Clinical trial NCT06942923: A Study to Investigate the Safety, Tolerability and Pharmacodynamics of AZD4144 in Participants With Obesity
Official title: A Phase I, Randomised, Investigator- and Participant-blinded, Placebo-Controlled, Study to Assess the Safety, Tolerability, and Pharmacodynamics of AZD4144 in Participants With Obesity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Cardiorenal disease
Atherosclerotic cardiovascular disease
Chronic kidney disease
Type 2 Diabetes Mellitus
Atherosclerosis
Obesity
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2025-04-24
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the safety and tolerability, and pharmacodynamics (PD) of AZD4144 administered as repeated daily oral dosing.

Detailed description: This is placebo-controlled, parallel group and single centre study in healthy male and female participants with obesity and no known Atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or Type 2 Diabetes Mellitus.

Participants will be randomized in the ratio of 1:1 to receive either AZD4144 or placebo.

This study will comprise of:

* A screening period of 28 days.
* The treatment duration will be up to 28 days.
* The visit frequency will be weekly up to a Follow-up Visit, followed by a Final Follow-up Visit 28 days after the final dose of AZD4144.

Eligibility criteria: Key Inclusion Criteria:

* Serum hsCRP \> 2 milligrams per liter (mg/L).
* All females must have a negative pregnancy test at the Screening Visit and at the randomization visit (Visit 2).
* Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception to avoid pregnancy from the time of first administration of study intervention until 3 months after the Final Follow-up Visit.
* Have a body mass index (BMI) greater than or equal to (≥) 30 and less than or equal to (≤) 45 kilograms per meter\^2 (kg/m\^2).
* Have a waist to hip ratio of ≥0.9 for male and ≥0.85 for female participants.

Key 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 of Myocardial infarction (MI), coronary revascularisation, stroke, revascularisation for peripheral arterial disease, or other pre-existing Cardiovascular (CV) diseases.
* History of Diabetes (Type 1 and Type 2) or glycated haemoglobin (HbA1c) ≥6.5%.
* 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 skin disorder, history of, or ongoing clinically significant allergy/hypersensitivity.
* 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.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: From Screening (Day -28 to Day -2) to final follow-up (Day 56)
measure: Relative change from baseline in systemic interleukin-6 (IL-6) levels
timeFrame: From baseline to 4 weeks
Secondary outcomes:
measure: Relative change from baseline in systemic IL-18 levels
timeFrame: From baseline to 4 weeks
measure: Relative change from baseline in high-sensitivity C-reactive protein (hsCRP) levels
timeFrame: From baseline to 4 weeks
measure: Observed lowest concentration before the next dose is administered (Ctrough) of AZD4144
timeFrame: From Day 1 to Day 28
measure: Maximum observed drug concentration (Cmax) of AZD4144
timeFrame: From Day 1 to Day 28
measure: Time to reach maximum observed concentration (tmax) of AZD4144
timeFrame: From Day 1 to Day 28
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Research Site
Study officials:
References: