Clinical trial NCT06491550: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Pharmacokinetic (PK)
Pharmacodynamic (PD)
Drug-drug interaction (DDI)
Single ascending dose (SAD)
Multiple ascending dose (MAD)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-07-09
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Number of participants with adverse events (AEs) (Part A and Part B)
timeFrame: Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3.
measure: Area under plasma concentration-time curve from time 0 to infinity (AUCinf) (Part C)
timeFrame: Treatment period 1: Day 1 to 3; Treatment period 2: Day 10 to 12.
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) (Part C)
timeFrame: Treatment period 1: Day 1 to 3; Treatment period 2: Day 10 to 12.
measure: Maximum observed drug concentration (Cmax) (Part C)
timeFrame: Treatment period 1: Day 1 to 3; Treatment period 2: Day 10 to 12.
Secondary outcomes:
measure: Cmax (Part A and Part B)
timeFrame: Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3
measure: AUClast (Part A and Part B)
timeFrame: Part A: Day 1 to Day 10+3; Part B: Day 1 to Day 20+3
measure: AUCinf (Part A)
timeFrame: Part A: Day 1 to Day 10+3
measure: Area under concentration-time curve in the dosing interval (AUCτ) (Part B only)
timeFrame: Part B: Day 1 to Day 20+3
measure: Renal clearance of drug from plasma (CLR) (Part A and Part B)
timeFrame: Part A: Day 1 to 3; Part B: Day 1, 12 and 20+3
measure: PD analysis: Levels of disease-specific biomarkers (Part A and Part B)
timeFrame: Part A: Day -1 to 4; Part B: Day -1 to Day 1, Day 12 to Day 15
measure: Number of participants with adverse events (AEs) (Part C)
timeFrame: Part C: Day 1 to Day 20+3
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
Study officials:
References: