 5-treatment, crossover study to receive a single oral dose of 12 mg verinurad: Treatment 1: 1 x 12 mg verinurad ER8 capsule formulation, fasted. Treatment 2: 2 x 6 mg verinurad A-capsule formulation, fasted. Treatment 3: 2 x 6 mg verinurad A-capsule formulation, fed. Treatment 4: 2 x 6 mg verinurad B-capsule formulation, fasted. Treatment 5: 2 x 6 mg verinurad B-capsule formulation, fed.
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Overall-All Subjects
Arm/Group Description	All subjects were randomized into 5-period, 5-treatment, crossover study to receive a single oral dose of 12 mg verinurad: Treatment 1: 1 x 12 mg verinurad ER8 capsule formulation, fasted. Treatment 2: 2 x 6 mg verinurad A-capsule formulation, fasted. Treatment 3: 2 x 6 mg verinurad A-capsule formulation, fed. Treatment 4: 2 x 6 mg verinurad B-capsule formulation, fasted. Treatment 5: 2 x 6 mg verinurad B-capsule formulation, fed.
Overall Participants	25
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.1 (9.4)
Sex: Female, Male (Count of Participants)
Female	11 44%
Male	14 56%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	25 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	25 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC)
Description	To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	171.3 (47.60)	167.5 (33.72)	87.14 (65.84)	149.0 (39.78)	150.2 (42.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 2: 2 x 6 mg A-capsule Fasted
	Comments	Pairwise comparison: Treatment 2/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean ratio
	Estimated Value	106.20
	Confidence Interval	(2-Sided) 90%; 91.73 to 122.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
	Comments	Pairwise comparison: Treatment 3/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	50.02
	Confidence Interval	(2-Sided) 90%; 42.34 to 59.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
	Comments	Pairwise comparison: Treatment 3/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	47.10
	Confidence Interval	(2-Sided) 90%; 39.85 to 55.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 3/Treatment 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	58.40
	Confidence Interval	(2-Sided) 90%; 49.49 to 68.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 4/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	85.65
	Confidence Interval	(2-Sided) 90%; 73.78 to 99.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 4/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	80.65
	Confidence Interval	(2-Sided) 90%; 69.48 to 93.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	89.88
	Confidence Interval	(2-Sided) 90%; 77.61 to 104.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	84.64
	Confidence Interval	(2-Sided) 90%; 72.94 to 98.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	179.68
	Confidence Interval	(2-Sided) 90%; 151.57 to 212.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Treatment 4: 2 x 6 mg B-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	104.94
	Confidence Interval	(2-Sided) 90%; 90.18 to 122.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUC From Time 0 to the Last Quantifiable Concentration (AUC0-t) for the Analysis of PK Parameter
Description	To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	166.8 (47.57)	167.5 (35.96)	67.04 (80.37)	128.5 (49.29)	139.6 (44.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 2: 2 x 6 mg A-capsule Fasted
	Comments	Pairwise comparison: Treatment 2/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	100.39
	Confidence Interval	(2-Sided) 90%; 84.94 to 118.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
	Comments	Pairwise comparison: Treatment 3/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	41.26
	Confidence Interval	(2-Sided) 90%; 34.74 to 49.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
	Comments	Pairwise comparison: Treatment 3/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	41.10
	Confidence Interval	(2-Sided) 90%; 34.61 to 48.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 3/Treatment 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	53.55
	Confidence Interval	(2-Sided) 90%; 45.09 to 63.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 4/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	77.05
	Confidence Interval	(2-Sided) 90%; 65.19 to 91.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 4/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	76.75
	Confidence Interval	(2-Sided) 90%; 64.94 to 90.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	84.23
	Confidence Interval	(2-Sided) 90%; 70.93 to 100.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	83.90
	Confidence Interval	(2-Sided) 90%; 70.65 to 99.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	204.16
	Confidence Interval	(2-Sided) 90%; 171.22 to 243.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Treatment 4: 2 x 6 mg B-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	109.32
	Confidence Interval	(2-Sided) 90%; 92.06 to 129.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) for the Analysis of PK Parameter
Description	To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	25.51 (53.66)	31.88 (62.41)	8.243 (81.12)	23.39 (66.08)	17.02 (54.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 2: 2 x 6 mg A-capsule Fasted
	Comments	Pairwise comparison: Treatment 2/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	124.99
	Confidence Interval	(2-Sided) 90%; 101.09 to 154.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
	Comments	Pairwise comparison: Treatment 3/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	33.77
	Confidence Interval	(2-Sided) 90%; 27.15 to 42.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 3: 2 x 6 mg A-capsule Fed
	Comments	Pairwise comparison: Treatment 3/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	27.02
	Confidence Interval	(2-Sided) 90%; 21.72 to 33.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 3/Treatment 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	36.84
	Confidence Interval	(2-Sided) 90%; 29.61 to 45.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 4/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	91.69
	Confidence Interval	(2-Sided) 90%; 74.15 to 113.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 4: 2 x 6 mg B-capsule Fasted
	Comments	Pairwise comparison: Treatment 4/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	73.36
	Confidence Interval	(2-Sided) 90%; 59.33 to 90.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment 1: 1 x 12 mg ER8 Capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	67.62
	Confidence Interval	(2-Sided) 90%; 54.37 to 84.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Treatment 2: 2 x 6 mg A-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 2
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	54.11
	Confidence Interval	(2-Sided) 90%; 43.50 to 67.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Treatment 3: 2 x 6 mg A-capsule Fed, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 3
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	200.23
	Confidence Interval	(2-Sided) 90%; 160.15 to 250.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Treatment 4: 2 x 6 mg B-capsule Fasted, Treatment 5: 2 x 6 mg B-capsule Fed
	Comments	Pairwise comparison: Treatment 5/Treatment 4
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	73.76
	Confidence Interval	(2-Sided) 90%; 59.30 to 91.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	AUC From Time 0 to 24 Hours Post Dose (AUC0-24) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Pre-dose and up to 24-hours Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	132.6 (48.40)	138.5 (39.67)	54.85 (80.02)	102.9 (54.45)	110.6 (47.83)

5. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Median (Full Range) [Hour]	4.98	4.98	5.00	4.00	7.98

6. Secondary Outcome

Title	Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Mean (Standard Deviation) [Hour]	14.02 (4.732)	13.61 (5.748)	13.42 (5.549)	14.36 (5.477)	12.40 (5.038)

7. Secondary Outcome

Title	Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Mean (Standard Deviation) [Litre/hour]	77.86 (42.15)	75.43 (25.71)	160.5 (86.96)	86.26 (32.22)	87.10 (41.78)

8. Secondary Outcome

Title	Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Mean (Standard Deviation) [Hour]	16.98 (4.006)	15.52 (5.843)	17.43 (4.974)	16.61 (6.049)	18.28 (4.841)

9. Secondary Outcome

Title	Time of Last Quantifiable Plasma Concentration (Tlast) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Median (Full Range) [Hour]	71.65	48.47	47.97	48.03	48.03

10. Secondary Outcome

Title	Volume of Distribution at Steady State (Intravenous Dosing) (Vss/F) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Mean (Standard Deviation) [Litre]	1275 (612.8)	1190 (586.4)	2756 (1577)	1472 (855.9)	1645 (1157)

11. Secondary Outcome

Title	Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) for the Analysis of PK Parameter
Description	To examine the PK profiles of verinurad when administered as the 3 different capsule formulations under fasted conditions.
Time Frame	Day 1: Pre-dose and up to 72-hour Post-dose

Outcome Measure Data

Analysis Population Description

The PK analysis set consisted of all subjects in the safety analysis set for whom at least 1 of the primary PK parameters could be calculated, and who had no major protocol deviations thought to impact on the analysis of the PK data.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Mean (Standard Deviation) [Litre]	1529 (953.1)	1490 (779.9)	3120 (2066)	1810 (1120)	1719 (1608)

12. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	To assess AEs as variable of safety and tolerability of single doses of verinurad in healthy participants.
Time Frame	From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose)

Outcome Measure Data

Analysis Population Description

All subjects who received at least 1 dose of verinurad (any formulation) were included in the safety analysis for the study.

Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted	Treatment 2: 2 x 6 mg A-capsule Fasted	Treatment 3: 2 x 6 mg A-capsule Fed	Treatment 4: 2 x 6 mg B-capsule Fasted	Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.	During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
Measure Participants	25	25	25	25	25
Any treatment emergent adverse event (TEAE)	5 20%	6 NaN	2 NaN	4 NaN	3 NaN
Related TEAEs	2 8%	0 NaN	1 NaN	3 NaN	0 NaN
Any serious TEAE (including death)	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
Any TEAE leading to discontinuation of IMP	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
Any TEAE leading to withdrawal from study	0 0%	0 NaN	0 NaN	0 NaN	0 NaN

Adverse Events

Time Frame	From screening (Day -28 to Day -2) till follow-up visit (7 to 14 days post-final dose)
Arm/Group Title	Treatment 1: 1 x 12 mg ER8 Capsule Fasted		Treatment 2: 2 x 6 mg A-capsule Fasted		Treatment 3: 2 x 6 mg A-capsule Fed		Treatment 4: 2 x 6 mg B-capsule Fasted		Treatment 5: 2 x 6 mg B-capsule Fed
Arm/Group Description	During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.		During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.		During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.		During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.		During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.
All Cause Mortality
	Treatment 1: 1 x 12 mg ER8 Capsule Fasted		Treatment 2: 2 x 6 mg A-capsule Fasted		Treatment 3: 2 x 6 mg A-capsule Fed		Treatment 4: 2 x 6 mg B-capsule Fasted		Treatment 5: 2 x 6 mg B-capsule Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)		0/25 (0%)		0/25 (0%)		0/25 (0%)
Serious Adverse Events
	Treatment 1: 1 x 12 mg ER8 Capsule Fasted		Treatment 2: 2 x 6 mg A-capsule Fasted		Treatment 3: 2 x 6 mg A-capsule Fed		Treatment 4: 2 x 6 mg B-capsule Fasted		Treatment 5: 2 x 6 mg B-capsule Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)		0/25 (0%)		0/25 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Treatment 1: 1 x 12 mg ER8 Capsule Fasted		Treatment 2: 2 x 6 mg A-capsule Fasted		Treatment 3: 2 x 6 mg A-capsule Fed		Treatment 4: 2 x 6 mg B-capsule Fasted		Treatment 5: 2 x 6 mg B-capsule Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/25 (20%)		6/25 (24%)		2/25 (8%)		4/25 (16%)		3/25 (12%)
Gastrointestinal disorders
Abdominal discomfort	0/25 (0%)	0	0/25 (0%)	0	0/25 (0%)	0	0/25 (0%)	0	1/25 (4%)	1
Abdominal pain	0/25 (0%)	0	0/25 (0%)	0	1/25 (4%)	1	1/25 (4%)	1	0/25 (0%)	0
Diarrhoea	0/25 (0%)	0	0/25 (0%)	0	1/25 (4%)	1	1/25 (4%)	1	0/25 (0%)	0
General disorders
Catheter site pain	1/25 (4%)	1	1/25 (4%)	1	0/25 (0%)	0	0/25 (0%)	0	0/25 (0%)	0
Catheter site related reaction	0/25 (0%)	0	1/25 (4%)	1	0/25 (0%)	0	1/25 (4%)	1	0/25 (0%)	0
Infections and infestations
Oral herpes	0/25 (0%)	0	1/25 (4%)	1	0/25 (0%)	0	1/25 (4%)	1	0/25 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/25 (8%)	2	1/25 (4%)	1	0/25 (0%)	0	0/25 (0%)	0	0/25 (0%)	0
Nervous system disorders
Headache	1/25 (4%)	1	1/25 (4%)	1	1/25 (4%)	1	1/25 (4%)	1	1/25 (4%)	1
Reproductive system and breast disorders
Dysmenorrhoea	1/25 (4%)	1	0/25 (0%)	0	0/25 (0%)	0	1/25 (4%)	1	0/25 (0%)	0
Respiratory, thoracic and mediastinal disorders
Throat irritation	0/25 (0%)	0	1/25 (4%)	1	0/25 (0%)	0	0/25 (0%)	0	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Rash	0/25 (0%)	0	0/25 (0%)	0	1/25 (4%)	1	0/25 (0%)	0	0/25 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

This confidential document is the property of AstraZeneca AB. No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.