Chronic Kidney DiseasePhase 1NCT04550234

A Study in Healthy Subjects to Assess Drug Availability of 4 Different Formulations of Verinurad and Allopurinol

A Phase 1 study testing Verinurad prolonged release HPMC capsule, Allopurinol Tablet and Verinurad/Allopurinol FDC Capsule in people with Chronic Kidney Disease, run by AstraZeneca at 1 site in Germany.

Completed

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

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Chronic Kidney Disease
What is being tested?: Verinurad prolonged release HPMC capsule, Allopurinol Tablet and Verinurad/Allopurinol FDC Capsule
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 1 siteGermany
Study dates: 13 Apr 2021to 15 Jul 2021
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Provision of signed and dated, written informed consent prior to any study specific procedures.
Healthy male and female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venepuncture.
Have a body mass index between 18 and 30 kg/m^2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).
Females must have a negative pregnancy test at screening and on admission to the unit and must be:
not pregnant or currently lactating or breastfeeding.
of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria: (i) postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the postmenopausal range (FSH levels > 40 IU/mL).

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documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
OR if of childbearing potential must be willing to use an acceptable method of contraception to avoid pregnancy for the entire study period.
Must be able to swallow multiple capsules and tablets.

Who cannot join

History of gout or any clinically significant disease 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.
Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of verinurad.
History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results as judged by the Investigator at screening and first admission, including:
Alanine aminotransferase > 1.5 x upper limit of normal (ULN),
Aspartate aminotransferase > 1.5 x ULN,

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Bilirubin (total) > 1.5 x ULN,
Gamma glutamyl transpeptidase > 1.5 x ULN.
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:
Pulse (resting, supine) < 50 beats per minute (bpm) or > 90 bpm,
Systolic blood pressure (BP) < 90 mmHg or > 140 mmHg and/or diastolic BP < 50 mmHg or > 90 mmHg sustained for > 10 minutes while resting in a supine position.
Any clinically significant abnormalities on 12 lead electrocardiogram (ECG) at the Screening Visit, including, but not limited to any of the following:
QTcF > 450 ms or < 340 ms or family history of long QT syndrome,
Any significant arrhythmia
Conduction abnormalities
Clinically significant PR (PQ) interval prolongation (> 240 ms); intermittent second or third degree AV block, or AV dissociation
Complete bundle branch block and/or QRS duration > 120 ms.
Any positive result at the Screening Visit for serum Hepatitis B surface antigen or Anti Hepatitis B core antibody, hepatitis virus C antibody, and human immunodeficiency virus antibody.
Suspicion or known Gilbert's and/or Lesch Nyhan syndrome.
Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI.
Has received another new chemical or biological entity within 30 days or at least 5 half lives of the first administration of verinurad in this study.
Subjects who have previously received verinurad.
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.
Subjects who are pregnant, lactating or planning to become pregnant.
Hypersensitivity to verinurad, allopurinol or any drug with a similar chemical structure/class to verinurad and/or allopurinol.
Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening.
Excessive intake of caffeine containing drinks or food as judged by the PI.
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.
Use of drugs with enzyme inducing properties within 3 weeks prior to the first administration of verinurad.
Use of any prescribed or non prescribed medication including antacids, analgesics, herbal remedies, megadose vitamins and minerals during the 2 weeks prior to the first administration of verinurad or longer if the medication has a long half life.
Any AstraZeneca, Parexel or study site employee or their close relatives.
Subjects who cannot communicate reliably with the PI and/or is not able to read, speak and understand the German language.
Judgment by the PI that the subject 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.
Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
Subjects with any special dietary restrictions such as subjects that are lactose intolerant or are vegetarians/vegans.
Subject is a carrier of the HLA B*58:01 allele.
Subject has a positive test result for severe acute respiratory syndrome corona virus (SARS-CoV-2) RT-PCR before randomisation.
Subject has clinical signs and symptoms consistent with Coronavirus disease 2019 (COVID-19), eg, fever, dry cough, dyspnoea, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
History of severe COVID-19 (hospitalisation, extracorporeal membrane oxygenation, mechanically ventilated).
Subjects who are regularly exposed to COVID-19 as part of their daily life.
Subjects who have had or are planning to have the COVID-19 vaccination within 4 weeks prior to screening or at any time during the study.

