A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4144 as Well as the Impact of AZD4144 on the Pharmacokinetics of Rosuvastatin and Furosemide in Healthy Participants

A Phase I Randomized, Single-blind, Placebo-controlled, and Sequential Group Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4144 Following Single and Multiple Ascending Doses Via Intravenous Administration, and an Open-label, 2-Period, 2-Sequence, Cross-over Study to Assess the Effects of Intravenous AZD4144 on Rosuvastatin and Furosemide Pharmacokinetics in Healthy Participants

This study consists of 3 parts: Part A, Part B and Part C. This study will compare the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD4144 with placebo in healthy participants, in Part A and Part B. Part C of this study will investigate the possibility of drug-drug interaction (DDI) between IV AZD4144 and oral rosuvastatin and furosemide by evaluating the PK of rosuvastatin and furosemide when administered alone and in combination with single IV dose of AZD4144

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD4144- Part A; Drug: AZD4144- Part B; Drug: Placebo- Part A; Drug: Placebo- Part B; Drug: Rosuvastatin and Furosemide- Part C; Drug: Rosuvastatin, Furosemide, and AZD4144 Part C

Detailed Description

This is a Phase I, randomized study in healthy participants and consists of 3 parts; Part A, Part B and Part C. Part A and B are single-blind, placebo-controlled with single ascending dose (SAD) and multiple ascending dose (MAD) sequential group design, respectively. Part C is an open-label, 2-period, 2-sequence, cross-over design study. Part A and B of the study will assess the safety, tolerability, PK, and PD of AZD4144 solution for infusion compared with placebo while Part C will investigate the possibility of DDI between IV AZD4144 and oral rosuvastatin and furosemide by evaluating the PK of rosuvastatin and furosemide when administered alone and in combination with single IV dose of AZD4144

The study will comprise of:

• A screening period of maximum 28 days.

• A residential period which lasts from,

  • Day -1 to Day 4 (single dose on Day 1) for Part A
  • Day -1 to Day 15 (dosed on days 1, 4-12) for Part B
  • Day -1 to Day 3 (dose on Day 1) and Day 9 to Day 12 (dose on Day 10) for Part C

• A final follow-up visit,

  • On Day 10+3 for Part A
  • On Day 20+3 for Part B and C

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Contacts and Locations

Study Locations

• 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
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
• Females 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.
• Have a BMI between 18 and 32 kg/m2 inclusive at both Screening and Admission and weigh at least 45 kg at Screening.
• For healthy Japanese cohorts (Part A2 and Part B2): healthy male and female participants are to be Japanese, defined as having both parents and 4 grandparents who are Japanese. This includes second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
• For healthy Chinese cohort (Part A3): healthy male and female Chinese participants for whom both parents and all grandparents are Chinese and not lived outside of China for more than 10 years.

Exclusion Criteria:

• History of any clinically important disease or disorder 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.
• Clinically significant serious active and chronic infections.
• Any history or evidence of TB (active or latent).
• Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
• Bacillus Calmette Guérin vaccine within one year prior to signing the ICF.
• Any abnormal laboratory values at the Screening Visit or on Admission to the Clinical Unit.
• Any positive result on Screening for serum Hepatitis B surface antigen (HBsAg), anti-Hepatitis B core (HBc), hepatitis C antibody, or Human immunodeficiency virus (HIV).
• Any clinically important abnormalities in ECG.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
• Known hypersensitivity to furosemide and rosuvastatin (for Part C only)
• History of alcohol abuse or excessive intake of alcohol or current smokers or those who have smoked or used nicotine products.
• Use of drugs with enzyme inducing properties or of any prescribed or nonprescribed medication or of systemic hormonal contraceptives.
• Clinical signs and symptoms consistent with COVID-19.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

17

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A1-Cohort 1; Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144- Part A; Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.
Experimental: Part A1- Cohort 2; Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144- Part A; Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.
Experimental: Part A1-Cohort 3; Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144- Part A; Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.
Experimental: Part A2-Japanese cohort 1; Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144- Part A; Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.
Experimental: Part A2: Japanese Cohort 2; Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144- Part A; Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.
Experimental: Part A3-Chinese Cohort; Participants will receive one single ascending dose of AZD4144.	Drug: AZD4144- Part A; Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.
Experimental: Part B1- Cohort 1; Participants will receive multiple ascending doses of AZD4144.	Drug: AZD4144- Part B; Part B: Participants will be administered a single dose of AZD4144 on Day 1 and Day 12 via IV infusion. Participants will be administered multiple doses of AZD4144 from Day 4 to Day 11 via IV infusion.
Experimental: Part B1- Cohort 2; Participants will receive multiple ascending doses of AZD4144.	Drug: AZD4144- Part B; Part B: Participants will be administered a single dose of AZD4144 on Day 1 and Day 12 via IV infusion. Participants will be administered multiple doses of AZD4144 from Day 4 to Day 11 via IV infusion.
Experimental: Part B1- Cohort 3; Participants will receive multiple ascending doses of AZD4144.	Drug: AZD4144- Part B; Part B: Participants will be administered a single dose of AZD4144 on Day 1 and Day 12 via IV infusion. Participants will be administered multiple doses of AZD4144 from Day 4 to Day 11 via IV infusion.
Experimental: Part B2- Japanese Cohort; Participants will receive multiple ascending doses of AZD4144.	Drug: AZD4144- Part B; Part B: Participants will be administered a single dose of AZD4144 on Day 1 and Day 12 via IV infusion. Participants will be administered multiple doses of AZD4144 from Day 4 to Day 11 via IV infusion.
Placebo Comparator: Part A1- Placebo; Participants will receive matching placebo.	Drug: Placebo- Part A; Part A: Participants will be administered a single dose of placebo on Day 1 via IV infusion.
Placebo Comparator: Part A2- Placebo; Participants will receive matching placebo.	Drug: Placebo- Part A; Part A: Participants will be administered a single dose of placebo on Day 1 via IV infusion.
Placebo Comparator: Part A3- Placebo; Participants will receive matching Placebo.	Drug: Placebo- Part A; Part A: Participants will be administered a single dose of placebo on Day 1 via IV infusion.
Placebo Comparator: Part B1- Placebo; Participants will receive matching Placebo.	Drug: Placebo- Part B; Part B: Participants will be administered a single dose of placebo on Day 1 and Day 12via IV infusion. Participants will be administered multiple doses of placebo from Day 4 to Day 11 via IV infusion.
Placebo Comparator: Part B2- Placebo; Participants will receive matching Placebo.	Drug: Placebo- Part B; Part B: Participants will be administered a single dose of placebo on Day 1 and Day 12via IV infusion. Participants will be administered multiple doses of placebo from Day 4 to Day 11 via IV infusion.
Experimental: Part C Cohort- Treatment C1; Participants will receive rosuvastatin and furosemide.	Drug: Rosuvastatin and Furosemide- Part C; Participants will be administered a single oral dose of 10 mg Rosuvastatin and 1 mg Furosemide.
Experimental: Part C cohort- Treatment C2; Participants will receive rosuvastatin, furosemide, and AZD4144.	Drug: Rosuvastatin, Furosemide, and AZD4144 Part C; Participants will be administered a single oral dose of 10 mg Rosuvastatin, 1 mg Furosemide and a single dose of AZD4144 via IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs) (Part A and Part B)	To assess the safety and tolerability of AZD4144 following IV administration of single (Part A) and multiple (Part B) ascending doses in healthy participants.	Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3.
Area under plasma concentration-time curve from time 0 to infinity (AUCinf) (Part C)	To evaluate the effect of AZD4144 on the PK of rosuvastatin and furosemide in healthy participants.	Treatment period 1: Day 1 to 3; Treatment period 2: Day 10 to 12.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) (Part C)	To evaluate the effect of AZD4144 on the PK of rosuvastatin and furosemide in healthy participants.	Treatment period 1: Day 1 to 3; Treatment period 2: Day 10 to 12.
Maximum observed drug concentration (Cmax) (Part C)	To evaluate the effect of AZD4144 on the PK of rosuvastatin and furosemide in healthy participants.	Treatment period 1: Day 1 to 3; Treatment period 2: Day 10 to 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (Part A and Part B)	To characterize the PK of AZD4144 following IV administration of single (Part A) and multiple (Part B) ascending doses.	Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3
AUClast (Part A and Part B)	To characterize the PK of AZD4144 following IV administration of single (Part A) and multiple (Part B) ascending doses	Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3
AUCinf (Part A)	To characterize the PK of AZD4144 following IV administration of single (Part A) ascending doses.	Part A: Day 1 to Day 10+3
Area under concentration-time curve in the dosing interval (AUCτ) (Part B only)	To characterize the PK of AZD4144 following IV administration of multiple (Part B) ascending doses	Part B: Day 1 to Day 20+3
Renal clearance of drug from plasma (CLR) (Part A and Part B)	To characterize the PK of AZD4144 following IV administration of single (Part A) and multiple (Part B) ascending doses.	Part A: Day 1 to 3; Part B: Day 1, 12 and 20+3
PD analysis: Levels of disease-specific biomarkers (Part A and Part B)	To assess the effect of AZD4144 on levels of disease-specific biomarkers. (Part A and Part B)	Part A: Day -1 to 4; Part B: Day -1 to Day 1, Day 12 to Day 15
Number of participants with adverse events (AEs) (Part C)	To assess the safety and tolerability of AZD4144 in combination with rosuvastatin and furosemide in healthy participants.	Part C: Day 1 to Day 20+3

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Actual): June 11, 2025
• Study Completion (Actual): June 11, 2025

Study Registration Dates

• First Submitted: July 1, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Single ascending dose (SAD); Multiple ascending dose (MAD); Drug-drug interaction (DDI); Pharmacokinetic (PK); Pharmacodynamic (PD)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Membrane Transport Modulators; Diuretics; Natriuretic Agents; Sodium Potassium Chloride Symporter Inhibitors; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Furosemide
• Other Study ID Numbers: D9440C00002

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