A Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 With Ezetimibe Combinations in Healthy Adults With Elevated LDL-C.
- Conditions
- Interventions
- Registration Number
- NCT06742853
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
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.
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Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 120
- Signed the informed consent form before any study-related procedure.
- All females must have a negative serum pregnancy test at the Screening Visit and on admission to the Clinical Unit
- Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria: postmenopausal or surgically sterilized females.
- Have a Body Mass Index (BMI) > 18 kg/m² and weigh at least 50 kg.
- Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
- Fasting LDL-C > 100 mg/dL but < 190 mg/dL (> 2.6 mmol/L but < 4.9 mmol/L for London EPCU) at the Screening Visit.
- Fasting triglycerides < 400 mg/dL (or < 10.3 mmol/L for London EPCU) at the Screening Visit.
- History of any clinically important disease or disorder.
- History 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 within 4 weeks of the first administration of study intervention.
- Any laboratory values with specific deviations in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBL), estimated glomerular filtration rate, or hemoglobin at the Screening Visit or on Admission
- Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results other than those described under exclusion criterion number 4, at Screening and/or Admission to the Clinical Unit
- Any positive result on Screening for serum HBsAg, hepatitis B core antibody or human immunodeficiency virus.
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD0780, ezetimibe, rosuvastatin, and bempedoic acid.
- Treatment with any lipid-lowering therapy or AZD0780 within the 3 months prior to Screening.
- Treatment with drugs for reduction or inhibition of Proprotein convertase subtilisin/kexin type 9 (PCSK9) within the last 12 months prior to Screening (approved or investigational and apart from AZD0780).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rosuvastatin + Ezetimibe + Placebo Ezetimibe Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and placebo QD for 4 weeks. Rosuvastatin + Ezetimibe + Placebo Rosuvastatin Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and placebo QD for 4 weeks. Rosuvastatin + Ezetimibe + Placebo Placebo Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and placebo QD for 4 weeks. Bempedoic Acid + Ezetimibe + Placebo (Optional Cohort) Ezetimibe Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and placebo QD for 4 weeks. Bempedoic Acid + Ezetimibe + Placebo (Optional Cohort) Bempedoic Acid Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and placebo QD for 4 weeks. Bempedoic Acid + Ezetimibe + Placebo (Optional Cohort) Placebo Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and placebo QD for 4 weeks. Bempedoic Acid + Ezetimibe + AZD0780 (Optional Cohort) Bempedoic Acid Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks. Ezetimibe + Placebo Ezetimibe Participants will receive ezetimibe 10 mg and placebo QD for 4 weeks. Ezetimibe + AZD0780 AZD0780 Participants will receive ezetimibe 10 mg and AZD0780 once daily (QD) for 4 weeks. Ezetimibe + AZD0780 Ezetimibe Participants will receive ezetimibe 10 mg and AZD0780 once daily (QD) for 4 weeks. Rosuvastatin + Ezetimibe + AZD0780 AZD0780 Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks. Rosuvastatin + Ezetimibe + AZD0780 Ezetimibe Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks. Rosuvastatin + Ezetimibe + AZD0780 Rosuvastatin Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks. Bempedoic Acid + Ezetimibe + AZD0780 (Optional Cohort) AZD0780 Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks. Bempedoic Acid + Ezetimibe + AZD0780 (Optional Cohort) Ezetimibe Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks. Ezetimibe + Placebo Placebo Participants will receive ezetimibe 10 mg and placebo QD for 4 weeks.
- Primary Outcome Measures
Name Time Method Change from baseline in direct Low-density Lipsprotein Cholesterol (LDL-C) Week 4 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.
Number of participants with adverse events From screening (Day -56 to -29) to 14 Weeks The safety and tolerability of AZD0780 when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid will be assessed.
- Secondary Outcome Measures
Name Time Method Plasma concentration of AZD0780 From Day 1 to Day 42 To further characterize AZD0780 pharmacokinetics (PK) in plasma.
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast) From Day 1 to Day 42 To further characterize AZD0780 PK in plasma.
Area under concentration-time curve in the dosing interval (AUCtau) (Day 15) From Day 1 to Day 42 To further characterize AZD0780 PK in plasma.
Maximum observed drug concentration (Cmax) From Day 1 to Day 42 To further characterize AZD0780 PK in plasma.
Time to reach maximum observed concentration (tmax) From Day 1 to Day 42 To further characterize AZD0780 PK in plasma.
Change from baseline in LDL-C ultra Week 4 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.
Change from baseline in LDL-C Friedewald Week 4 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.
Change from baseline in total cholesterol Week 4 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.
Change from baseline in non- HDL-C (high-density lipoprotein-cholesterol) Week 4 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.
Change from baseline in HDL-C Week 4 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.
Change from baseline in triglycerides Week 4 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.
Change from baseline in in Lipoprotein A [Lp(a)] Week 4 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.
Change from baseline in Apolipoprotein B (ApoB) Week 4 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.