Healthy Participants
Conditions
Keywords
Cardiorenal disease, Atherosclerotic cardiovascular disease, Chronic kidney disease, Type 2 Diabetes Mellitus, Atherosclerosis, Obesity
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.
Interventions
DRUGAZD4144
AZD4144 will be administered orally as per arms they have been assigned.
DRUGPlacebo
Placebo will be administered orally as per arms they have been assigned.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion 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). 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) | From Screening (Day -28 to Day -2) to final follow-up (Day 56) | The safety and tolerability of AZD4144 compared with placebo will be assessed. |
| Relative change from baseline in systemic interleukin-6 (IL-6) levels | From baseline to 4 weeks | The effect of AZD4144 on circulating inflammatory biomarker IL-6 compared with placebo will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Observed lowest concentration before the next dose is administered (Ctrough) of AZD4144 | From Day 1 to Day 28 | The pharmacokinetics (PK) of AZD4144 in participants with obesity will be assessed. |
| Relative change from baseline in systemic IL-18 levels | From baseline to 4 weeks | The effect of AZD4144 compared with placebo on circulating biomarker IL-18 will be assessed. |
| Time to reach maximum observed concentration (tmax) of AZD4144 | From Day 1 to Day 28 | The PK of AZD4144 in participants with obesity will be assessed. |
| Maximum observed drug concentration (Cmax) of AZD4144 | From Day 1 to Day 28 | The PK of AZD4144 in participants with obesity will be assessed. |
| Relative change from baseline in high-sensitivity C-reactive protein (hsCRP) levels | From baseline to 4 weeks | The effect of AZD4144 compared with placebo on circulating biomarker hsCRP will be assessed. |
Countries
Germany
Outcome results
None listed