Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies

NCT06005597 | Completed Phase 3 Results FDA Drug

• 1 other identifier: OBEZ-301
• Study Type: interventional
• Target: 407
• Locations: 1 country
• Sites: 45

Brief Summary

The study is a placebo-controlled, double-blind, randomized, phase 3 study in participants with heterozygous familial hypercholesterolemia (HeFH) and/or atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors to evaluate the efficacy, safety and tolerability of obicetrapib 10mg and ezetimibe 10mg fixed dose combination as an adjunct to diet and maximally tolerated lipid-lowering therapy.

Conditions

Dyslipidemias; Hypercholesterolemia; Familial Hypercholesterolemia; ASCVD; High Cholesterol

Keywords

obicetrapib; statin; LDL-C; cholesterol; atherosclerosis

Outcome Measures

Primary Outcomes (4)

• Effect of Fixed-Dose Combination (FDC) Compared to Placebo on LDL-C

  LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).

  84 Days

• Effect of Fixed Dose Combination (FDC) Compared to Ezetimibe Monotherapy on LDL-C

  LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the ezetimibe monotherapy 10 mg group. LDL-C level was measured by preparative ultracentrifugation (PUC).

  84 Days

• Effect of Fixed Dose Combination (FDC) Compared to Obicetrapib Monotherapy on LDL-C

  LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the obicetrapib monotherapy 10 mg group. LDL-C level was measured by preparative ultracentrifugation (PUC).

  84 Days

• Effect of Obicetrapib Monotherapy Compared to Placebo on LDL-C

  LS mean percent change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 84 in the obicetrapib 10 mg group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).

  84 Days

Secondary Outcomes (8)

• Effect of Fixed Dose Combination (FDC) Compared to Placebo on Non-HDL-C

  84 Days

• Effect of Fixed Dose Combination (FDC) Compared to Placebo on Apolipoprotein B (ApoB)

  84 Days

• Effect of Obicetrapib Monotherapy Compared to Placebo on Non-HDL-C

  84 Days

• Effect of Obicetrapib Monotherapy Compared to Placebo on Apolipoprotein B (ApoB)

  84 Days

• Effect of Fixed-Dose Combination (FDC) Compared to Ezetimibe Monotherapy on Non-HDL-C

  84 Days

Study Arms (4)

Combination Therapy

EXPERIMENTAL

once-daily obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination tablet, placebo tablet, placebo capsule

Combination Product: Combination Therapy; Other: Obicetrapib Placebo; Other: Ezetimibe Placebo

Monotherapy obicetrapib

EXPERIMENTAL

once-daily obicetrapib 10 mg, placebo tablet, placebo capsule

Drug: Monotherapy obicetrapib; Other: Combination Therapy placebo; Other: Ezetimibe Placebo

Monotherapy ezetimibe

ACTIVE COMPARATOR

once-daily ezetimibe 10 mg capsule, 2 placebo tablets

Drug: Monotherapy ezetimibe; Other: Combination Therapy placebo; Other: Obicetrapib Placebo

Placebo

PLACEBO COMPARATOR

once-daily placebo tablets (2), placebo capsule

Other: Combination Therapy placebo; Other: Obicetrapib Placebo; Other: Ezetimibe Placebo

Interventions

Combination Therapy COMBINATION_PRODUCT

tablet; 10mg obicetrapib and 10mg ezetimibe fixed does combination

Also known as: Cholesteryl ester transfer protein (CETP) inhibitor, obicetrapib, ezetimibe

Combination Therapy

Monotherapy obicetrapib DRUG

tablet; 10mg obicetrapib

Also known as: CETP inhibitor

Monotherapy obicetrapib

Monotherapy ezetimibe DRUG

capsule; 10mg ezetimibe

Monotherapy ezetimibe

Combination Therapy placebo OTHER

tablet; no active ingredient

Monotherapy ezetimibe; Monotherapy obicetrapib; Placebo

Obicetrapib Placebo OTHER

tablet; no active ingredient

Combination Therapy; Monotherapy ezetimibe; Placebo

Ezetimibe Placebo OTHER

capsule; no active ingredient

Combination Therapy; Monotherapy obicetrapib; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have underlying HeFH and/or a history of ASCVD or multiple ASCVD risk factors
• On maximally tolerated lipid-modifying therapy as an adjunct to a diet and lifestyle modifications
• LDL-C ≥ 70 mg/dL
• Triglycerides \< 500
• Estimated glomerular filtration rate ≥ 15 mL/min/1.73 m2

You may not qualify if:

• History of New York Heart Association (NYHA) class III or IV heart failure of left ventricular ejection fraction \<30%
• Hospitalized for heart failure within the last 5 years
• Myocardial infarction, stroke, non-elective coronary revascularization or hospitalization for unstable angina or chest pain in the last 3 months
• Uncontrolled severe hypertension
• Diagnosis of homozygous FH
• Liver disease
• HbA1c ≥ 10.0% or fasting glucose ≥ 270 mg/dL
• Thyroid-stimulating hormone \>1.5 x upper limit of normal (ULN)
• History of malignancy
• Creatinine kinase (CK) \>3 X ULN
• Alcohol abuse
• Treatment with investigational product
• Treatment with gemfibrozil or ezetimibe
• Previous participation in a trial evaluating obicetrapib
• Known allergy to study drugs, placebo or excipients in study drugs of placebo

