EZETIMIBE; OBICETRAPIB for Type 2 diabetes|Metabolic syndrome|Elevated LDL-cholesterol

Inclusion criteria

• {"criterion_text":"- 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\n- Are male or female and ≥18 years of age at Screening (Visit 1); o Females may be enrolled if all 3 of the following criteria are met:  They are not pregnant;  They are not breastfeeding; and  They do not plan on becoming pregnant during the study. o Female participants of childbearing potential and male participants whose partners are of childbearing potential must comply with the contraceptive requirements outlined in Appendix D.\n- Have a known diagnosis of type 2 diabetes mellitus based on the American Diabetes Association criteria (see Appendix C) for at least 6 months prior to Screening (Visit 1); OR Have metabolic syndrome, defined as: o Fasting TG ≥150 mg/dL (≥1.7 mmol/L) and <400 mg/dL (<4.5 mmol/L) at Screening (Visit 1) (Inclusion Criterion 5); and o 2 or more of the following:  Fasting plasma glucose concentration ≥100 mg/dl (≥5.6 mmol/L) or HbA1c >5.7% or are receiving pharmacologic therapy for elevated fasting glucose levels;  HDL-C <40 mg/dL (<1.0 mmol/L) for men; <50 mg/dL (<1.3 mmol/L) for women;  Waist circumference ≥102 cm (men) or ≥88 cm (women) (≥90 cm [men] or ≥80 cm [women] for Asians and participants of Asian descent);  Hypertension, defined as persistent elevated systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg, or are receiving pharmacologic therapy for hypertension; or  Microalbuminuria, defined as a urine albumin-creatinine ratio ≥30 mg/g.\n- Have a fasting serum LDL-C at Screening (Visit 1) ≥70 mg/dL (≥1.8 mmol/L)\n- Have fasting TG ≥150 mg/dL (≥1.7 mmol/L) and <400 mg/dL (<4.5 mmol/L) at Screening (Visit 1)\n- Are on stable guideline-recommended lipid-lowering therapy, defined as at least one of the following therapies: o A statin for at least 8 weeks prior to Screening (Visit 1) o Bempedoic acid for at least 8 weeks prior to Screening (Visit 1); or o A PCSK9-targeted therapy alone or in combination with other lipid-modifying therapy for at least 4 doses prior to Screening (Visit 1).\n- Have an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation at Screening (Visit 1)."}

Exclusion criteria

• {"criterion_text":"- Have current or any previous history of New York Heart Association class III or IV heart failure or left ventricular ejection fraction <30%\n- Have a known history of alcohol and/or drug abuse within 5 years prior to Randomization (Visit 2 [Day 1]); as assessed by the Investigator\n- Have received treatment with other investigational products or devices within 30 days of Screening (Visit 1) or 5 half-lives of the previous investigational product, whichever is longer\n- Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1)\n- Are taking ezetimibe or have taken ezetimibe within 14 days of Screening (Visit 1)\n- Have had weight loss surgery (eg, sleeve gastrectomy, Roux-en-Y) within the last 12 months prior to Screening (Visit 1) or have plans for weight loss surgery during the study period\n- Are currently participating or have recently participated (within the 3 months prior to Randomization [Visit 2 (Day 1)]) in a weight loss program or are planning on participating in a medical or surgical weight loss program during the study\n- Have had a recent significant change in body weight, defined as a >5% change in body weight in the 3 months prior to Randomization (Visit 2 [Day 1])\n- Have planned use of other investigational products or devices during the course of the study\n- Have participated in any clinical study evaluating obicetrapib\n- Have a known allergy or hypersensitivity to the study drugs, placebo, or any of the excipients in the study drugs or placebo; or\n- Have been hospitalized for heart failure within 5 years prior to Screening (Visit 1)\n- 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: o Are unable to communicate or to cooperate with the Investigator; o 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); o 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); o 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 o Are directly involved in the conduct of the study\n- Have uncontrolled severe hypertension, defined as either systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at both Screening (Visit 1) and Randomization (Visit 2 [Day 1]) taken as the average of triplicate measurements\n- Have a formal diagnosis of homozygous familial hypercholesterolemia\n- Have active liver disease, defined as any known current infectious, neoplastic, or metabolic pathology of the liver, Child-Pugh score of 7 to 9 (Class B) or 10 to 15 (Class C);, unexplained elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN); or total bilirubin >2 × ULN at Screening (Visit 1)\n- Have an HbA1c ≥10.0%(≥0.100 hemoglobin fraction) at Screening (Visit 1)\n- Have thyroid-stimulating hormone >1.5 × ULN at Screening (Visit 1)\n- Have creatine kinase (CK) >5 × ULN at Screening (Visit 1)\n- 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 [Day 1])"}

Primary endpoints

• {"endpoint_text":"- The percent change from Baseline to Day 84 in LDL-C compared with placebo for the following treatment groups: • obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group; and • obicetrapib 10 mg monotherapy treatment group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in LDL-C compared with placebo; measured as percent change between baseline measurement and Day 84 LDL-C values."}
• {"endpoint_text":"- The percent change from Baseline to Day 84 in LDL-C for obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the obicetrapib 10 mg monotherapy treatment group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in LDL-C comparing obicetrapib+ezetimibe FDC vs obicetrapib monotherapy; measured as percent change between baseline and Day 84 LDL-C."}

