Chronic Kidney DiseasePhase 1NCT03836599

A Study to Assess the Safety and Pharmacokinetics of Verinurad and Allopurinol in Asian and Chinese Subjects

A Phase 1 study testing Verinurad and Allopurinol in people with Chronic Kidney Disease, run by AstraZeneca at 1 site in United States.

Completed

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

Official record

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Trial summary

This is a randomized, placebo controlled, double-blind study with two separate cohorts to assess safety, tolerability and pharmacokinetics of verinurad and allopurinol in healthy subjects. Read more about this study

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 and Allopurinol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 6 participants
Where: 1 siteUnited States
Study dates: 16 Jan 2019to 26 Apr 2019
Phase: Phase 1
Are there results?: None posted in the registry

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.
Applicable only to Cohort 1: Healthy male and female Asian subjects aged 18 to 50 years (inclusive) at the Screening Visit with suitable veins for cannulation or repeated venipuncture. A subject will be considered Asian if the subject and both of the subject's parents are part of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam).
Applicable only to Cohort 2: Healthy male and female Chinese subjects aged 18 to 50 years (inclusive) at the Screening Visit with suitable veins for cannulation or repeated venipuncture. A subject will be considered Chinese if:
Both parents and all grandparents are Chinese, and
Subject was born in China, and
Subject has not lived outside China for more than 10 years.

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Subject has a sUA acid level > 4.0 mg/dL at the Screening Visit. The assessment may be repeated once during the Screening Period.
Females must have a negative pregnancy test at the Screening Visit and Day -7, must not be lactating and must be:
Of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:
Post-menopausal 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 post-menopausal range (FSH levels > 40 IU/mL).
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.

Who cannot join

Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at the Screening Visit as judged by the Investigator including:
Alanine aminotransferase (ALT) >1.5 x upper limit of normal (ULN);
Aspartate aminotransferase (AST) >1.5 x ULN;
Bilirubin (total) > 1.5 x ULN; and
Gamma glutamyl transpeptidase (GGT) >1.5 x ULN. If any these tests are out-of-range the test can be repeated once at the Screening Visit at the discretion of the Investigator.
Known carrier of the Human Leukocyte Antigen-B (HLA-B) *58:01 allele.

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Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
Suspected or known Gilbert's syndrome.
Current smokers or those who have smoked or used nicotine products (including e-cigarettes within the previous 3 months).
Positive screen for drugs of abuse, cotinine (nicotine) or alcohol at the Screening Visit or on Day -7.
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 investigational product or within 5 half-lives (whichever is longer). The use of hormonal contraception therapy and hormonal replacement therapy for females are permitted.
Has received another new chemical or biological entity (defined as a compound which has not been approved for marketing in the US) within 30 days or within 5 half-lives (whichever is longer) of the first administration of investigational drug in this study.
Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
Subjects who are vegans or have medical dietary restrictions.

Trial locations and contacts

1 site in 1 country.

United States1 site

Research Site
Glendale, California, 91206

Other trials in United States

About this study

Official title: A Phase I Randomized Double-blind Placebo-controlled Study With 2 Separate Cohorts to Assess the Safety, Tolerability and Pharmacokinetics of Verinurad and Allopurinol in Healthy Asian and Chinese Subjects

This is a randomized, placebo controlled, double-blind study with two separate cohorts to assess safety, tolerability and pharmacokinetics of verinurad and allopurinol in healthy subjects.

In cohort 1, twelve Asian subjects will be treated with allopurinol 300mg for 7 days followed by either allopurinol 300mg and verinurad 24mg or matching placebo for 7 days.

In Cohort 2, nine Chinese subjects will be treated with allopurinol 300mg for 7 days followed by allopurinol 300mg and verinurad 12mg administered on 7 out of 8 days.

Read the detailed description

This is a Phase I study with 2 parallel cohorts which will be performed at a single study center.

