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

NCT06491550 | Completed Phase 1 FDA Drug

• 1 other identifier: D9440C00002
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Healthy Participants

Keywords

Pharmacokinetic (PK); Pharmacodynamic (PD); Drug-drug interaction (DDI); Single ascending dose (SAD); Multiple ascending dose (MAD)

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• Cmax (Part A and Part B)

  Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3

• AUClast (Part A and Part B)

  Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3

• AUCinf (Part A)

  Part A: Day 1 to Day 10+3

• Area under concentration-time curve in the dosing interval (AUCτ) (Part B only)

  Part B: Day 1 to Day 20+3

• Renal clearance of drug from plasma (CLR) (Part A and Part B)

  Part A: Day 1 to 3; Part B: Day 1, 12 and 20+3

Study Arms (17)

Part A1-Cohort 1

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144- Part A

Part A1- Cohort 2

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144- Part A

Part A1-Cohort 3

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144- Part A

Part A2-Japanese cohort 1

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144- Part A

Part A2: Japanese Cohort 2

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144- Part A

Part A3-Chinese Cohort

EXPERIMENTAL

Participants will receive one single ascending dose of AZD4144.

Drug: AZD4144- Part A

Part B1- Cohort 1

EXPERIMENTAL

Participants will receive multiple ascending doses of AZD4144.

Drug: AZD4144- Part B

Part B1- Cohort 2

EXPERIMENTAL

Participants will receive multiple ascending doses of AZD4144.

Drug: AZD4144- Part B

Part B1- Cohort 3

EXPERIMENTAL

Participants will receive multiple ascending doses of AZD4144.

Drug: AZD4144- Part B

Part B2- Japanese Cohort

EXPERIMENTAL

Participants will receive multiple ascending doses of AZD4144.

Drug: AZD4144- Part B

Part C Cohort- Treatment C1

EXPERIMENTAL

Participants will receive rosuvastatin and furosemide.

Drug: Rosuvastatin and Furosemide- Part C

Part C cohort- Treatment C2

EXPERIMENTAL

Participants will receive rosuvastatin, furosemide, and AZD4144.

Drug: Rosuvastatin, Furosemide, and AZD4144 Part C

Part A1- Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo.

Drug: Placebo- Part A

Part A2- Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo.

Drug: Placebo- Part A

Part A3- Placebo

PLACEBO COMPARATOR

Participants will receive matching Placebo.

Drug: Placebo- Part A

Part B1- Placebo

PLACEBO COMPARATOR

Participants will receive matching Placebo.

Drug: Placebo- Part B

Part B2- Placebo

PLACEBO COMPARATOR

Participants will receive matching Placebo.

Drug: Placebo- Part B

Interventions

AZD4144- Part A DRUG

Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.

Part A1- Cohort 2; Part A1-Cohort 1; Part A1-Cohort 3; Part A2-Japanese cohort 1; Part A2: Japanese Cohort 2; Part A3-Chinese Cohort

Placebo- Part A DRUG

Part A: Participants will be administered a single dose of placebo on Day 1 via IV infusion.

Part A1- Placebo; Part A2- Placebo; Part A3- Placebo

AZD4144- Part B DRUG

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.

Part B1- Cohort 1; Part B1- Cohort 2; Part B1- Cohort 3; Part B2- Japanese Cohort

Placebo- Part B DRUG

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.

Part B1- Placebo; Part B2- Placebo

Rosuvastatin and Furosemide- Part C DRUG

Participants will be administered a single oral dose of 10 mg Rosuvastatin and 1 mg Furosemide.

Part C Cohort- Treatment C1

Rosuvastatin, Furosemide, and AZD4144 Part C DRUG

Participants will be administered a single oral dose of 10 mg Rosuvastatin, 1 mg Furosemide and a single dose of AZD4144 via IV infusion.

Part C cohort- Treatment C2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Glendale, California, 91206, United States

Location

Research Site

Brooklyn, Maryland, 21225, United States

Location

MeSH Terms

Interventions

Rosuvastatin Calcium; Furosemide

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfanilamides; Aniline Compounds; Amines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2024
• First Posted: July 9, 2024
• Study Start: July 15, 2024
• Primary Completion: June 11, 2025
• Study Completion: June 11, 2025
• Last Updated: July 4, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (2)