A Study to Investigate the Blood Concentrations of 4 Different Oral Doses of Zibotentan in Healthy Non-Asian and Japanese Participants

NCT06715670 | Completed Phase 1 FDA Drug

• 1 other identifier: D4326C00010
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study aim to assess the Pharmacokinetics of Zibotentan in Healthy Non-Asian and Japanese Participants.

Conditions

Liver Cirrhosis

Keywords

Chronic kidney disease; Treatment sequence; Pharmacokinetics; Washout periods

Outcome Measures

Primary Outcomes (3)

• Area under concentration-time curve from time 0 to infinity (AUCinf)

  To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.

  Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)

• Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)

  To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants.

  Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)

• Maximum observed drug concentration (Cmax)

  To characterize the single-dose plasma PK of orally administered zibotentan in healthy non-Asian and Japanese participants

  Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)

Secondary Outcomes (12)

• Number of participants with adverse events (AEs) receiving single dose

  From Screening (28 days) to follow-up Visit 5 to 7 days post-final dose (approximately 9 weeks)

• Concentration at 24 hours post dose (C24)

  Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)

• Partial area under the concentration time curve from time 0 to 24 hours post-dose (AUC(0-24))

  Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)

• Time to reach maximum observed concentration (tmax)

  Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)

• Terminal elimination half-life (t1/2 λz)

  Day 1 through Day 3 of each Treatment Period (each Treatment Period is 7 days)

Study Arms (4)

Treatment sequence ABCD: Zibotentan

EXPERIMENTAL

Participants will receive single dose of Zibotentan in 4 occassions with first Treatment A, followed by Treatment B, Treatment C and then Treatment D with each dose separated by 3 washout periods.

Drug: Zibotentan

Treatment sequence BDAC: Zibotentan

EXPERIMENTAL

Participants will receive single dose of Zibotentan in 4 occassions with first Treatment B, followed by Treatment D, Treatment A and then Treatment C with each dose separated by 3 washout periods

Drug: Zibotentan

Treatment sequence CADB: Zibotentan

EXPERIMENTAL

Participants will receive single dose of Zibotentan in 4 occassions with first Treatment C, followed by Treatment A, Treatment D and then Treatment B with each dose separated by 3 washout periods.

Drug: Zibotentan

Treatment sequence DCBA: Zibotentan

EXPERIMENTAL

Participants will receive single dose of Zibotentan in 4 occassions with first Treatment D, followed by Treatment C, Treatment B and then Treatment A with each dose separated by 3 washout periods.

Drug: Zibotentan

Interventions

Zibotentan DRUG

Participant will receive 4 different single doses of zibotentan on Day 1 of each treatment period orally.

Treatment sequence ABCD: Zibotentan; Treatment sequence BDAC: Zibotentan; Treatment sequence CADB: Zibotentan; Treatment sequence DCBA: Zibotentan

Eligibility Criteria

• Age: 18 Years - 60 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 (non-childbearing potential) with suitable veins for cannulation or repeated venipuncture.
• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
• Females of non-childbearing potential must be confirmed at the Screening Visit.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
• Body mass index (BMI) between 18 and 32 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive at Screening.
• Japanese participant must have Japanese parents and grandparents, were born in Japan, and not have lived outside Japan for over 10 years.
• Participant is considered non-Asian if their parents and all grandparents are ethnically non-Asian.

You may not qualify if:

• History of any clinically important disease or disorder which may either put the participant at risk because of participation in the study or influence the results or the participant's ability to participate in the study.
• 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 illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis, laboratory values and vital signs at the Screening Visit.
• Any positive result on Screening for serum HBsAg (Hepatitis B surface antigen), HBcAb (Hepatitis B core antibody) or HIV (Human immunodeficiency virus).
• Clinically significant abnormal findings in vital signs after 10 minutes of supine rest.
• Clinically important abnormalities in rhythm, conduction, or morphology of the resting electrocardiography (ECG) and prolonged QTcF \> 450 ms, family history of long QT syndrome, or early cardiac death.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
• Positive screen for drugs of abuse or alcohol at Screening or first admission.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
• Excessive intake of caffeine-containing drinks or food.
• Use of any prescribed or nonprescribed medication, including antacids, analgesics, herbal remedies, mega dose vitamins, and minerals within 2 weeks before the first administration of the study intervention.
• Plasma donation within one month of the Screening Visit or any blood donation/blood loss \> 500 mL during the 3 months before the Screening Visit.
• Receipt of another new chemical entity within 30 days or 5 half-lives (whichever is longest) of the first administration of the study intervention.
• Previous receipt of zibotentan within 28 days before Day 1 dosing in the Clinical Unit.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Liver Cirrhosis; Renal Insufficiency, Chronic

Interventions

ZD4054

Condition Hierarchy (Ancestors)

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

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: November 29, 2024
• First Posted: December 4, 2024
• Study Start: December 5, 2024
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA 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 anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (1)