Cohort-1 will comprise of 12 healthy Asian participants, and will follow a randomized, double-blind, placebo-controlled design. The number of Chinese participants included in Cohort 1 must be less than 50% of the total number of participants enrolled into the cohort. Nine participants will be randomized to receive 24 mg verinurad and 300 mg allopurinol once daily for 7 days and 3 participants will be randomized to receive matching placebos once daily for 7 days. Cohort 1 participants will undergo a Screening Period of a maximum of 28 days followed by a 7-day Run-in Period during which participants will receive 300 mg allopurinol or matching placebo once daily. Participants will then be randomized before the start of the Run-in Period. The Run-in Period is intended to decrease the risk of skin toxicity of allopurinol. Participants will be admitted to the clinical unit 2-days before the treatment period, during which they will receive once daily doses of 24 mg verinurad and 300 mg allopurinol or matching placebos. Participants will be discharged from the clinical unit on Day 8, but will return for a Follow-up Visit within 7 to 14 days.

Cohort-2 will comprise of 9 healthy Chinese participants and will follow an open-label design. All 9 Chinese participants will receive 12 mg verinurad and 300 mg allopurinol on Day 1 and Day 3 to Day 9. For Cohort-2, participants will undergo a Screening Period of a maximum of 28 days followed by a 7-day Run-in Period during which participants will receive 300 mg allopurinol once daily. Participants will be admitted to the Clinical Unit on Day -2, and will receive a single dose of 12 mg verinurad and 300 mg allopurinol on Day 1. No dosing will be done on Day 2. Participants will continue dosing on Day 3 and will be dosed once daily until Day 9. Participants will be discharged from the Clinical Unit on Day 10, but will return for a Follow-up Visit within 7 to 14 days.

Conditions: Chronic Kidney Disease
Being tested: Verinurad, Allopurinol, Placebo
Keywords: Uric acid transporter 1 (URAT1) Inhibitor, Xantine oxidoreductase inhibitor, Pharmacokinetics, Verinurad, Allopurinol
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.

VerinuradDrug
Participants will receive verinurad 24 mg in cohort 1 and 12 mg in cohort 2 once daily.
AllopurinolDrug
Participants will receive allopurinol 300 mg once daily.
PlaceboDrug
During Run-in Period, participants in cohort 1 will receive placebo matching allopurinol capsule once daily from Day -7 to Day -1. During treatment period, participants in cohort 1 will receive placebo matching allopurinol capsule and placebo matching verinurad capsule once daily from Day 1 to Day 7.

Study groups in NCT03836599
Study group	Role	What they receive
24 mg Verinurad+300 mg allopurinol	Experimental	During Run-in Period, participants will be dosed with 300 mg of allopurinol from Day -7 to Day -1. During the Treatment Period, participants will be administered 24 mg verinurad with 300 mg allopurinol once daily on Days 1 to 7. Receives: Drug: Verinurad; Drug: Allopurinol
12 mg Verinurad+300 mg allopurinol	Experimental	During Run-in Period, participants will be dosed with 300 mg of allopurinol once daily from Day -7 to Day -1. During Treatment Period, participants will receive a single dose of 12 mg verinurad and 300 mg allopurinol on Day 1. No dosing will be done on Day 2. Participants will continue dosing on Day 3 and will be dosed once daily until Day 9. Receives: Drug: Verinurad; Drug: Allopurinol
Placebo	Placebo comparator	During Run-in Period, participants in cohort 1 will receive placebo matching allopurinol capsule once daily from Day -7 to Day -1. During treatment period, participants in cohort 1 will receive placebo matching allopurinol capsule and placebo matching verinurad capsule once daily from Day 1 to Day 7. Receives: Drug: Placebo

What is being measured

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

Number of participants with adverse events
To assess the safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Follow-up visit/Early discontinuation visit (EDV) (7-14 Days Post-last PK Sample)
Number of participants with abnormal findings in electrocardiography (ECG)
To assess abnormal resting digital 12-lead electrocardiograms as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
Number of participants with abnormal pulse rate
To assess abnormal pulse rate as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
Number of participants with abnormal hematology
To assess white blood cell count (WBC), red blood cell count (RBC), neutrophils absolute count, lymphocytes absolute count, monocytes absolute count, eosinophils absolute count, basophils absolute count, platelets, and reticulocytes absolute count as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
Number of participants with abnormal blood pressure (systolic and diastolic)
To assess abnormal blood pressure (systolic and diastolic) as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)]
Number of participants with abnormal physical examination
To assess safety and tolerability by assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK sample)]
Number of participants with abnormal electrolytes
To assess serum level of sodium, potassium, calcium (total), and phosphate as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK smaple)]
Number of participants with abnormal hemoglobin (Hb)
To assess Hb as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
Number of participants with abnormal hematocrit
To assess hematocrit as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
Number of participants with abnormal Mean corpuscular volume (MCV)
To assess MCV as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
Number of participants with abnormal mean corpuscular hemoglobin (MCH)
To assess MCH as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
Number of participants with abnormal mean corpuscular hemoglobin concentration (MCHC)
To assess MCHC as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Measured: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
Number of participants with abnormal clinical chemistry
To assess the safety and tolerability profile of verinurad and allopurinol treatment in terms of the number of participants with abnormal clinical chemistry values. The laboratory variables to be measured are: bilirubin, creatinine, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cystatin C, gamma glutamyl transpeptidase, urea and uric acid.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
Number of participants with abnormal urinalysis.
To assess the safety and tolerability profile of verinurad and allopurinol treatment in terms of the number of participants with abnormal urinalysis values. The laboratory variables to be measured are: protein, glucose, blood, uric acid, pH, sodium, creatinine, and cystatin C.
Measured: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)

Secondary outcomes (10)

Area under plasma concentration-time curve from zero to infinity (AUC), AUC(0-t), AUC(0-24), and AUCτ
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 1, Days 3 to 6, Day 7 (cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2).
Observed concentration and percentage change from baseline in serum uric acid
To evaluate serum uric acid of verinurad and allopurinol treatment in terms of the number of participants with observed concentration and percentage change from baseline in serum uric acid.
Measured: On Day -1: -24, -21, -18, and -12 hours prior to dosing on Day 1. On Days 1, 7 and 9 (Pre-dose, 3, 6, 12, and 24 hours post-dose).
Observed concentration and percentage change from baseline in urine uric acid
To evaluate urine uric acid of verinurad and allopurinol treatment in terms of the number of participants with observed concentration and percentage change from baseline in urine uric acid.
Measured: On Day -1: baseline collection of urine: -24 to -22 h, -22 h to -20 h, -18 h to -16 h, -16 h to - 12 h and -12 h to 0 h prior to dosing on Day 1, on Days 1, 7 and 9 (0-2 h, 2-4 h, 4-6 h, 6-8 h, 8-12 h, and 12-24 h post-dose).
Maximum observed plasma concentration (Cmax) and Minimum observed plasma concentration (Cmin)
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 1, Days 3 to 6, Day 7(cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Time to reach maximum observed plasma concentration (tmax) and Time of last measurable concentration (tlast)
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 1, Days 3 to 6, Day 7 (cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2).
Apparent total body clearance of drug from plasma after extravascular administration across the dosing interval (CL/F)
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 1, Days 3 to 6, Day 7(cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 1, Days 3 to 6, Day 7(cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Apparent volume of distribution based on the terminal phase (Vz/F) and Apparent volume of distribution during the terminal phase after extravascular administration (Vss/F)
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 1, Days 3 to 6, Day 7 (cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Mean residence time (MRT)
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 1
Accumulation ratio for Cmax and AUCτ
To evaluate the pharmacokinetics of verinurad, allopurinol and oxypurinol in healthy Asian and Chinese participants.
Measured: On Day 7 (Cohort 1) or Day 9 (Cohort 2)

Timeline

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

16 Jan 201926 Apr 2019

First posted11 Feb 2019
Study start16 Jan 2019
Primary completion26 Apr 2019
Study completion26 Apr 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
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: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03836599
Sponsor's protocol ID: D5495C00006
Status last verified: May 2019
First submitted: 21 Dec 2018
Last updated: 13 May 2019
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

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 13 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Randomized Double-blind Placebo-controlled Study With 2 Separate Cohorts to Assess the Safety, Tolerability and Pharmacokinetics of Verinurad and Allopurinol in Healthy Asian and Chinese Subjects
ClinicalTrials.gov ID: NCT03836599
Acronym / sponsor ID: D5495C00006
Conditions: Chronic Kidney Disease
Keywords: Uric acid transporter 1 (URAT1) Inhibitor, Xantine oxidoreductase inhibitor, Pharmacokinetics, Verinurad, Allopurinol
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 6 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Parexel
Study start: 16 Jan 2019 (actual)
Primary completion: 26 Apr 2019 (actual)
Study completion: 26 Apr 2019 (actual)
First posted: 11 Feb 2019 (actual)
Results: Not posted in the source record

Clinical summary

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

This is a randomized, placebo controlled, double-blind study with two separate cohorts to assess safety, tolerability and pharmacokinetics of verinurad and allopurinol in healthy subjects.

In cohort 1, twelve Asian subjects will be treated with allopurinol 300mg for 7 days followed by either allopurinol 300mg and verinurad 24mg or matching placebo for 7 days.

In Cohort 2, nine Chinese subjects will be treated with allopurinol 300mg for 7 days followed by allopurinol 300mg and verinurad 12mg administered on 7 out of 8 days.

Detailed description

This is a Phase I study with 2 parallel cohorts which will be performed at a single study center.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
24 mg Verinurad+300 mg allopurinol	Experimental	Drug: Verinurad, Drug: AllopurinolDuring Run-in Period, participants will be dosed with 300 mg of allopurinol from Day -7 to Day -1. During the Treatment Period, participants will be administered 24 mg verinurad with 300 mg allopurinol once daily on Days 1 to 7.
12 mg Verinurad+300 mg allopurinol	Experimental	Drug: Verinurad, Drug: AllopurinolDuring Run-in Period, participants will be dosed with 300 mg of allopurinol once daily from Day -7 to Day -1. During Treatment Period, participants will receive a single dose of 12 mg verinurad and 300 mg allopurinol on Day 1. No dosing will be done on Day 2. Participants will continue dosing on Day 3 and will be dosed once daily until Day 9.
Placebo	Placebo comparator	Drug: PlaceboDuring Run-in Period, participants in cohort 1 will receive placebo matching allopurinol capsule once daily from Day -7 to Day -1. During treatment period, participants in cohort 1 will receive placebo matching allopurinol capsule and placebo matching verinurad capsule once daily from Day 1 to Day 7.

Who may qualify

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

Key inclusion criteria (12 listed)

Provision of signed and dated, written informed consent prior to any study specific procedures.
Applicable only to Cohort 1: Healthy male and female Asian subjects aged 18 to 50 years (inclusive) at the Screening Visit with suitable veins for cannulation or repeated venipuncture. A subject will be considered Asian if the subject and both of the subject's parents are part of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam).
Applicable only to Cohort 2: Healthy male and female Chinese subjects aged 18 to 50 years (inclusive) at the Screening Visit with suitable veins for cannulation or repeated venipuncture. A subject will be considered Chinese if:
Subject has a sUA acid level > 4.0 mg/dL at the Screening Visit. The assessment may be repeated once during the Screening Period.
Females must have a negative pregnancy test at the Screening Visit and Day -7, must not be lactating and must be:

Key exclusion criteria (14 listed)

Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at the Screening Visit as judged by the Investigator including:
Known carrier of the Human Leukocyte Antigen-B (HLA-B) *58:01 allele.
Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
Suspected or known Gilbert's syndrome.
Current smokers or those who have smoked or used nicotine products (including e-cigarettes within the previous 3 months).

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
VerinuradParticipants will receive verinurad 24 mg in cohort 1 and 12 mg in cohort 2 once daily.	Drug	12 mg Verinurad+300 mg allopurinol, 24 mg Verinurad+300 mg allopurinol
AllopurinolParticipants will receive allopurinol 300 mg once daily.	Drug	12 mg Verinurad+300 mg allopurinol, 24 mg Verinurad+300 mg allopurinol
PlaceboDuring Run-in Period, participants in cohort 1 will receive placebo matching allopurinol capsule once daily from Day -7 to Day -1. During treatment period, participants in cohort 1 will receive placebo matching allopurinol capsule and placebo matching verinurad capsule once daily from Day 1 to Day 7.	Drug	Placebo