Sponsors & Collaborators

• NewAmsterdam Pharma: lead

Study Sites (45)

East Valley Diabetes & Endocrinology

Gilbert, Arizona, 85297, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Centricity Research - Columbus

Columbus, Georgia, 31904, United States

Location

Center for Advanced Research and Education

Gainesville, Georgia, 30501, United States

Location

NSC Research

Johns Creek, Georgia, 30024, United States

Location

North Georgia Clinical Research

Woodstock, Georgia, 30189, United States

Location

Evanston Premier Healthcare Research LLC

Skokie, Illinois, 60077, United States

Location

Cardiovascular Research of Northwest Indiana, LLC

Munster, Indiana, 46321, United States

Location

Grace Research, LLC - Bossier City, LA

Bossier City, Louisiana, 71111, United States

Location

Horizon Research Group of Opelousas

Eunice, Louisiana, 70535, United States

Location

Maryland Cardiovascular Specialists

Baltimore, Maryland, 21229, United States

Location

TidalHealth Peninsula Regional, Inc.

Salisbury, Maryland, 21804, United States

Location

McClaren Bay Heart and Vascular

Bay City, Michigan, 49770, United States

Location

Northern Pines Health Center

Buckley, Michigan, 49620, United States

Location

Sparrow Clinical Research Institute

Lansing, Michigan, 48912, United States

Location

Oakland Medical Research Center

Troy, Michigan, 48085, United States

Location

CentraCare Heart & Vascular Center

Saint Cloud, Minnesota, 56303, United States

Location

North Mississippi Medical Center

Tupelo, Mississippi, 38801, United States

Location

St. Louis Heart and Vascular Cardiology

St Louis, Missouri, 63136, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63136, United States

Location

Triad Internal Medicine

Asheboro, North Carolina, 27203, United States

Location

Cary Research Group, LLC

Cary, North Carolina, 27518, United States

Location

Novant Health Clinical Research, LLC

Charlotte, North Carolina, 27701, United States

Location

Novant Health Heart and Vascular Institute

Charlotte, North Carolina, 28204, United States

Location

Lucas Research, Inc

Morehead City, North Carolina, 28557, United States

Location

Wilmington Health Associates

Wilmington, North Carolina, 28412, United States

Location

Metabolic and Atherosclerosis Research Center

Cincinnati, Ohio, 45227, United States

Location

Summit Research Group, LLC

Stow, Ohio, 44240, United States

Location

Capital Area Research

Camp Hill, Pennsylvania, 17074, United States

Location

Monument Health Clinical Research, a department of Monument Health Rapid City Hospital, Inc

Rapid City, South Dakota, 57701, United States

Location

Chattanooga Research & Medicine, PLLC

Chattanooga, Tennessee, 37404, United States

Location

Cardiovascular Research of Knoxville

Powell, Tennessee, 37849, United States

Location

PharmaTex Research, LLC

Amarillo, Texas, 79109, United States

Location

Amarillo Heart Clinical Research Institute, Inc

Amarillo, Texas, 79124, United States

Location

South Texas Clinical Research

Corpus Christi, Texas, 78404, United States

Location

Diabetes and Thyroid Center of Fort Worth

Fort Worth, Texas, 76132, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Juno Research, LLC - Medical Center Office

Houston, Texas, 77054, United States

Location

DM Clinical Research

Houston, Texas, 77375, United States

Location

Wellness Clinical Research Associates

McKinney, Texas, 75069, United States

Location

Northwest Houston Heart Center

Tomball, Texas, 77375, United States

Location

Alpine Research Organization, Inc.

Clinton, Utah, 84015, United States

Location

Spectrum Medical, Inc.

Danville, Virginia, 24541, United States

Location

Hampton Roads Center for Clinical Research

Suffolk, Virginia, 23435, United States

Location

Related Publications (1)

• Sarraju A, Brennan D, Hayden K, Stronczek A, Goldberg AC, Michos ED, McGuire DK, Mason D, Tercek G, Nicholls SJ, Kling D, Neild AL, Kastelein J, Davidson M, Ditmarsch M, Nissen SE. Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2025 May 17;405(10491):1757-1768. doi: 10.1016/S0140-6736(25)00721-4. Epub 2025 May 7.

  PMID: 40347969 RESULT

Related Links

• Study results paper

MeSH Terms

Conditions

Dyslipidemias; Hypercholesterolemia; Hyperlipoproteinemia Type II; Atherosclerosis

Interventions

Combined Modality Therapy; Cholesterol Ester Transfer Proteins; Ezetimibe

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperlipidemias; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Glycoproteins; Glycoconjugates; Carbohydrates; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Carrier Proteins; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: NewAmsterdam Pharma

study.director@newamsterdampharma.com

+1(305) 627-3081

Study Officials

• Marc Ditmarsch, MD

  NewAmsterdam Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: placebo tablets made to resemble active; placebo capsule made to resemble active
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-controlled, double blind, randomized

Study Record Dates

• First Submitted: August 15, 2023
• First Posted: August 22, 2023
• Study Start: March 1, 2024
• Primary Completion: September 25, 2024
• Study Completion: October 16, 2024
• Last Updated: October 8, 2025
• Results First Posted: October 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (45)