A trial to test the effect of obicetrapib/ezetimibe on coronary plaque characteristics on coronary computerized tomography angiography in people with atherosclerotic cardiovasculardisease
- Conditions
- Atherosclerotic Cardiovascular DiseaseTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- CTIS2023-508475-36-00
- Lead Sponsor
- ewAmsterdam Pharma B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 362
1. Are willing and able to give written informed consent before initiation of any study-related procedures and willing to comply with all required study procedures, 2. Participant must have body mass index within the range 18 to 40 kg/m2, inclusive at Screening (Visit 1), 3. Are male or female and =45 years of age at Screening (Visit 1) A. Females may be enrolled if all 3 of the following criteria are met: i. They are not pregnant ii. They are not breastfeeding; and iii. They do not plan on becoming pregnant during the study B. Females of childbearing potential must have a negative urine pregnancy test at Screening (Visit 1) Note: Females are not considered to be of childbearing potential if they meet 1 of the following criteria, as documented by the investigator: i. They have had a hysterectomy or tubal ligation at a minimum of 1 cycle prior to signing the ICF; or ii. They are postmenopausal, defined as =1 year since their last menstrual period for females =55 years of age or =1 year since their last menstrual period and have a follicle-stimulating hormone level in the postmenopausal range at Screening (Visit 1) for females <55 years of age C. Females of childbearing potential must agree to use an effective method of avoiding pregnancy from Screening (Visit 1) until 35 days after the last dose of study drug. Males whose partners are of childbearing potential must agree to use an effective method of avoiding pregnancy from Screening (Visit 1) until 35 days after the last dose of study drug. Effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, and barrier methods) or a sterile sexual partner for at least 3 months prior to study drug administration, 4. Have ASCVD as evidenced by having AT LEAST ONE feature in Group A AND/OR Group B below: A. Imaging evidence of vascular disease This is defined as having one of the following on prior clinically indicated vascular imaging: i. Angiographic evidence of coronary artery disease (invasive or CCTA) with a visual diameter stenosis <50% in at least one major epicardial coronary artery ii. Angiographic evidence of coronary artery disease with a visual diameter stenosis >50% in at least one major epicardial coronary artery but fractional flow reserve >0.8 (invasive or CCTA derived) iii. Carotid artery stenosis >50% B. Having established clinically manifest ASCVD This is defined as having one of the following: i. History of myocardial infarction (MI) ii. History of ischemic stroke iii. Previous percutaneous coronary intervention (PCI) iv. Previous carotid artery revascularization v. Documentation of a resting ankle-brachial index =0.85 vi. Previous revascularization of an iliac, femoral, or popliteal artery or lower extremity amputation due to peripheral artery disease, 5. Has evidence by CCTA of evaluable non-calcified plaque (as determined by a central study core imaging laboratory) of at least 75 mm3 in the major epicardial coronary arteries, 6. Are on lipid-modifying therapy as an adjunct to a lipid-lowering diet and other lifestyle modifications, defined as ANY ONE of the below: A. A statin at a maximally tolerated stable dose i. A participant’s maximally tolerated stable statin dose will be determined by the investigator using his/her medical judgment and available sources, including the participant’s self-reported h
1. Have current or any previous history of New York Heart Association class III or IV heart failure or left ventricular ejection fraction <30%, 10. Have a history of a malignancy that required surgery (excluding local and wide-local excision), radiation therapy, and/or systemic therapy during the 3 years prior to Randomization (Visit 2), 11. Have a known history of alcohol and/or drug abuse within 5 years prior to Randomization (Visit 2), 12. Have received treatment with other investigational products (IPs) or devices within 30 days of Screening (Visit 1) or 5 half-lives of the previous IP, whichever is longer. Note: Participants who have received treatment for coronavirus disease 2019 with standard of care and/or emergency use authorization medications, including vaccinations and boosters, within 30 days of Screening (Visit 1) or 5 half-lives of the previous IP will be permitted., 13. Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1), 14. Are taking ezetimibe or have taken ezetimibe within 30 days of Screening (Visit 1), 15. Have planned use of other IPs or investigational devices during the study, 16. Have participated in any clinical study evaluating obicetrapib, 17. Have a known allergy or hypersensitivity to the ezetimibe or cholesteryl ester transfer protein inhibitors, or any of the excipients contained within the FDC of ezetimibe and obicetrapib (ie, the IP) or the placebo, 18. Have any participant condition that, according to the investigator, could interfere with the conduct of the study, such as, but not limited to, the following: • Are unable to communicate or to cooperate with the investigator • Are unable to understand the protocol requirements, instructions and study-related restrictions, and the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency) • Are unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study) • At the discretion of the clinician or the learned opinion of the trial participant, an inability of the participant to comfortably lie flat AND still for at least 15 minutes • Have any medical or surgical condition which, in the opinion of the investigator, would put the participant at increased risk from participating in the study; or • Are directly involved in the conduct of the study, 19. Participants with any of the following contraindications to CCTA: a. Are unable to communicate or to cooperate with the investigator b. History of contrast-induced nephropathy c. Allergy to iodinated contrast d. Contraindication to nitroglycerin e. Rapid heart rate that is uncontrolled by medical therapy f. Persistent or permanent atrial fibrillation g. Inability to hold breath for at least 6 seconds h. Any known contraindications to CCTA per local standards., 2. Have had any of the following clinical events within 3 months prior to Screening (Visit 1): • MI • Stroke • Non-elective coronary revascularization, 3. Have uncontrolled severe hypertension, defined as either systolic blood pressure =160 mmHg or diastolic blood pressure =100 mmHg prior to randomization, taken as the average of triplicate measurements. One triplicate retest (repeat of all 3) will be allowed during the same visit, at which point if the retest result is no longer exclusiona
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method