A Study to Assess the Relative Bioavailability of 3 Different Formulations Under Fasted and Fed Condition

NCT04024501 | Completed Phase 1 Results FDA Drug

• 1 other identifier: D5495C00005
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study is intended to assess the relative bioavailability between the (extended-release) ER8 capsule formulation (the formulation that is currently used for verinurad development) given under fasted conditions and 2 new capsule formulations of verinurad (A-capsule and B-capsule) given under fed or fasted conditions. All three capsules target an 8-hour release profile (extended-release). The highest dose (12 mg) currently tested in participants will be tested in this study. The study is designed to provide information to optimize the verinurad part of a fixed dose combination capsule to be used in future development.

Conditions

Chronic Kidney Disease

Keywords

URAT1 inhibitor; Uric acid transporter 1; Verinurad; Crossover study; Relative bioavailability; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• Area Under Plasma Concentration-time Curve From Zero to Infinity (AUC)

  To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.

  Day 1: Pre-dose and up to 72-hour Post-dose

• AUC From Time 0 to the Last Quantifiable Concentration (AUC0-t) for the Analysis of PK Parameter

  To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.

  Day 1: Pre-dose and up to 72-hour Post-dose

• Maximum Observed Plasma Concentration (Cmax) for the Analysis of PK Parameter

  To evaluate the relative bioavailability between the A-capsule and B-capsule formulations under both fed and fasted conditions with the ER8 capsule formulation under fasted conditions and with each other under the same food conditions.

  Day 1: Pre-dose and up to 72-hour Post-dose

Secondary Outcomes (9)

• AUC From Time 0 to 24 Hours Post Dose (AUC0-24) for the Analysis of PK Parameter

  Pre-dose and up to 24-hours Post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax) for the Analysis of PK Parameter

  Day 1: Pre-dose and up to 72-hour Post-dose

• Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) for the Analysis of PK Parameter

  Day 1: Pre-dose and up to 72-hour Post-dose

• Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F) for the Analysis of PK Parameter

  Day 1: Pre-dose and up to 72-hour Post-dose

• Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRT) for the Analysis of PK Parameter

  Day 1: Pre-dose and up to 72-hour Post-dose

Study Arms (5)

Treatment 1

EXPERIMENTAL

During this treatment period, healthy participants will receive 1 x 12 mg verinurad ER8 capsule formulation in fasted state.

Drug: Verinurad ER8 capsule formulation (fasted)

Treatment 2

EXPERIMENTAL

During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fasted state.

Drug: Verinurad A-capsule formulation (fasted)

Treatment 3

EXPERIMENTAL

During this treatment period, healthy participants will receive 2 x 6 mg verinurad A-capsule formulation in fed state.

Drug: Verinurad A-capsule formulation (fed)

Treatment 4

EXPERIMENTAL

During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fasted state.

Drug: Verinurad B-capsule formulation (fasted)

Treatment 5

EXPERIMENTAL

During this treatment period, healthy participants will receive 2 x 6 mg verinurad B-capsule formulation in fed state.

Drug: Verinurad B-capsule formulation (fed)

Interventions

Verinurad ER8 capsule formulation (fasted) DRUG

Each participant will receive single-dose treatment of 12 mg verinurad ER8 capsule with 240 mL water, following an overnight fast of at least 10 hours.

Treatment 1

Verinurad A-capsule formulation (fasted) DRUG

Each participant will receive single-dose treatment of 12 mg verinurad A-capsule with 240 mL water, following an overnight fast of at least 10 hours.

Treatment 2

Verinurad A-capsule formulation (fed) DRUG

Each participant will receive single dose treatment of 12 mg verinurad A-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).

Treatment 3

Verinurad B-capsule formulation (fasted) DRUG

Each participant will receive single-dose treatment of 12 mg verinurad B-capsule with 240 mL water, following an overnight fast of at least 10 hours.

Treatment 4

Verinurad B-capsule formulation (fed) DRUG

Each participant will receive single dose treatment of 12 mg verinurad B-capsule with 240 mL water, following a high-fat, high-calorie breakfast (after the overnight fast).

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 participants aged 18 to 50 years with suitable veins for cannulation or repeated venepuncture.
• Have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg.
• 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 amenorrhoea for at least 12 months or more following cessation of all exogenous hormonal treatments and 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.

You may not qualify if:

• History of gout or any clinically significant disease or disorder 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 (GI), 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 (ALT) \> 1.5 x upper limit of normal (ULN), (2) Aspartate aminotransferase (AST) \> 1.5 x ULN, (3) Bilirubin (total) \> 1.5 x ULN, (4) Gamma glutamyl transpeptidase (GGT) \> 1.5 x ULN. (5) If any of these tests are out-of-range, the tests can be repeated once.
• 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) Heart rate (resting, supine) \< 50 beats per minute (bpm) or \> 85 bpm, (2) Systolic BP \< 90 mmHg or \> 140 mmHg and/or diastolic BP \< 50 mmHg or \> 90 mmHg sustained for \> 10 min 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:
• ECG interval measured from the onset of the QRS complex to the end of the T wave (QT) interval corrected for heart rate using Fridericia's formula (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 atrioventricular (AV) block, or AV dissociation,
• Complete bundle branch block and/or QRS duration \> 120 ms. 7. Any positive result at the Screening Visit for serum hepatitis B surface antigen or antiHBc antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• \. Suspicion or known Gilbert's and/or Lesch-Nyhan syndrome. 9. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol as judged by the PI. Excessive intake of alcohol defined as the regular consumption of more than 24 g of alcohol per day for men or 12 g of alcohol per day for women.
• \. Has received another new chemical entity (defined as a compound which has not been approved for marketing in the US) within 30 days or at least 5 half-lives (whichever is longer) of the first administration of verinurad in this study.
• \. Participants who have previously received verinurad. 12. 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

Related Links

• redacted CSP and SAP

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Dosage Forms

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)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Results Point of Contact

• Title: AstraZeneca information Centre
• Organization: AstraZeneca

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: July 16, 2019
• First Posted: July 18, 2019
• Study Start: July 20, 2019
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: March 18, 2021
• Results First Posted: August 21, 2020

Record last verified: 2021-02

Locations

DE (1)