Trial locations and contacts

1 site in 1 country.

Germany1 site

Research Site
Berlin, 14050

Other trials in Germany

About this study

Official title: A Randomised, Single Dose, 5-period, 5-treatment, Crossover Study to Assess the Relative Bioavailability of 4 Different Formulations of Verinurad and Allopurinol in Healthy Subjects

This study is a single centre, randomised, open-label, single-dose, 5-period, 5-treatment, crossover study in healthy male and female subjects. This study is intended to assess the relative bioavailability between the fixed dose combination (FDC, i.e. verinurad/allopurinol FDC capsule 12/300 mg) and free combination formulations of verinurad (i.e. verinurad prolonged release Hydroxypropyl methylcellulose [HPMC] capsule 12 mg) and allopurinol (i.e. allopurinol table 300 mg) in fasted and fed conditions. The study will also assess the relative bioavailability between a formulation only containing verinurad (i.e. verinurad prolonged release gelatin capsule 12 mg) and the FDC capsule.

Read the detailed description

The study comprises of:

A Screening Period of maximum 28 days;
Five treatment periods during which subjects will be resident from the morning of Day -2 until at least 72 hours after dosing in Treatment Period 5; discharged on the morning of Day 4 of Treatment Period 5; and
A Follow-up Visit 7 to 14 days after the last dosing.

Each subject will receive 5 single dose treatments of verinurad and allopurinol or verinurad alone and subject will be involved in the study for 52 to 59 days.

Conditions: Chronic Kidney Disease
Being tested: Verinurad prolonged release HPMC capsule, Allopurinol Tablet, Verinurad/Allopurinol FDC Capsule, Verinurad prolonged release gelatin Capsule
Keywords: 3-period, Crossover, URAT1 inhibitor, Xanthine oxidase inhibitor
Medical subject headings: Renal Insufficiency, Chronic

What participants receive

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

Verinurad prolonged release HPMC capsuleDrug
Randomized subjects will receive oral dose of verinurad HPMC capsule.
Allopurinol TabletDrug
Randomized subjects will receive oral dose of allopurinol tablet.
Verinurad/Allopurinol FDC CapsuleDrug
Randomized subjects will receive oral dose of Verinurad/Allopurinol FDC capsule.
Verinurad prolonged release gelatin CapsuleDrug
Randomized subjects will receive oral dose of Verinurad gelatin capsule.

Study groups in NCT04550234
Study group	Role	What they receive
Treatment 1	Experimental	Subjects will receive verinurad prolonged release HPMC capsule and allopurinol tablet in fasted state on Day 1. Receives: Drug: Verinurad prolonged release HPMC capsule; Drug: Allopurinol Tablet
Treatment 2	Experimental	Subjects will receive verinurad/allopurinol FDC capsule in fasted state on Day 1. Receives: Drug: Verinurad/Allopurinol FDC Capsule
Treatment 3	Experimental	Subjects will receive verinurad/allopurinol FDC capsule in fed state on Day 1. Receives: Drug: Verinurad/Allopurinol FDC Capsule
Treatment 4	Experimental	Subjects will receive verinurad prolonged release HPMC capsule and allopurinol tablet in fed state on Day 1. Receives: Drug: Verinurad prolonged release HPMC capsule; Drug: Allopurinol Tablet
Treatment 5	Experimental	Subjects will receive verinurad prolonged release gelatin capsule in fasted state on Day 1. Receives: Drug: Verinurad prolonged release gelatin Capsule

What is being measured

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

AUCinf: Area Under Plasma Concentration-time Curve From 0 to Infinity in Fasted Condition
The AUCinf of verinurad, allopurinol and oxypurinol were assessed in fasted state as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
AUClast: Area Under Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration in Fasted Condition
The AUClast of verinurad, allopurinol and oxypurinol were assessed in fasted condition as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Cmax: Maximum Observed Plasma Drug Concentration in Fasted State
The Cmax of verinurad, allopurinol and oxypurinol were assessed in fasted state as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period

Secondary outcomes (14)

Cmax: Maximum Observed Plasma Drug Concentration
The Cmax of verinurad, allopurinol and oxypurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
AUCinf: Area Under Plasma Concentration-time Curve From 0 to Infinity
The AUCinf of verinurad, allopurinol and oxypurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
AUClast: Area Under Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration
The AUClast of verinurad, allopurinol and oxypurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Tmax: Time to Reach Maximum Observed Plasma Concentration Following Drug Administration
The tmax of verinurad, allopurinol and oxypurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Tlag: Time Delay Between Drug Administration and First Observed Concentration in Plasma
The tlag of verinurad, allopurinol and oxypurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
t½λz: Half-life Associated With Terminal Slope (λz) of Semi-logarithmic Concentration-time Curve
The t½λz of verinurad, allopurinol and oxypurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
λz: Terminal Elimination Rate Constant
The λz of verinurad, allopurinol and oxypurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
CL/F: Apparent Total Body Clearance of Drug Clearance of Drug From Plasma After Extravascular Administration
The CL/F of verinurad and allopurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
MRTinf: Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity
The MRTinf of verinurad and allopurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Vz/F: Apparent Volume of Distribution During Terminal Phase After Extravascular Administration
The Vz/F of verinurad and allopurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Vss/F: Apparent Volume of Distribution at Steady State Following Extravascular Administration
The Vss/F of verinurad and allopurinol were assessed as PK parameters
Measured: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Emax, CB: Maximum Percentage Change From Baseline (CB)
The Emax, CB in serum uric acid (sUA) concentration (time-matched, Day -1) was assessed as PD parameter.
Measured: Day -1, Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
tEmax, CB: Time of Maximum Percentage CB Change From Baseline (CB)
The tEmax, CB in serum uric acid (sUA) concentration (time-matched, Day -1) was assessed as PD parameter.
Measured: Day -1, Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events
The safety of single doses of verinurad and allopurinol were assessed
Measured: From screening (Day -28 to -3) until follow-up visit (7 to 14 days post final dose) (approximately 52 to 59 days)

Timeline

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

13 Apr 202115 Jul 2021

First posted16 Sep 2020
Study start13 Apr 2021
Primary completion15 Jul 2021
Study completion15 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04550234
Sponsor's protocol ID: D5495C00014
Status last verified: Jun 2022
First submitted: 9 Sep 2020
Last updated: 10 May 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the requests portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Single Dose, 5-period, 5-treatment, Crossover Study to Assess the Relative Bioavailability of 4 Different Formulations of Verinurad and Allopurinol in Healthy Subjects
ClinicalTrials.gov ID: NCT04550234
Acronym / sponsor ID: D5495C00014
Conditions: Chronic Kidney Disease
Keywords: 3-period, Crossover, URAT1 inhibitor, Xanthine oxidase inhibitor
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 13 Apr 2021 (actual)
Primary completion: 15 Jul 2021 (actual)
Study completion: 15 Jul 2021 (actual)
First posted: 16 Sep 2020 (actual)
Results: Posted 10 May 2023

Clinical summary

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

Detailed description

The study comprises of:

A Screening Period of maximum 28 days;
Five treatment periods during which subjects will be resident from the morning of Day -2 until at least 72 hours after dosing in Treatment Period 5; discharged on the morning of Day 4 of Treatment Period 5; and
A Follow-up Visit 7 to 14 days after the last dosing.

