The main aim of this study is to assess the effects of AZD0780 when added on top of ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
This is a randomized, single-blind, placebo-controlled study in healthy participants with elevated low-density lipoprotein-cholesterol (LDL-C). This study will assess the pharmacokinetic (PK), safety, tolerability, and efficacy of AZD0780 in combination with ezetimibe, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid. Participants will be randomized to receive either AZD0780 or placebo (to be administered with ezetimibe, ezetimibe/rosuvastatin, or ezetimibe/bempedoic acid). The study will comprise: 1. A Screening Period of up to 28 days. 2. A Run-in Period of 28 days. 3. A Treatment Period of 28 days. 4. Two Follow-up Visits, one and two weeks after the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
81
AZD0780 tablet will be administered orally.
Ezetimibe tablet will be administered orally.
Rosuvastatin tablet will be administered orally.
Research Site
Glendale, California, United States
Research Site
Brooklyn, Maryland, United States
Research Site
Harrow, United Kingdom
Change from baseline in direct Low-density Lipsprotein Cholesterol (LDL-C)
To evaluate the effect of AZD0780 on LDL-C levels versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Number of participants with adverse events
The safety and tolerability of AZD0780 when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid will be assessed.
Time frame: From screening (Day -56 to -29) to 14 Weeks
Plasma concentration of AZD0780
To further characterize AZD0780 pharmacokinetics (PK) in plasma.
Time frame: From Day 1 to Day 42
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
To further characterize AZD0780 PK in plasma.
Time frame: From Day 1 to Day 42
Area under concentration-time curve in the dosing interval (AUCtau) (Day 15)
To further characterize AZD0780 PK in plasma.
Time frame: From Day 1 to Day 42
Maximum observed drug concentration (Cmax)
To further characterize AZD0780 PK in plasma.
Time frame: From Day 1 to Day 42
Time to reach maximum observed concentration (tmax)
To further characterize AZD0780 PK in plasma.
Time frame: From Day 1 to Day 42
Change from baseline in LDL-C ultra
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Bempedoic Acid tablet will be administered orally.
Placebo will be administered orally.
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Change from baseline in LDL-C Friedewald
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Change from baseline in total cholesterol
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Change from baseline in non- HDL-C (high-density lipoprotein-cholesterol)
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Change from baseline in HDL-C
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Change from baseline in triglycerides
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Change from baseline in in Lipoprotein A [Lp(a)]
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4
Change from baseline in Apolipoprotein B (ApoB)
To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.
Time frame: Week 4