Primary outcome

Number of participants with adverse events
Time frame: From screening up to Follow-up visit/Early discontinuation visit (EDV) (7-14 Days Post-last PK Sample)
To assess the safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal findings in electrocardiography (ECG)
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
To assess abnormal resting digital 12-lead electrocardiograms as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal pulse rate
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
To assess abnormal pulse rate as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal hematology
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
To assess white blood cell count (WBC), red blood cell count (RBC), neutrophils absolute count, lymphocytes absolute count, monocytes absolute count, eosinophils absolute count, basophils absolute count, platelets, and reticulocytes absolute count as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal blood pressure (systolic and diastolic)
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)]
To assess abnormal blood pressure (systolic and diastolic) as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal physical examination
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK sample)]
To assess safety and tolerability by assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.
Number of participants with abnormal electrolytes
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK smaple)]
To assess serum level of sodium, potassium, calcium (total), and phosphate as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal hemoglobin (Hb)
Time frame: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
To assess Hb as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal hematocrit
Time frame: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
To assess hematocrit as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal Mean corpuscular volume (MCV)
Time frame: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
To assess MCV as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal mean corpuscular hemoglobin (MCH)
Time frame: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
To assess MCH as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal mean corpuscular hemoglobin concentration (MCHC)
Time frame: From screening up to Followup visit/EDV (7-14 Days Postlast PK Sample)
To assess MCHC as a variable of safety and tolerability of verinurad and allopurinol in healthy Asian and Chinese participants.
Number of participants with abnormal clinical chemistry
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
To assess the safety and tolerability profile of verinurad and allopurinol treatment in terms of the number of participants with abnormal clinical chemistry values. The laboratory variables to be measured are: bilirubin, creatinine, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), cystatin C, gamma glutamyl transpeptidase, urea and uric acid.
Number of participants with abnormal urinalysis.
Time frame: From screening up to Follow-up visit/EDV (7-14 Days Post-last PK Sample)
To assess the safety and tolerability profile of verinurad and allopurinol treatment in terms of the number of participants with abnormal urinalysis values. The laboratory variables to be measured are: protein, glucose, blood, uric acid, pH, sodium, creatinine, and cystatin C.

10 secondary outcomes

Area under plasma concentration-time curve from zero to infinity (AUC), AUC(0-t), AUC(0-24), and AUCτ
Time frame: On Day 1, Days 3 to 6, Day 7 (cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2).
Observed concentration and percentage change from baseline in serum uric acid
Time frame: On Day -1: -24, -21, -18, and -12 hours prior to dosing on Day 1. On Days 1, 7 and 9 (Pre-dose, 3, 6, 12, and 24 hours post-dose).
Observed concentration and percentage change from baseline in urine uric acid
Time frame: On Day -1: baseline collection of urine: -24 to -22 h, -22 h to -20 h, -18 h to -16 h, -16 h to - 12 h and -12 h to 0 h prior to dosing on Day 1, on Days 1, 7 and 9 (0-2 h, 2-4 h, 4-6 h, 6-8 h, 8-12 h, and 12-24 h post-dose).
Maximum observed plasma concentration (Cmax) and Minimum observed plasma concentration (Cmin)
Time frame: On Day 1, Days 3 to 6, Day 7(cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Time to reach maximum observed plasma concentration (tmax) and Time of last measurable concentration (tlast)
Time frame: On Day 1, Days 3 to 6, Day 7 (cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2).
Apparent total body clearance of drug from plasma after extravascular administration across the dosing interval (CL/F)
Time frame: On Day 1, Days 3 to 6, Day 7(cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Time frame: On Day 1, Days 3 to 6, Day 7(cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Apparent volume of distribution based on the terminal phase (Vz/F) and Apparent volume of distribution during the terminal phase after extravascular administration (Vss/F)
Time frame: On Day 1, Days 3 to 6, Day 7 (cohort 1). On Day 1, Day 2, Days 3 to 8, and Day 9 (Cohort 2)
Mean residence time (MRT)
Time frame: On Day 1
Accumulation ratio for Cmax and AUCτ
Time frame: On Day 7 (Cohort 1) or Day 9 (Cohort 2)

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2019.
Individual participant dataSharing planned: Undecided

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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.

David Han, MD principal investigator

Parexel

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Verinurad and Allopurinol in people with Chronic Kidney Disease, run by AstraZeneca at 1 site in United States.

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

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 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 13 May 2019. 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 United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

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

What does this phase mean?

Phase 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of participants with adverse events (time frame: From screening up to Follow-up visit/Early discontinuation visit (EDV) (7-14 Days Post-last PK Sample)). The study lists 14 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 NCT03836599.

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 13 May 2019.