A Study in Healthy Subjects to Assess Drug Availability of 2 Different Formulations of Verinurad and Allopurinol

A Randomised, Single-dose, 3-period, 3-treatment, Crossover Study to Assess the Relative Bioavailability of 2 Different Formulations of Verinurad and Allopurinol in Healthy Subjects

Sponsors

Lead Sponsor: AstraZeneca

Collaborator: Parexel

Source AstraZeneca
Brief Summary

This study is a single centre, randomised, open-label, single-dose, 3-period, 3-treatment, crossover study in healthy male and female subjects. This study is intended to assess the relative bioavailability between the ph3 (fixed dose combination) and ph2b (free combination) formulations of verinurad and allopurinol. For verinurad, both formulations have an extended release profile. For allopurinol, both formulations have an immediate release profile.

Detailed Description

The study comprises of: - A Screening Period of maximum 28 days; - Three treatment periods during which subjects will be resident from the morning of the day before first dosing (Day -1 of Treatment Period 1) until at least 72 hours after dosing in Treatment Period 3; discharged on the morning of Day 4 of Treatment Period 3; and - A Follow-up Visit 7 to 14 days after the last dosing. Each subject will receive 3 single dose treatments of verinurad and allopurinol. and subject will be involved in the study for 46 to 53 days.

Overall Status Not yet recruiting
Start Date October 15, 2020
Completion Date December 15, 2020
Primary Completion Date December 15, 2020
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Evaluation of the relative bioavailability of verinurad, allopurinol and oxypurinol after dosing with the ph3 and ph2b formulations under fasted conditions by AUCinf Days 1 to 4: pre-dose and upto 72 hours post-dose
Evaluation of the relative bioavailability of verinurad, allopurinol and oxypurinol after dosing with the ph3 and ph2b formulations under fasted conditions by AUClast Days 1 to 4: pre-dose and upto 72 hours post-dose
Evaluation of the relative bioavailability of verinurad, allopurinol and oxypurinol after dosing with the ph3 and ph2b formulations under fasted conditions by Cmax Days 1 to 4: pre-dose and upto 72 hours post-dose
Secondary Outcome
Measure Time Frame
Evaluation of the relative bioavailability of verinurad, allopurinol and oxypurinol after dosing with the ph3 formulation under fed and fasted conditions by AUCinf Days 1 to 4: pre-dose and upto 72 hours post-dose
Evaluation of the relative bioavailability of verinurad, allopurinol and oxypurinol after dosing with the ph3 formulation under fed and fasted conditions by AUClast Days 1 to 4: pre-dose and upto 72 hours post-dose
Evaluation of the relative bioavailability of verinurad, allopurinol and oxypurinol after dosing with the ph3 formulation under fed and fasted conditions by Cmax Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by AUCinf Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by AUClast Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by Cmax Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by tmax Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by tlag Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by λz Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by t½λz Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by CL/F Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by MRTinf Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by Vss/F Days 1 to 4: pre-dose and upto 72 hours post-dose
Assessment of the pharmacokinetic profiles of verinurad, allopurinol and oxypurinol when administered as the ph3 formulation under fed and fasted conditions and the ph2b formulation in the fasted state by Vz/F Days 1 to 4: pre-dose and upto 72 hours post-dose
Number of subjects with serious and non-serious adverse events From Screening (Days -28 to -2) to follow-up visit (7 to 14 days post final dose)
Enrollment 15
Condition
Intervention

Intervention Type: Drug

Intervention Name: Verinurad

Description: Randomized subjects will receive oral dose of verinurad.

Intervention Type: Drug

Intervention Name: Allopurinol

Description: Randomized subjects will receive oral dose of allopurinol.

Eligibility

Criteria:

Inclusion Criteria: - 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: 1. not pregnant or currently lactating or breastfeeding. 2. of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria: (i) postmenopausal defined as 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). (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. - Must be able to swallow multiple capsules and tablets. Exclusion Criteria: - 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: 1. Alanine aminotransferase > 1.5 x upper limit of normal (ULN), 2. Aspartate aminotransferase > 1.5 x ULN, 3. Bilirubin (total) > 1.5 x ULN, 4. 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: 1. Pulse (resting, supine) < 50 beats per minute (bpm) or > 90 bpm, 2. 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: 1. QTcF > 450 ms or < 340 ms or family history of long QT syndrome, 2. Any significant arrhythmia 3. Conduction abnormalities 4. Clinically significant PR (PQ) interval prolongation (> 240 ms); intermittent second or third degree AV block, or AV dissociation 5. 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 50 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Contact

Last Name: AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Email: [email protected]

Location
Facility: Research Site
Location Countries

Germany

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Treatment 1

Type: Active Comparator

Description: Eligible subjects will receive verinurad ph2b (free combination) capsule and allopurinol ph2b tablet in fasted state on Day 1.

Label: Treatment 2

Type: Experimental

Description: Eligible subjects will receive verinurad and allopurinol ph3 (fixed dose combination) capsule in fasted state on Day 1.

Label: Treatment 3

Type: Experimental

Description: Eligible subjects will receive verinurad and allopurinol ph3 (fixed dose combination) capsule in fed state on Day 1.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov