A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.

NCT06381466 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: D7250C00001
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of AZD0233 following single and multiple ascending dose (SAD and MAD) administration in healthy participants.

Conditions

Dilated Cardiomyopathy

Keywords

Heart failure; Single Ascending Dose (SAD); Multiple Ascending Dose (MAD); Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events (AEs) and serious adverse events (SAEs)

  To assess the safety and tolerability of AZD0233 following oral administration of single ascending doses (Part A) and multiple ascending doses (Part B) and to estimate the maximum tolerated dose (if within pre-defined exposure limits).

  From screening (Day -28) to follow-up visit (Day 17)

Secondary Outcomes (14)

• Maximum observed plasma (peak) drug concentration (Cmax) of AZD0233

  Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)

• Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD0233

  Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)

• Area under the concentration-time curve in the dose interval (AUCtau) of AZD0233

  Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)

• Area under plasma concentration time-curve from zero to infinity (AUCinf) of AZD0233

  Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)

• Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD0233

  Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)

Study Arms (11)

Part A (SAD): Cohort 1A - AZD0233 (dose 1)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 1) orally as a single ascending dose.

Drug: AZD0233

Part A (SAD): Cohort 2A - AZD0233 (dose 2)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 2) orally as a single ascending dose.

Drug: AZD0233

Part A (SAD): Cohort 3A - AZD0233 (dose 3)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 3) orally as a single ascending dose.

Drug: AZD0233

Part A (SAD): Cohort 4A - AZD0233 (dose 4)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 4) orally as a single ascending dose.

Drug: AZD0233

Part A (SAD): Cohort 5A - AZD0233 (dose 5)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 5) orally as a single ascending dose.

Drug: AZD0233

Part B (MAD): Cohort 1B - AZD0233 (dose 6)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 6) orally as a multiple ascending dose.

Drug: AZD0233

Part B (MAD): Cohort 2B - AZD0233 (dose 7)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 7) orally as a multiple ascending dose.

Drug: AZD0233

Part B (MAD): Cohort 3B - AZD0233 (dose 8)

EXPERIMENTAL

Healthy participants will receive AZD0233 (dose 8) orally as a multiple ascending dose.

Drug: AZD0233

Part A (SAD): Placebo cohort

PLACEBO COMPARATOR

Healthy participants will receive placebo orally as a single ascending dose.

Drug: AZD0233 Placebo

Part B (MAD): Placebo cohort

PLACEBO COMPARATOR

Healthy participants will receive placebo orally as a multiple ascending dose.

Drug: AZD0233 Placebo

Part A (SAD): Food Effect (FE) extended Cohort 3A

EXPERIMENTAL

Healthy participants from Cohort 3A will participate in this extended cohort after a washout period of 24 hours.

Drug: AZD0233

Interventions

AZD0233 DRUG

Randomized participants will receive AZD0233 orally as a single ascending dose (dose 1, dose 2, dose 3, dose 4 or dose 5) or multiple ascending dose (dose 6, dose 7 or dose 8)

Part A (SAD): Cohort 1A - AZD0233 (dose 1); Part A (SAD): Cohort 2A - AZD0233 (dose 2); Part A (SAD): Cohort 3A - AZD0233 (dose 3); Part A (SAD): Cohort 4A - AZD0233 (dose 4); Part A (SAD): Cohort 5A - AZD0233 (dose 5); Part A (SAD): Food Effect (FE) extended Cohort 3A; Part B (MAD): Cohort 1B - AZD0233 (dose 6); Part B (MAD): Cohort 2B - AZD0233 (dose 7); Part B (MAD): Cohort 3B - AZD0233 (dose 8)

AZD0233 Placebo DRUG

Randomized participants will receive matching placebo orally as a SAD or MAD.

Also known as: Placebo

Part A (SAD): Placebo cohort; Part B (MAD): Placebo cohort

Eligibility Criteria

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

You may qualify if:

• Healthy male and/or female participants 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 by fulfilling one of the following criteria:
• Post-menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post-menopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the specified contraception methods from the time of first administration of study intervention until 3 months after the study Follow-up Visit.
• Have a body mass index between 18 and 30 kg/m² inclusive and weigh at least 50 kg.
• Note: For Japanese sub-Cohort minimum weight of 45 kg is acceptable.
• For the healthy Japanese sub-Cohorts: healthy Japanese participants (e.g., natives of Japan or Japanese Americans) are defined as having both parents and 4 grandparents who are Japanese. This includes healthy second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.

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, urinalysis, laboratory values or vital signs at Screening and/or first admission to the Clinical Unit.
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-lead ECG that may interfere with the interpretation of corrected QT (QTc) interval changes in heart rate.
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the previous 3 months prior to Screening.
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
• Positive screen for drugs of abuse, or alcohol or cotinine at Screening or on each admission to the Clinical Unit.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs of a similar class to AZD0233.
• Use of drugs with enzyme \[Cytochrome P450 3A (CYP3A)\]/ transporter \[breast cancer resistance protein (BCRP) and organic anion transporting polypeptide 1B (OATP1B)\] inducing/ inhibiting properties such as St John's Wort within 3 weeks prior to the first administration of study intervention.
• Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of study intervention or longer if the medication has a long half-life. Hormone replacement therapy medications are allowed for female participants.
• Participants who have previously received AZD0233.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing or presence of fever (confirmed tympanic body temperature \> 37.6 °C) within 14 days prior to dosing on Day 1 depending on experienced symptoms.
• Clinically significant serious active and chronic infections within 60 days prior to randomization.
• Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Heart Failure

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: April 24, 2024
• Study Start: April 1, 2024
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: January 26, 2026

Record last verified: 2026-01

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)