Zibotentan in Healthy Participants

AC
Overseen ByAstraZeneca Clinical Study Information Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the body processes a drug called Zibotentan in healthy individuals. Researchers aim to study the drug's absorption, distribution, metabolism, and elimination in both Non-Asian and Japanese participants. Participants will receive a single dose of Zibotentan on four separate occasions, with breaks in between. A suitable candidate for this trial is a healthy individual with veins appropriate for blood draws who meets specific ethnic criteria, such as Japanese ancestry. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescribed or nonprescribed medications, including antacids, pain relievers, herbal remedies, and vitamins, at least 2 weeks before starting the study.

Is there any evidence suggesting that Zibotentan is likely to be safe for humans?

Research has shown that Zibotentan is generally safe for patients. In earlier studies, no new major safety issues emerged. A small number of patients experienced changes in liver enzymes, indicating possible liver stress. Specifically, 0.4% of patients taking Zibotentan had increased liver enzymes, compared to 0.9% of those taking a placebo. This indicates that safety issues were rare and similar to those in people not taking the drug. Overall, past studies have demonstrated that Zibotentan is safe for most patients.12345

Why do researchers think this study treatment might be promising?

Zibotentan is unique because it targets the endothelin A receptor, which is a different approach compared to the standard treatments for conditions like prostate cancer and other cardiovascular issues. Most traditional options, like chemotherapy or hormone therapies, act broadly or on hormonal pathways. Zibotentan's specific mechanism allows it to potentially block harmful signals that contribute to disease progression, offering a more targeted treatment approach. Researchers are excited because this specificity might reduce side effects and improve outcomes compared to existing therapies.

What evidence suggests that Zibotentan could be effective?

Research has shown how zibotentan moves through the body. Previous studies found that about 58% of zibotentan is excreted through urine. Tests on individuals with moderate liver and kidney issues examined how these conditions affect the drug's processing. In a study on microvascular angina, zibotentan did not alter heart-related markers but did impact blood tests related to the liver, fats, and blood sugar. Although information on its effectiveness for other conditions is limited, these studies provide initial insights into the drug's handling by the body. Participants in this trial will receive zibotentan in different treatment sequences to further explore its pharmacokinetics.16789

Are You a Good Fit for This Trial?

This trial is for healthy non-Asian and Japanese individuals to study how the body processes different doses of Zibotentan, a medication potentially relevant for liver conditions. Specific eligibility details are not provided.

Inclusion Criteria

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
Provision of signed and dated, written informed consent prior to any study specific procedures
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Exclusion Criteria

Clinically significant abnormal findings in vital signs after 10 minutes of supine rest
Excessive intake of caffeine-containing drinks or food
I haven't taken any medication, including over-the-counter drugs and supplements, in the last 2 weeks.
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive four different single doses of zibotentan in a cross-over design, with each dose separated by washout periods

4 weeks
4 visits (in-person)

Washout

Washout periods between each treatment dose to ensure no carryover effects

6 days total

Follow-up

Participants are monitored for safety and effectiveness after the final treatment dose

1 week
1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • Zibotentan
Trial Overview The focus of this study is on measuring blood levels of Zibotentan at four varying oral doses in participants to understand its pharmacokinetics—how the drug is absorbed, distributed, metabolized, and excreted by the body.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: Treatment sequence DCBA: ZibotentanExperimental Treatment1 Intervention
Group II: Treatment sequence CADB: ZibotentanExperimental Treatment1 Intervention
Group III: Treatment sequence BDAC: ZibotentanExperimental Treatment1 Intervention
Group IV: Treatment sequence ABCD: ZibotentanExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials
322
Recruited
137,000+
Peyton Howell profile image

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith profile image

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Citations

Pharmacokinetics and Tolerability of Zibotentan in Patients ...This study evaluated the PK and tolerability of a single oral dose of zibotentan in participants with concurrent moderate renal impairment and moderate hepatic ...
2.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37801266/
Pharmacokinetics and Tolerability of Zibotentan in Patients ...This study evaluated the PK and tolerability of a single oral dose of zibotentan in participants with concurrent moderate renal impairment and moderate hepatic ...
A study to assess zibotentan pharmacokinetics in ...This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of zibotentan in patients with moderate hepatic and ...
Pharmacokinetics and tolerability of zibotentan (ZD4054) in ...The drug and its metabolites are predominantly eliminated in urine with ~58% of parent compound being eliminated by renal clearance. Metabolism ...
Zibotentan in Microvascular Angina: A Randomized ...Zibotentan was associated with changes in hematology, liver function, lipid profile, and glycated hemoglobin, but not cardiac biomarkers (Table ...
NCT05112419 | A Study to Assess Zibotentan ...This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a single oral dose of zibotentan in patients with moderate ...
Study to Investigate Efficacy, Safety, and Tolerability of ...This is a Phase III, randomised, multicentre, double-blinded study to evaluate efficacy, safety and tolerability of treatment with zibotentan/dapagliflozin ...
A comprehensive analysis of liver safety across zibotentan ...A total of 4 (0.4%) patients receiving zibotentan monotherapy experienced ALT elevations >5× ULN versus 8 (0.9%) receiving placebo. Of the seven patients ...
Zibotentan in Microvascular Angina: A Randomized ...Secondary outcomes showed no improvement with zibotentan. Zibotentan reduced blood pressure and increased plasma concentrations of ET-1. Adverse ...
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