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A Study to Assess the Effect of Verinurad on the Electric Activity of the Heart

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04256629
Recruitment Status : Completed
First Posted : February 5, 2020
Last Update Posted : September 7, 2020
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This study will be conducted to investigate the safety of verinurad in healthy volunteers in combination with allopurinol 300 mg, compared with placebo in particular its effect on electrocardiogram (ECG), with focus on the QT/QTc interval

Condition or disease Intervention/treatment Phase
Healthy Volunteers (Intended Indication: Chronic Kidney Disease) Drug: Verinurad Drug: Placebo Drug: Allopurinol Phase 1

Detailed Description:

This study will be conducted as a single-centre, randomised, placebo-controlled, double-blind, 3-period, crossover study to assess the effect on the QTcF interval of a single oral dose of verinurad 24 mg extended release (ER8) formulation (therapeutic exposure) or verinurad 40 mg immediate release (IR) formulation (supra-therapeutic exposure), each in combination with allopurinol 300 mg, compared to placebo in healthy subjects.

There are 3 study treatments:

  • Treatment A: Verinurad 24 mg ER8 formulation co-administered with 300 mg allopurinol
  • Treatment B: Verinurad 40 mg IR formulation co-administered with 300 mg allopurinol
  • Treatment C: Matched placebos for both verinurad and allopurinol

All subjects will receive a single dose of all 3 treatments (A, B, and C) in a cross-over design with wash-out periods of at least 7 days between each study dose administration.

Subjects will be randomised to the treatment sequence (ABC, BCA, CAB, etc.) using William's Latin square. The treatments will be administered in a double-blind manner after an overnight fast of at least 10 hours.

The study will comprise the following periods (visits):

  • Screening Period of maximum 28 days (Visit 1);
  • Three treatment periods of 3 days each, during which subjects will be resident at the study centre from the morning of the day before administration of the study dose until discharge 2 days after study dose administration (Visits 2 to 4);
  • Wash-out periods of at least 7 days between each study dose administration;
  • Final visit within 7 to 10 days after the last study dose administration (Visit 5).

Each subject will be involved in the study for approximately 53 days and have 5 study visits.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: This study is double-blind with regards to treatment (verinurad and allopurinol or the matching placebos) at each dose level. Placebo will be matched with verinurad and allopurinol for appearance and amount. Subjects randomized to placebo will receive the same volume of oral suspension as subjects on active drug.
Primary Purpose: Treatment
Official Title: Single-Centre, Randomised, Double-Blind, 3-Period Cross-Over Study to Investigate Effects on QTcF Interval of Verinurad ER 24 mg or IR 40 mg in Combination With Allopurinol 300 mg, Compared to Matching Placebos In Healthy Volunteers
Actual Study Start Date : March 3, 2020
Actual Primary Completion Date : August 21, 2020
Actual Study Completion Date : August 21, 2020


Arm Intervention/treatment
Experimental: Treatment ABC
Subjects will receive a single dose of all 3 treatments (A, B, and C) in a crossover design with wash-out periods of at least 7 days between each study dose administration.
Drug: Verinurad
Randomized subjects will receive oral dose of verinurad
Other Names:
  • verinurad ER 24 mg
  • verinurad IR 40 mg

Drug: Placebo
Randomized subjects will receive oral dose of placebo
Other Names:
  • verinurad matching placebo
  • allopurinol matching placebo

Drug: Allopurinol
Randomized subjects will receive oral dose of allpurinol (Treatment A and B)
Other Name: allopurinol 300 mg

Experimental: Treatment BCA
Subjects will receive a single dose of all 3 treatments (B, C, and A) in a crossover design with wash-out periods of at least 7 days between each study dose administration.
Drug: Verinurad
Randomized subjects will receive oral dose of verinurad
Other Names:
  • verinurad ER 24 mg
  • verinurad IR 40 mg

Drug: Placebo
Randomized subjects will receive oral dose of placebo
Other Names:
  • verinurad matching placebo
  • allopurinol matching placebo

Drug: Allopurinol
Randomized subjects will receive oral dose of allpurinol (Treatment A and B)
Other Name: allopurinol 300 mg

Experimental: Treatment CAB
Subjects will receive a single dose of all 3 treatments (C, A, and B) in a crossover design with wash-out periods of at least 7 days between each study dose administration.
Drug: Verinurad
Randomized subjects will receive oral dose of verinurad
Other Names:
  • verinurad ER 24 mg
  • verinurad IR 40 mg

Drug: Placebo
Randomized subjects will receive oral dose of placebo
Other Names:
  • verinurad matching placebo
  • allopurinol matching placebo

Drug: Allopurinol
Randomized subjects will receive oral dose of allpurinol (Treatment A and B)
Other Name: allopurinol 300 mg

Experimental: Treatment ACB
Subjects will receive a single dose of all 3 treatments (A, C, and B) in a crossover design with wash-out periods of at least 7 days between each study dose administration.
Drug: Verinurad
Randomized subjects will receive oral dose of verinurad
Other Names:
  • verinurad ER 24 mg
  • verinurad IR 40 mg

Drug: Placebo
Randomized subjects will receive oral dose of placebo
Other Names:
  • verinurad matching placebo
  • allopurinol matching placebo

Drug: Allopurinol
Randomized subjects will receive oral dose of allpurinol (Treatment A and B)
Other Name: allopurinol 300 mg

Experimental: Treatment BAC
Subjects will receive a single dose of all 3 treatments (B, A, and C) in a crossover design with wash-out periods of at least 7 days between each study dose administration.
Drug: Verinurad
Randomized subjects will receive oral dose of verinurad
Other Names:
  • verinurad ER 24 mg
  • verinurad IR 40 mg

Drug: Placebo
Randomized subjects will receive oral dose of placebo
Other Names:
  • verinurad matching placebo
  • allopurinol matching placebo

Drug: Allopurinol
Randomized subjects will receive oral dose of allpurinol (Treatment A and B)
Other Name: allopurinol 300 mg

Experimental: Treatment CBA
Subjects will receive a single dose of all 3 treatments (C, B and A) in a crossover design with wash-out periods of at least 7 days between each study dose administration.
Drug: Verinurad
Randomized subjects will receive oral dose of verinurad
Other Names:
  • verinurad ER 24 mg
  • verinurad IR 40 mg

Drug: Placebo
Randomized subjects will receive oral dose of placebo
Other Names:
  • verinurad matching placebo
  • allopurinol matching placebo

Drug: Allopurinol
Randomized subjects will receive oral dose of allpurinol (Treatment A and B)
Other Name: allopurinol 300 mg




Primary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) [ Time Frame: Visit 2,3,4:- Day 1: Pre-dose, 0.5,1,1.5,2, 3, 4, 5, 6, 7, 8 and 12 hours post-dose; Day 2: 24 and 36 hours post-dose; Day 3: 48 hours post-dose ]
    To assess the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supra-therapeutic exposure), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF interval analysis

  2. Baseline-corrected and placebo-adjusted QTcF interval (ΔΔQTcF) [ Time Frame: Screening; Visit 2,3,4:- Day -1, 1,2, 3; Follow up visit (7 to 10 days after the last dose) ]
    To assess the effect of a single dose of verinurad given as either a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supra-therapeutic exposure), both in combination with allopurinol 300 mg, on the QTcF interval compared to placebo using a concentration-QTcF interval analysis


Secondary Outcome Measures :
  1. Baseline-corrected heart rate (ΔHR) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation(supratherapeutic exposure), both in combination with allopurinol 300 mg

  2. Baseline-corrected and placebo-adjusted heart rate (ΔΔHR) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  3. Baseline-corrected RR interval (ΔRR interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  4. Baseline-corrected and placebo-adjusted RR interval (ΔΔRR interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  5. Baseline-corrected PR interval (ΔPR interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  6. Baseline-corrected and placebo-adjusted PR interval (ΔΔPR interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  7. Baseline-corrected and placebo-adjusted QRS interval (ΔQRS interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  8. Baseline-corrected and placebo-adjusted QRS interval (ΔΔQRS interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  9. Baseline-corrected QT interval (ΔQT interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  10. Baseline-corrected and placebo-adjusted QT interval (ΔΔQT interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  11. Baseline-corrected QTcF interval (ΔQTcF interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  12. Baseline-corrected and placebo-adjusted QTcF interval (ΔΔQTcF interval) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To investigate the effect of verinurad given either as a 24 mg ER8 formulation (therapeutic exposure) or a 40 mg IR formulation (supratherapeutic exposure), both in combination with allopurinol 300 mg

  13. Area under plasma concentration-time curve from zero to infinity (AUC) [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the pharmacokinetics (PK) of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  14. Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUC0-t) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects.

  15. Maximum observed plasma concentration (Cmax) [ Time Frame: Visit 2,3, and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2,3,4,5,6, 8 and 12 hour (h); Day 2: 24 and 36 h post-dose; Day 3: 48 h post dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  16. Time to reach maximum observed plasma concentration (tmax) [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  17. Time delay between drug administration and the first observed concentration in plasma (tlag) [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  18. Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  19. Time of last quantifiable plasma concentration (tlast) [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  20. Apparent total body clearance of drug from plasma after extravascular administration (parent drug only) [CL/F] [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  21. Apparent volume of distribution during the terminal phase after extravascular administration (parent drug only) [Vz/F] [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  22. Apparent volume of distribution at steady state (Vss/F) [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  23. Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) [ Time Frame: Visit 2, 3 and 4:- Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, and 12 h post-dose; Day 2: 24 and 36 h post-dose; Day 3: 48 h post-dose ]
    To assess the PK of verinurad and its metabolites (M1 and M8) and allopurinol and its metabolite (oxypurinol) in healthy subjects

  24. Number of subjects with abnormal haematology, clinical chemistry and urinalysis [ Time Frame: Screening; Visit 2,3 and 4:- Day -1, Day 3: 48 h post-dose, Follow up period ]
    To assess clinical chemistry/hematology/urinalysis as a variable of safety and tolerability of verinurad and allopurinol

  25. Number of subjects with abnormal blood pressure and pulse rate [ Time Frame: Screening; Visit 2,3 and 4:- Day -1, Day 1: pre-dose, 1 and 6 h post-dose; Day 2: 24 h post-dose; Day 3: 48 h post-dose, Follow up visit ]
    To assess vital signs as a variable of safety and tolerability of verinurad and allopurinol



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Provision of signed and dated, written informed consent prior to any study-specific procedures.
  2. Healthy male and female subjects aged 18 to 50 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
  3. Females must have a negative pregnancy test at Screening and on admission to the study centre must be:

(1) Not pregnant or currently lactating or breast-feeding. (2) Of non-childbearing potential confirmed at the Screening Visit by fulfilling one of the following criteria: (i) 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 >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 and 3 months after the Follow-up Visit.

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

5. Serum uric acid (sUA) <300 μmol/L at Screening (Visit 1) and sUA <330 μmol/L on Day -1 in every treatment period (Visit 2 to 4). Note: Since sUA levels might vary on a daily basis, subjects with sUA ≥330 μmol/L on Day -1 will be retested. Treatment on Day 1 will only be administered when the sUA level on Day -1 is <330 μmol/L upon retesting. Subjects with sUA ≥330 μmol/L despite retesting, may conduct the treatment period at a later date when they have sUA <330 μmol/L.

6. Must be able to swallow multiple capsules/tablets.

Exclusion criteria:

  1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
  2. 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.
  3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
  4. Subject has a positive test result for SARS-CoV-2 RT-PCR before randomisation.
  5. Subject has clinical signs and symptoms consistent with 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.
  6. History of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
  7. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, at Screening (Visit 1) as judged by the Investigator, including:

(1) Alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) (2) Aspartate aminotransferase (AST) >1.5 × ULN (3) Bilirubin (total) >1.5 × ULN (4) Gamma glutamyl transpeptidase (GGT) >1.5 × ULN 8. Any clinically significant abnormal findings in vital signs at Screening as judged by the Investigator, including:

(1) Systolic blood pressure <90 mmHg or >140 mmHg (2) Diastolic blood pressure <50 mmHg or >90 mmHg (3) Heart rate <50 or >90 bpm 9. Carrier of the HLA-B*58:01 allele. 10. Any clinically important abnormalities in rhythm, conduction or morphology of the 12 lead safety ECG and any clinically important abnormalities in the 12-lead safety ECG as considered by the Investigator that may interfere with the interpretation of QT interval corrected for heart rate using Fridericia's formula (QTcF), including abnormal ST T wave morphology, particularly in the Clinical Study Protocol (CSP)-defined primary lead for dECG analysis or left ventricular hypertrophy:

  1. Prolonged QTcF >450 ms or shortened QTcF <340 ms or family history of long QT syndrome.
  2. PR (PQ) interval shortening <120 ms (PR >110 ms but <120 ms is acceptable if there is no evidence of ventricular pre-excitation).
  3. PR (PQ) interval prolongation (>220 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block, or AV dissociation.
  4. Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS >110 ms. Subjects with QRS >110 ms but <115 ms are acceptable if there is no evidence of ventricular hypertrophy or pre-excitation.

11. Any positive result on Screening for serum hepatitis B surface antigen OR anti-HBc antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.

12. Suspected or known Gilbert's syndrome. 13. Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to Screening.

14. Known or suspected history of alcohol abuse or excessive intake of alcohol as judged by the Investigator. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g per day for women.

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

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

17. Previous hypersensitivity reaction to allopurinol or any URAT1 inhibitor. 18. Subjects who are pregnant, breast-feeding or planning to become pregnant (pregnancy is to be avoided for the entire study period and 3 months after the Follow up Visit).

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

20. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 × the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or within 5 half-lives (whichever is longer). Hormone replacement therapy is allowed for females.

21. Plasma donation within 1 month of Screening or any blood donation/blood loss >500 mL during the 3 months prior to Screening.

22. 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 IMP in this study.

Note: Subjects consented and screened, but not randomised in this study or a previous Phase I study, are not excluded.

23. Involvement of any AstraZeneca, Parexel or study site employee or their close relatives.

24. Subjects who have previously received verinurad. 25. Subjects who cannot communicate reliably with the Investigator and/or are not able to read, speak and understand the German language.

26. Judgment by the Investigator that the subject should not participate in the study if there are any ongoing or recent (ie, during the Screening Period) minor medical complaints that may interfere with the interpretation of the study data or are considered unlikely to comply with study procedures, restrictions and requirements.

27. Subjects who are vegans or have medical dietary restrictions. 28. Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

29. Subjects who are regularly exposed to COVID-19 (eg, health care professionals working in COVID-19 wards or at emergency departments) as part of their daily life.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04256629


Locations
Layout table for location information
Germany
Research Site
Berlin, Germany, 14050
Sponsors and Collaborators
AstraZeneca
Parexel
Investigators
Layout table for investigator information
Principal Investigator: Thomas Kӧrnicke, MD PAREXEL Early Phase Clinical Unit Berlin
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04256629    
Other Study ID Numbers: D5495C00012
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: September 7, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request 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.

Time Frame:

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Access Criteria:

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Randomised
Double-Blind
Placebo-Controlled
3-Period Crossover
Verinurad
Allopurinol
Phase 1
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Allopurinol
Verinurad
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Gout Suppressants
Antirheumatic Agents
Free Radical Scavengers
Antioxidants
Protective Agents
Physiological Effects of Drugs