Each subject will receive 5 single dose treatments of verinurad and allopurinol or verinurad alone and subject will be involved in the study for 52 to 59 days.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Treatment 1	Experimental	Drug: Verinurad prolonged release HPMC capsule, Drug: Allopurinol TabletSubjects will receive verinurad prolonged release HPMC capsule and allopurinol tablet in fasted state on Day 1.
Treatment 2	Experimental	Drug: Verinurad/Allopurinol FDC CapsuleSubjects will receive verinurad/allopurinol FDC capsule in fasted state on Day 1.
Treatment 3	Experimental	Drug: Verinurad/Allopurinol FDC CapsuleSubjects will receive verinurad/allopurinol FDC capsule in fed state on Day 1.
Treatment 4	Experimental	Drug: Verinurad prolonged release HPMC capsule, Drug: Allopurinol TabletSubjects will receive verinurad prolonged release HPMC capsule and allopurinol tablet in fed state on Day 1.
Treatment 5	Experimental	Drug: Verinurad prolonged release gelatin CapsuleSubjects will receive verinurad prolonged release gelatin capsule in fasted state on Day 1.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Provision of signed and dated, written informed consent prior to any study specific procedures.
Healthy male and female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venepuncture.
Have a body mass index between 18 and 30 kg/m^2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive).
Females must have a negative pregnancy test at screening and on admission to the unit and must be:
Must be able to swallow multiple capsules and tablets.

Key exclusion criteria (41 listed)

History of gout or any clinically significant disease 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.
Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of verinurad.
History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results as judged by the Investigator at screening and first admission, including:
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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Verinurad prolonged release HPMC capsuleRandomized subjects will receive oral dose of verinurad HPMC capsule.	Drug	Treatment 1, Treatment 4
Allopurinol TabletRandomized subjects will receive oral dose of allopurinol tablet.	Drug	Treatment 1, Treatment 4
Verinurad/Allopurinol FDC CapsuleRandomized subjects will receive oral dose of Verinurad/Allopurinol FDC capsule.	Drug	Treatment 2, Treatment 3
Verinurad prolonged release gelatin CapsuleRandomized subjects will receive oral dose of Verinurad gelatin capsule.	Drug	Treatment 5

Primary outcome

AUCinf: Area Under Plasma Concentration-time Curve From 0 to Infinity in Fasted Condition
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
The AUCinf of verinurad, allopurinol and oxypurinol were assessed in fasted state as PK parameters
AUClast: Area Under Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration in Fasted Condition
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
The AUClast of verinurad, allopurinol and oxypurinol were assessed in fasted condition as PK parameters
Cmax: Maximum Observed Plasma Drug Concentration in Fasted State
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
The Cmax of verinurad, allopurinol and oxypurinol were assessed in fasted state as PK parameters

14 secondary outcomes

Cmax: Maximum Observed Plasma Drug Concentration
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
AUCinf: Area Under Plasma Concentration-time Curve From 0 to Infinity
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
AUClast: Area Under Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Tmax: Time to Reach Maximum Observed Plasma Concentration Following Drug Administration
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Tlag: Time Delay Between Drug Administration and First Observed Concentration in Plasma
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
t½λz: Half-life Associated With Terminal Slope (λz) of Semi-logarithmic Concentration-time Curve
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
λz: Terminal Elimination Rate Constant
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
CL/F: Apparent Total Body Clearance of Drug Clearance of Drug From Plasma After Extravascular Administration
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
MRTinf: Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Vz/F: Apparent Volume of Distribution During Terminal Phase After Extravascular Administration
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Vss/F: Apparent Volume of Distribution at Steady State Following Extravascular Administration
Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Emax, CB: Maximum Percentage Change From Baseline (CB)
Time frame: Day -1, Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
tEmax, CB: Time of Maximum Percentage CB Change From Baseline (CB)
Time frame: Day -1, Day 1, Day 2, Day 3 and Day 4 of each Treatment Period
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events
Time frame: From screening (Day -28 to -3) until follow-up visit (7 to 14 days post final dose) (approximately 52 to 59 days)

