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
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
91
Part A: Participants will be administered a single dose of AZD4144 on Day 1 via Intravenous (IV) infusion.
Part A: Participants will be administered a single dose of placebo on Day 1 via IV infusion.
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 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.
Participants will be administered a single oral dose of 10 mg Rosuvastatin and 1 mg Furosemide.
Participants will be administered a single oral dose of 10 mg Rosuvastatin, 1 mg Furosemide and a single dose of AZD4144 via IV infusion.
Research Site
Glendale, California, United States
Research Site
Brooklyn, Maryland, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Treatment period 1: Day 1 to 3; Treatment period 2: Day 10 to 12.
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.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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)
Time frame: 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.
Time frame: Part C: Day 1 to Day 20+3
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