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

NCT04550234 | Completed Phase 1 Results FDA Drug

• 1 other identifier: D5495C00014
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Kidney Disease

Keywords

3-period; Crossover; URAT1 inhibitor; Xanthine oxidase inhibitor

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  Day 1, Day 2, Day 3 and Day 4 of each Treatment Period

Secondary Outcomes (14)

• Cmax: Maximum Observed Plasma Drug Concentration

  Day 1, Day 2, Day 3 and Day 4 of each Treatment Period

• AUCinf: Area Under Plasma Concentration-time Curve From 0 to Infinity

  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

  Day 1, Day 2, Day 3 and Day 4 of each Treatment Period

• Tmax: Time to Reach Maximum Observed Plasma Concentration Following Drug Administration

  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

  Day 1, Day 2, Day 3 and Day 4 of each Treatment Period

Study Arms (5)

Treatment 1

EXPERIMENTAL

Subjects will receive verinurad prolonged release HPMC capsule and allopurinol tablet in fasted state on Day 1.

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.

Drug: Verinurad/Allopurinol FDC Capsule

Treatment 3

EXPERIMENTAL

Subjects will receive verinurad/allopurinol FDC capsule in fed state on Day 1.

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.

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.

Drug: Verinurad prolonged release gelatin Capsule

Interventions

Verinurad prolonged release HPMC capsule DRUG

Randomized subjects will receive oral dose of verinurad HPMC capsule.

Treatment 1; Treatment 4

Allopurinol Tablet DRUG

Randomized subjects will receive oral dose of allopurinol tablet.

Treatment 1; Treatment 4

Verinurad/Allopurinol FDC Capsule DRUG

Randomized subjects will receive oral dose of Verinurad/Allopurinol FDC capsule.

Treatment 2; Treatment 3

Verinurad prolonged release gelatin Capsule DRUG

Randomized subjects will receive oral dose of Verinurad gelatin capsule.

Treatment 5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• (ii) 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.

You may not qualify if:

• 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,
• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

Related Links

• D5495C00014 CSR Synopsis
• D5495C00014 Protocol

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Allopurinol; verinurad

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical study Information Center

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: April 13, 2021
• Primary Completion: July 15, 2021
• Study Completion: July 15, 2021
• Last Updated: May 10, 2023
• Results First Posted: May 10, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• 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 rerefer 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

Locations

DE (1)