A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 After Repeat Dose Administration in Participants Who Are Overweight or Obese

A Phase I Randomized, Single-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 Following Repeat Dose Administration in Participants With Overweight or Obesity

A study in healthy male and female participants of non-childbearing and childbearing potential who have overweight or obesity

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD6234; Drug: Placebo

Detailed Description

The study will comprise of:

• A Screening Period of maximum 32 days (from Day -35 to Day -3).
• A Treatment Period of 6 weeks (Cohort 1), 12 weeks (Cohort 2 and 3) and 26 weeks (Cohort 4) during which the participants will receive the study drug during residency at clinical unit.
• A Follow-up Visit after the last dose of study drug.

This study with repeated dosing of AZD6234 consists of 4 cohorts. For cohorts 1,2 and 3, eligible participants will be randomized to AZD6234 and placebo in a 3:1 ratio. For Cohort 4, eligible participants will be randomized in a 4:1:4:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 532-0003
    • Research Site
• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy male and female participants aged 18 to 55 years 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, must not be lactating and must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:

  1. Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
  2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
• Have a BMI between 25 and 40 kg/m2 inclusive (at the time of screening) and weigh at least 60 kg.
• Participant must have an evaluable, pre-randomization MRI, as confirmed by the core laboratory review (Cohort 4 only).
• Cohort 4 only: Females of childbearing potential who use adequate protection (oral contraceptives are not permitted).

Exclusion Criteria:

• History of any clinically important disease or disorder which, in the opinion of the Investigator, 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 IMP.
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal STT wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
• Known or suspected history of drug abuse, smoking, alcohol abuse or cotinine at screening.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD6234.
• Has received prescription or non-prescription medication for weight loss within the last 3 months.
• Self-reported weight change of > 5 kg in the last 3 months prior to screening.
• Previous or planned (within study period) bariatric surgery or fitting of a weight loss device (eg, gastric balloon or duodenal barrier).
• Participants who follow vegan diet or have medical dietary restrictions.
• Participants who cannot communicate reliably with the Investigator.
• Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
• Contra-indication to MRI: such as participants with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field; participants with history of extreme claustrophobia or participant cannot fit inside the MRI scanner cavity (Cohort 4 only).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants will receive repeated doses of AZD6234 or placebo via SC injection	Drug: AZD6234; Participants will receive repeated doses of AZD6234 as a solution via SC; Drug: Placebo; Participants will receive matching volumes of the placebo as a solution via SC
Experimental: Cohort 2; Participants will receive repeated doses of AZD6234 or placebo via SC injection	Drug: AZD6234; Participants will receive repeated doses of AZD6234 as a solution via SC; Drug: Placebo; Participants will receive matching volumes of the placebo as a solution via SC
Experimental: Cohort 3; Japanese participants will receive repeated doses of AZD6234 or placebo via SC injection	Drug: AZD6234; Participants will receive repeated doses of AZD6234 as a solution via SC; Drug: Placebo; Participants will receive matching volumes of the placebo as a solution via SC
Experimental: Cohort 4; Japanese participants with childbearing potential will receive repeated doses of AZD6234 or placebo via SC injection.	Drug: AZD6234; Participants will receive repeated doses of AZD6234 as a solution via SC; Drug: Placebo; Participants will receive matching volumes of the placebo as a solution via SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs) and Serious Adverse Events(SAE)	The safety and tolerability of repeated subcutaneous (SC) doses of AZD6234 compared to placebo will be assessed.	From Screening (Day -35 to Day -3) to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma drug concentration (Cmax)	The pharmacokinetics (PK) of AZD6234 following repeated SC doses of AZD6234 will be assessed.	From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
Area under the plasma concentration-time (AUClast)	The PK of AZD6234 following repeated SC doses of AZD6234 will be assessed.	From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
Area under plasma concentration-time curve from zero to infinity (AUCinf)	The PK of AZD6234 following repeated SC doses of AZD6234 will be assessed.	From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or Day 225 (Cohort 4)
Area under concentration time curve in the dosing interval (AUCtau)	The PK of AZD6234 following repeated SC doses of AZD6234 will be assessed.	From Day 1 to Day 78 (Cohort 1) or to Day 120 (Cohort 2 and 3) or to Day 225 (Cohort 4)
Change from baseline in body weight of participants	The effects of AZD6234 on body weight change from baseline with and without placebo correction will be assessed.	From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
Change from baseline in Body Mass Index (BMI) of participants	The effects of AZD6234 on body weight change from baseline with and without placebo correction will be assessed.	From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
Percentage change from baseline in fasting insulin	The effects of AZD6234 compared to placebo on fasting insulin will be assessed.	From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
Change from baseline in absolute level of fasting insulin of participants	The effects of AZD6234 compared to placebo on fasting insulin will be assessed.	From baseline (Day -1) to Day 43 (Cohort 1) or to Day 85 (Cohort 2 and 3) or to Day 183 (Cohort 4)
Prevalence of anti-drug antibodies (ADAs) to AZD6234	The immunogenicity of AZD6234 following repeated SC doses of AZD6234 will be assessed.	Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) or to Day 183 (Cohort 4)
Incidence of ADAs to AZD6234	The immunogenicity of AZD6234 following repeated SC doses of AZD6234 will be assessed.	Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) to Day 183 (Cohort 4)
ADA titer	The immunogenicity of AZD6234 following repeated SC doses of AZD6234 will be assessed.	Day 1, 15, 36, and 78 (Cohort 1); Day 1, 15, 29, 43, 78 and 120 (Cohort 2 and 3) or to Day 183 (Cohort 4)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2023
• Primary Completion (Actual): February 3, 2026
• Study Completion (Actual): March 7, 2026

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 10, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Overweight
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity
• Other Study ID Numbers: D8750C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing 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.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No