Secondary endpoints

• {"endpoint_text":"- Percent change from Baseline to Day 84 in non-HDL-C for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in non-HDL-C; measured as percent change baseline to Day 84."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in HDL-C for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in HDL-C; measured as percent change baseline to Day 84."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in ApoB for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in apolipoprotein B (ApoB); measured as percent change baseline to Day 84."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in ApoA1 for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in apolipoprotein A1 (ApoA1); measured as percent change baseline to Day 84."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in non-HDL-C for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in non-HDL-C for obicetrapib monotherapy vs placebo."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in HDL-C for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in HDL-C for obicetrapib monotherapy vs placebo."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in ApoB for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in ApoB for obicetrapib monotherapy vs placebo."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in ApoA1 for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in ApoA1 for obicetrapib monotherapy vs placebo."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in lipoprotein (a) (Lp[a]) for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in Lp(a) for obicetrapib+ezetimibe FDC vs placebo."}
• {"endpoint_text":"- Percent change from Baseline to Day 84 in Lp(a) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in Lp(a) for obicetrapib monotherapy vs placebo."}
• {"endpoint_text":"- Exploratory: Proportion of participants at Day 84 that achieve LDL-C <100 mg/dL (<2.6 mmol/L), LDL--C <70 mg/dL (<1.8 mmol/L), and LDL-C <55 mg/dL (<1.4 mmol/L) for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Proportion of participants at Day 84 achieving specified LDL-C thresholds; compared between treatment groups and placebo."}
• {"endpoint_text":"- Exploratory: Percent change from Baseline to Day 84 in particle numbers and size, as measured by NMR analysis, of LDL-C, HDL-C, and VLDL-C for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in particle numbers and sizes measured by NMR for LDL-C, HDL-C, VLDL-C; comparison by treatment group."}
• {"endpoint_text":"- Exploratory: Percent change from Baseline to Day 84 in sdLDL-C for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in small dense LDL-C (sdLDL-C); comparison by treatment group."}
• {"endpoint_text":"- Exploratory: Percent change from Baseline to Day 84 in HbA1c for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change from Baseline to Day 84 in HbA1c; comparison by treatment group."}
• {"endpoint_text":"- OLE exploratory efficacy endpoints are assessed from Baseline at every visit for the following parameters: • Percent change from Baseline over time in LDL-C; • Proportion of participants that achieve LDL-C <100 mg/dL (<2.6 mmol/L), LDL-C <70 mg/dL (<1.8 mmol/L), and LDL-C <55 mg/dL (<1.4 mmol/L); • Percent change from Baseline over time in non-HDL-C, ApoB, total cholesterol, triglycerides, HDL-C, Lp(a)","definition_or_measurement_approach":"Open-label extension exploratory endpoints assessed at each visit vs baseline for LDL-C and other lipid parameters; includes percent change over time and proportions achieving LDL-C targets."}

Other endpoints

• {"endpoint_text":"- Exploratory: Proportion of participants at Day 84 that achieve LDL-C <100 mg/dL (<2.6 mmol/L), LDL--C <70 mg/dL (<1.8 mmol/L), and LDL-C <55 mg/dL (<1.4 mmol/L) for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Proportion achieving predefined LDL-C targets at Day 84; comparison across treatment groups and placebo."}
• {"endpoint_text":"- Exploratory: Percent change from Baseline to Day 84 in particle numbers and size, as measured by NMR analysis, of LDL-C, HDL-C, and VLDL-C for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"NMR-measured particle number and size percent change from baseline to Day 84."}
• {"endpoint_text":"- Exploratory: Percent change from Baseline to Day 84 in sdLDL-C for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change in small dense LDL-C from baseline to Day 84."}
• {"endpoint_text":"- Exploratory: Percent change from Baseline to Day 84 in HbA1c for the obicetrapib 10 mg + ezetimibe 10 mg FDC treatment group compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group","definition_or_measurement_approach":"Percent change in HbA1c from baseline to Day 84."}
• {"endpoint_text":"- OLE exploratory efficacy endpoints are assessed from Baseline at every visit for the following parameters: • Percent change from Baseline over time in LDL-C; • Proportion of participants that achieve LDL-C <100 mg/dL (<2.6 mmol/L), LDL-C <70 mg/dL (<1.8 mmol/L), and LDL-C <55 mg/dL (<1.4 mmol/L); • Percent change from Baseline over time in non-HDL-C, ApoB, total cholesterol, triglycerides, HDL-C, Lp(a)","definition_or_measurement_approach":"OLE endpoints assessed longitudinally vs baseline for LDL-C and a range of lipid parameters."}

Netherlands

Earliest CTIS Part Ii Submission Date

06-03-2026

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

25

Number Of Sites

5

Number Of Participants

21

Slovakia

Earliest CTIS Part Ii Submission Date

09-03-2026

Latest Decision Or Authorization Date

01-04-2026

Processing Time Days

23

Number Of Sites

8

Number Of Participants

49

Czechia

Earliest CTIS Part Ii Submission Date

23-03-2026

Latest Decision Or Authorization Date

31-03-2026

Processing Time Days

8

Number Of Sites

12

Number Of Participants

48

Primary sponsor

Full Name

NewAmsterdam Pharma B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

Medpace Inc.

Responsibilities

8

Name

Almac Clinical Services Limited

Responsibilities

14

Name

Fortrea Inc.

Responsibilities

1,10,11,12,2,5,6,9

Name

EndPoint Clinical Inc.

Responsibilities

3

Name

Medidata Solutions Inc.

Responsibilities

7

Third parties

• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"1,10,11,12,2,5,6,9","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Bioanalytical Laboratories","duties_or_roles":"4","organisation_type":"Health care"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EndPoint Clinical Inc.","duties_or_roles":"3","organisation_type":"Health care"}
• {"country":"United States","full_name":"LipoScience (Labcorp Global Research Services)","duties_or_roles":"4","organisation_type":"Industry"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}