A Study to Investigate How AZD4144 Affects the Pharmacokinetics of Rosuvastatin in Healthy Participants

An Open-label, 2-period, 2-sequence Cross-over Study to Assess the Effect of AZD4144 on the Pharmacokinetics of Rosuvastatin in Healthy Participants

The purpose of this study is to evaluate the pharmacokinetics (PK) of rosuvastatin when administered alone and in combination with single oral dose of AZD4144.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: AZD4144; Drug: Rosuvastatin

Detailed Description

This is a Phase 1, randomized, open label study in healthy participants.

The participants will be provided with:

Treatment A: single dose of rosuvastatin Treatment B: single dose of rosuvastatin in combination with AZD4144. The participants will be randomized in the 1:1 ratio to either receive treatment sequence AB or sequence BA.

The study will be comprised of:

• A screening period of 28 days.
• Two treatment periods (Treatment period 1 and Treatment period 2) of 4 days each where participants will receive the study intervention on Day 1 in Treatment period 1 and on Day 10 in Treatment period 2.
• A final Follow-up visit between Day 17 and Day 20.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have a body mass index between 18 and 32 kg/m2 inclusive at the Screening Visit and on first admission (Visit 2) to the Clinical Unit and weigh at least 45 kg.
• All females must have a negative pregnancy test at the Screening Visit.
• Female participants of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception.
• Females of non-childbearing potential must be confirmed at the Screening Visit.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.

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.
• Clinically significant serious active and chronic infections within 60 days prior to randomisation.
• 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 randomisation.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing or presence of fever (confirmed tympanic body temperature > 37.5 °C) within 14 days prior to dosing on Day 1 depending on experienced symptoms.
• Bacillus Calmette-Guérin vaccine within one year prior to signing the ICF.
• Any laboratory values with deviations at the Screening Visit or on admission to the Clinical Unit. Abnormal values may be repeated at the discretion of the Investigator: alanine transaminase (ALT) >1.00 × Upper Limit Normal (ULN), aspartate transaminase (AST) > 1.00 ×ULN, white blood cell count < Lower limit normal (LLN), differential neutrophils < LLN, bilirubin > 1.00 × ULN, eGlomerular filtration rate (eGFR) < 60 mL/min/1.73 m² calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR will only be assessed at Screening).
• Any positive result at Screening for serum hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or human immunodeficiency virus.
• Has received any investigational medicinal product.
• Participants who have previously received AZD4144.
• Participants with myopathy, defined as muscle weakness that in opinion of the investigator, enhances the participant's risk of developing statin-associated muscle symptoms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment sequence AB; Participants will receive single dose of rosuvastatin under fasted condition (Treatment A), followed by a single dose of rosuvastatin with AZD4144 under fasted condition (Treatment B).	Drug: AZD4144; Oral tablet of AZD4144 will be administered.; Drug: Rosuvastatin; Oral tablet of rosuvastatin will be administered.
Experimental: Treatment sequence BA; Participants will receive a single dose of rosuvastatin with AZD4144 under fasted condition (Treatment B), followed by a single dose of rosuvastatin under fasted condition (Treatment A).	Drug: AZD4144; Oral tablet of AZD4144 will be administered.; Drug: Rosuvastatin; Oral tablet of rosuvastatin will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve from 0 to infinity (AUCinf)	The AUCinf of rosuvastatin when administered alone and in combination with AZD4144 in healthy participants will be evaluated.	Day 1 to Day 4 and Day 10 to Day 13
Area under the plasma concentration-curve from 0 to the last quantifiable concentration (AUClast)	The AUClast of rosuvastatin when administered alone and in combination with AZD4144 in healthy participants will be evaluated.	Day 1 to Day 4 and Day 10 to Day 13
Maximum plasma drug concentration (Cmax)	The Cmax of rosuvastatin when administered alone and in combination with AZD4144 in healthy participants will be evaluated.	Day 1 to Day 4 and Day 10 to Day 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events	The safety and the tolerability of AZD4144 in combination with rosuvastatin will be evaluated.	From screening (Day-28 to Day -2) until Follow-up (Day 20)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2025
• Primary Completion (Actual): June 12, 2025
• Study Completion (Actual): June 12, 2025

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 7, 2025
• First Posted (Actual): April 13, 2025

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Nucleotide-binding domain,; leucine-rich-containing family, pyrindomain-containing-3 (NLRP3) inflammasome
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: D9441C00002

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. 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 shared

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma 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 researchenvironmentVivli.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: No
• Studies a U.S. FDA-regulated device product: No