Efficacy of Obicetrapib and Obicetrapib plus Ezetimibe in Reducing LDL-C in Patients with Type 2 Diabetes and/or Metabolic Syndrome
- Trial ID
- 2025-521936-12-00
- Protocol
- OBEZ-303
- Sponsor
- NewAmsterdam Pharma B.V.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of Obicetrapib 10 mg + Ezetimibe 10 mg fixed-dose combination (FDC) therapy and Obicetrapib 10 mg monotherapy on low-density lipoprotein cholesterol (LDL-C) in participants with Type 2 Diabetes and/or Metabolic Syndrome receiving guideline-recommended lipid-lowering therapy. 5
Secondary objectives include the assessment of the following:
- Effect on non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), ApoA1, and lipoprotein(a) (Lp(a)).
- Proportion of participants achieving predefined LDL-C targets.
- Lipoprotein and subfraction particle concentrations, particle sizes via nuclear magnetic resonance (NMR) spectroscopy, and small dense LDL cholesterol (sdLDL-C).
- Mean trough plasma levels of Obicetrapib.
- Effect of FDC therapy on various lipid parameters and LDL-C targets during an open-label extension.
Participants
This study involves 182 participants consisting of male and female adults. The study population includes individuals diagnosed with Type 2 diabetes mellitus or metabolic syndrome. Eligible participants must have low-density lipoprotein cholesterol levels ≥70 mg/dL and triglycerides between 150 mg/dL and 400 mg/dL. Participants must be on stable, guideline-recommended lipid-lowering therapy, such as a statin, bempedoic acid, or PCSK9 inhibitor. Additionally, an estimated glomerular filtration rate of ≥15 mL/min/1.73 m2 is required.
Plans and Procedures
This Phase 3, placebo-controlled, double-blind, randomized study is designed to evaluate the efficacy of Obicetrapib 10 mg and Ezetimibe 10 mg fixed-dose combination (FDC) or Obicetrapib 10 mg monotherapy in participants with Type 2 Diabetes and/or Metabolic Syndrome. The primary objective is to assess the effect of these treatments on low-density lipoprotein cholesterol (LDL-C) levels when added to guideline-recommended lipid-lowering therapy. The study procedures begin with a screening visit to assess eligibility based on clinical criteria, such as fasting serum LDL-C and triglyceride levels, and stable use of existing lipid-modifying medications. Following screening, participants are randomized to receive either the active test products or a matching placebo. The primary efficacy endpoint is measured by the percent change from baseline to Day 84. The total trial duration, including recruitment and completion, is estimated to extend from April 2026 to September 2027.
Treatment
Obicetrapib is administered as a 10 mg tablet via oral use. This investigational medicinal product is evaluated as a monotherapy.
The fixed-dose combination (FDC) of Obicetrapib and ezetimibe is administered as a 10 mg tablet via oral use. This treatment is utilized in conjunction with guideline-recommended lipid-lowering therapy.
A placebo matching the Obicetrapib 10 mg tablet is used as a comparator treatment. A second placebo matching the Obicetrapib 10 mg and ezetimibe 10 mg fixed-dose combination is also utilized in the study protocol.
Efficacy
The primary efficacy endpoint is the percent change from baseline to Day 84 in low-density lipoprotein cholesterol (LDL-C). This is evaluated by comparing the 10 mg obicetrapib and 10 mg ezetimibe fixed-dose combination (FDC) treatment group and the 10 mg obicetrapib monotherapy group against a placebo group. Additionally, the difference in percent change from baseline to Day 84 in LDL-C between the FDC group and the monotherapy group is assessed.
Secondary efficacy parameters include the percent change from baseline to Day 84 in the following:
- non-HDL-C
- high-density lipoprotein cholesterol (HDL-C)
- apolipoprotein B (ApoB)
- apolipoprotein A1 (ApoA1)
- lipoprotein (a) (Lp(a))
Exploratory endpoints involve assessing the proportion of participants reaching specific LDL-C thresholds at Day 84, specifically levels below 100 mg/dL, 70 mg/dL, and 55 mg/dL. Further exploratory assessments include the percent change from baseline to Day 84 in small dense LDL cholesterol (sdLDL-C), glycated hemoglobin (HbA1c), and very low-density lipoprotein cholesterol (VLDL-C). The percent change in particle numbers and size is determined via NMR analysis. In the open-label extension, efficacy is assessed at every visit for percent change from baseline in LDL-C, non-HDL-C, ApoB, total cholesterol, triglycerides, HDL-C, and Lp(a), alongside the proportion of participants achieving predefined LDL-C targets.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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.
- 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.
- Have a fasting serum LDL-C at Screening (Visit 1) ≥70 mg/dL (≥1.8 mmol/L)
- Have fasting TG ≥150 mg/dL (≥1.7 mmol/L) and <400 mg/dL (<4.5 mmol/L) at Screening (Visit 1)
- 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).
- 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
- Have current or any previous history of New York Heart Association class III or IV heart failure or left ventricular ejection fraction <30%
- Have been hospitalized for heart failure within 5 years prior to Screening (Visit 1)
- 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
- Have a formal diagnosis of homozygous familial hypercholesterolemia
- 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)
- Have an HbA1c ≥10.0%(≥0.100 hemoglobin fraction) at Screening (Visit 1)
- Have thyroid-stimulating hormone >1.5 × ULN at Screening (Visit 1)
- Have creatine kinase (CK) >5 × ULN at Screening (Visit 1)
- 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])
- 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
- 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
- Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1)
- Are taking ezetimibe or have taken ezetimibe within 14 days of Screening (Visit 1)
- 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
- 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
- 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])
- Have planned use of other investigational products or devices during the course of the study
- Have participated in any clinical study evaluating obicetrapib
- Have a known allergy or hypersensitivity to the study drugs, placebo, or any of the excipients in the study drugs or placebo; or
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Recruiting | 01 Apr 2026 | 48 |
 The Netherlands | Recruiting | 01 Apr 2026 | — |
 Slovakia | Recruiting | 01 Apr 2026 | 49 |
| Netherlands | — | — | 21 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo matching Obicetrapib 10 mg + ezetimibe 10 mg fixed dose combination (FDC) tablets | Placebo | N/A | ORAL USE | — | — | N/A |
Obicetrapib | Test | TABLET | ORAL USE | 10 | 84 | PRD13042033 |
Obicetrapib 10 mg + ezetimibe 10 mg fixed dose combinationFDC | Test | TABLET | ORAL USE | 10 | 365 | PRD11167913 |
Placebo matching Obicetrapib 10 mg tablets | Placebo | N/A | — | — | — | N/A |