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

NCT ID: NCT06491550

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-15
• Study Completion Date: 2025-06-11

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

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

Conditions

Healthy Participants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part A1-Cohort 1

Participants will receive one single ascending dose of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part A

Intervention Type: DRUG

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

Part A1- Cohort 2

Participants will receive one single ascending dose of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part A

Intervention Type: DRUG

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

Part A1-Cohort 3

Participants will receive one single ascending dose of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part A

Intervention Type: DRUG

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

Part A2-Japanese cohort 1

Participants will receive one single ascending dose of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part A

Intervention Type: DRUG

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

Part A2: Japanese Cohort 2

Participants will receive one single ascending dose of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part A

Intervention Type: DRUG

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

Part A3-Chinese Cohort

Participants will receive one single ascending dose of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part A

Intervention Type: DRUG

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

Part B1- Cohort 1

Participants will receive multiple ascending doses of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part B

Intervention Type: 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 2

Participants will receive multiple ascending doses of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part B

Intervention Type: 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 3

Participants will receive multiple ascending doses of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part B

Intervention Type: 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 B2- Japanese Cohort

Participants will receive multiple ascending doses of AZD4144.

Group Type: EXPERIMENTAL

AZD4144- Part B

Intervention Type: 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 C Cohort- Treatment C1

Participants will receive rosuvastatin and furosemide.

Group Type: EXPERIMENTAL

Rosuvastatin and Furosemide- Part C

Intervention Type: DRUG

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

Part C cohort- Treatment C2

Participants will receive rosuvastatin, furosemide, and AZD4144.

Group Type: EXPERIMENTAL

Rosuvastatin, Furosemide, and AZD4144 Part C

Intervention Type: 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 A1- Placebo

Participants will receive matching placebo.

Group Type: PLACEBO_COMPARATOR

Placebo- Part A

Intervention Type: DRUG

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

Part A2- Placebo

Participants will receive matching placebo.

Group Type: PLACEBO_COMPARATOR

Placebo- Part A

Intervention Type: DRUG

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

Part A3- Placebo

Participants will receive matching Placebo.

Group Type: PLACEBO_COMPARATOR

Placebo- Part A

Intervention Type: DRUG

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

Part B1- Placebo

Participants will receive matching Placebo.

Group Type: PLACEBO_COMPARATOR

Placebo- Part B

Intervention Type: 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 B2- Placebo

Participants will receive matching Placebo.

Group Type: PLACEBO_COMPARATOR

Placebo- Part B

Intervention Type: 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.

Interventions

AZD4144- Part A

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

Intervention Type: DRUG

Placebo- Part A

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Rosuvastatin and Furosemide- Part C

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

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Glendale, California, United States

Research Site

Brooklyn, Maryland, United States

Countries

United States

Other Identifiers

D9440C00002

Identifier Type: -

Identifier Source: org_study_id