Results and safety

Results posted to the registry on 10 May 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Sequence 12345	5	5
Treatment Sequence 23451	5	5
Treatment Sequence 34512	5	5
Treatment Sequence 45123	5	5
Treatment Sequence 51234	5	5

Primary outcome: AUCinf: Area Under Plasma Concentration-time Curve From 0 to Infinity in Fasted Condition

Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period. Geometric mean (Geometric Coefficient of Variation). Unit: hour*nanogram/millilitre

Measure	Treatment 1 n = 25	Treatment 2 n = 25
Verinurad	180.4 (48.87)	195.2 (48.63)
Allopurinol	4486 (37.86)	4332 (46.40)
Oxypurinol	170100 (19.07)	167900 (24.10)

Treatment 1 vs Treatment 2: Geometric mean ratio: 108.25 (90% CI 94.13 to 124.49)
Treatment 1 vs Treatment 2: Geometric mean ratio: 96.57 (90% CI 90.96 to 102.53)
Treatment 1 vs Treatment 2: Geometric mean ratio: 98.75 (90% CI 95.27 to 102.36)

Population analysed: The PK analysis set included all subjects in the safety analysis set who received a verinurad + allopurinol (or verinurad alone for Treatment 5) dose and who had at least one quantifiable post-dose plasma concentration. Here, number analysed in each row signifies the subjects with available data that were analysed for each drug for that outcome measure.

Primary outcome: AUClast: Area Under Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration in Fasted Condition

Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period. Geometric mean (Geometric Coefficient of Variation). Unit: hour*nanogram/milliliter

Measure	Treatment 1 n = 25	Treatment 2 n = 25
Verinurad	169.3 (47.82)	185.0 (49.64)
Allopurinol	4407 (37.98)	4251 (46.91)
Oxypurinol	157100 (16.84)	153100 (21.35)

Treatment 1 vs Treatment 2: Geometric mean ratio: 109.27 (90% CI 94.55 to 126.29)
Treatment 1 vs Treatment 2: Geometric mean ratio: 96.47 (90% CI 90.38 to 102.97)
Treatment 1 vs Treatment 2: Geometric mean ratio: 97.48 (90% CI 94.34 to 100.73)

Primary outcome: Cmax: Maximum Observed Plasma Drug Concentration in Fasted State

Time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram/millilitre

Measure	Treatment 1 n = 25	Treatment 2 n = 25
Verinurad	26.62 (50.71)	34.95 (61.87)
Allopurinol	1526 (37.98)	1471 (42.92)
Oxypurinol	6376 (16.67)	6066 (21.61)

Treatment 1 vs Treatment 2: Geometric mean ratio: 131.28 (90% CI 107.03 to 161.02)
Treatment 1 vs Treatment 2: Geometric mean ratio: 96.39 (90% CI 81.23 to 114.39)
Treatment 1 vs Treatment 2: Geometric mean ratio: 95.15 (90% CI 91.08 to 99.40)

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: From screening (Day -28 to -3) until follow-up visit (7 to 14 days post final dose) (approximately 52 to 59 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment 1	0 of 25 (0%)	8 of 25 (32%)	0 of 25
Treatment 2	0 of 25 (0%)	2 of 25 (8%)	0 of 25
Treatment 3	0 of 25 (0%)	2 of 25 (8%)	0 of 25
Treatment 4	0 of 25 (0%)	6 of 25 (24%)	0 of 25
Treatment 5	0 of 25 (0%)	2 of 25 (8%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
D5495C00014 CSR SynopsisLink provided by the sponsor.
D5495C00014 ProtocolLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the requests portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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Chronic Kidney Diseases

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

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

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUCinf: Area Under Plasma Concentration-time Curve From 0 to Infinity in Fasted Condition (time frame: Day 1, Day 2, Day 3 and Day 4 of each Treatment Period). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04550234.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.