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

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06132841
• Other study ID #: D8750C00002
• Status: Recruiting
• Phase: Phase 1
• Start date: November 13, 2023
• Est. completion date: April 30, 2025

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 during which the participants will receive the study drug during residency at clinical unit. - A Follow-up Visit (Day 78) after the last dose of study drug. This study with repeated dosing of AZD6234 consists of 2 cohorts. Eligible participants will be randomized to AZD6234 and placebo in a 3:1 ratio.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
• 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.

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 are vegans 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.

Related Conditions & MeSH terms

• Healthy Participants
• Overweight

Intervention

Drug:
• AZD6234
Participants will receive repeated doses of AZD6234 as a solution via SC
• Placebo
Participants will receive matching volumes of the placebo as a solution via SC

Locations

Country	Name	City	State
Germany	Research Site	Berlin
United Kingdom	Research Site	Harrow
United States	Research Site	Brooklyn	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Parexel

Countries where clinical trial is conducted

United States,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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) until Day 78
Secondary	Maximum observed plasma drug concentration (Cmax)	The pharmacokinetics (PK) of AZD6234 following repeated SC doses of AZD6234 will be assessed.	From Day 1 until Day 78
Secondary	Area under the plasma concentration-time (AUClast)	The PK of AZD6234 following repeated SC doses of AZD6234 will be assessed.	From Day 1 until Day 78
Secondary	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 until Day 78
Secondary	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 until Day 78
Secondary	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
Secondary	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
Secondary	Percentage change from baseline in fasting insulin	The effects of AZD6234 compared to placebo on fasting insulin will be assessed.	From baseline (pre-dose Day 1) to Day 43
Secondary	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 (pre-dose Day 1) to Day 43
Secondary	Incidence of anti-drug antibodies (ADAs) to AZD6234	The immunogenicity of AZD6234 following repeated SC doses of AZD6234 will be assessed.	Day 1, Day 15, Day 36 and Day 78
Secondary	ADA titer	The immunogenicity of AZD6234 following repeated SC doses of AZD6234 will be assessed.	Day 1, Day 15, Day 36 and Day 78