A Study to Evaluate the Effect of Obicetrapib and Ezetimibe Fixed-Dose Combination (FDC) or Obicetrapib on LDL-C in Participants With Type 2 Diabetes and/or Metabolic Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NewAmsterdam Pharma B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

24 Apr 2026 → ongoing

Decision date (initial)

2026-03-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

NewAmsterdam Pharma B.V.

External identifiers

EU CT number

2025-521936-12-00

WHO UTN

U1111-1330-6979

ClinicalTrials.gov

NCT07219602

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

The primary objective of this study is to evaluate the effect of obicetrapib 10 mg + ezetimibe 10 mg FDC therapy and obicetrapib 10 mg monotherapy on LDL-C.

Secondary objectives 6

1. To evaluate the effect of obicetrapib 10 mg + ezetimibe 10 mg FDC therapy and obicetrapib 10 mg monotherapy on non high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL C), apolipoprotein (Apo) B, ApoA1, and lipoprotein (a) (Lp[a])
2. Exploratory: To evaluate the effect of obicetrapib 10 mg + ezetimibe 10 mg FDC therapy and obicetrapib 10 mg monotherapy on the proportion of participants achieving predefined LDL-C targets
3. Exploratory: To evaluate the effect of obicetrapib 10 mg + ezetimibe 10 mg FDC therapy and obicetrapib 10 mg monotherapy on the proportion of participants achieving predefined LDL-C targets
4. Exploratory: To evaluate the effect of obicetrapib 10 mg + ezetimibe 10 mg FDC therapy and obicetrapib 10 mg monotherapy on lipoprotein and subfraction particle concentrations and particle sizes by nuclear magnetic resonance (NMR) spectroscopy and small dense LDL cholesterol (sdLDL-C)
5. Exploratory: To assess the mean trough plasma levels of obicetrapib after obicetrapib 10 mg + ezetimibe 10 mg FDC therapy and obicetrapib 10 mg monotherapy
6. For OLE exploratory objective of this study is to evaluate the effect of obicetrapib 10 mg + ezetimibe 10 mg FDC therapy on various lipid parameters and LDL-C targets

Conditions and MedDRA coding

Adults with Type 2 Diabetes and/or Metabolic Syndrome on guideline recommended lipid lowering therapy and elevated low-density lipoprotein cholesterol (LDL-C)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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. 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.
3. 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.
4. Have a fasting serum LDL-C at Screening (Visit 1) ≥70 mg/dL (≥1.8 mmol/L)
5. Have fasting TG ≥150 mg/dL (≥1.7 mmol/L) and <400 mg/dL (<4.5 mmol/L) at Screening (Visit 1)
6. 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).
7. 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 20

1. Have current or any previous history of New York Heart Association class III or IV heart failure or left ventricular ejection fraction <30%
2. Have been hospitalized for heart failure within 5 years prior to Screening (Visit 1)
3. 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
4. Have a formal diagnosis of homozygous familial hypercholesterolemia
5. 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)
6. Have an HbA1c ≥10.0%(≥0.100 hemoglobin fraction) at Screening (Visit 1)
7. Have thyroid-stimulating hormone >1.5 × ULN at Screening (Visit 1)
8. Have creatine kinase (CK) >5 × ULN at Screening (Visit 1)
9. 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])
10. 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
11. 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
12. Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1)
13. Are taking ezetimibe or have taken ezetimibe within 14 days of Screening (Visit 1)
14. 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
15. 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
16. 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])
17. Have planned use of other investigational products or devices during the course of the study
18. Have participated in any clinical study evaluating obicetrapib
19. Have a known allergy or hypersensitivity to the study drugs, placebo, or any of the excipients in the study drugs or placebo; or
20. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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
2. 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

Secondary endpoints 15

1. 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
2. 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
3. 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
4. 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
5. Percent change from Baseline to Day 84 in non-HDL-C for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
6. Percent change from Baseline to Day 84 in HDL-C for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
7. Percent change from Baseline to Day 84 in ApoB for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
8. Percent change from Baseline to Day 84 in ApoA1 for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
9. 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
10. Percent change from Baseline to Day 84 in Lp(a) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group
11. 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
12. 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
13. 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
14. 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
15. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NewAmsterdam Pharma B.V.

Sponsor organisation

NewAmsterdam Pharma B.V.

Address

Gooimeer 2/35

City

Naarden

Postcode

1411 DC

Country

Netherlands

Scientific contact point

Organisation

NewAmsterdam Pharma B.V.

Contact name

Marc Ditmarsch

Public contact point

Organisation

NewAmsterdam Pharma B.V.

Contact name

-

Third parties 9

Locations

3 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications