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

September 18, 2025 updated by: NewAmsterdam Pharma

A Placebo-Controlled, Double-Blind, Randomized, Phase 3 Study to Evaluate the Effect of Obicetrapib 10 mg and Ezetimibe 10 mg Fixed Dose Combination Daily on Top of Maximally Tolerated Lipid-Modifying Therapy in Participants With Heterozygous Familial Hypercholesterolemia (HeFH) and/or Atherosclerotic Cardiovascular Disease (ASCVD) or Multiple ASCVD Risk Factors

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will be 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 as an adjunct to diet and maximally tolerated lipid-lowering therapy. The screening period for this study will take up to 14 days. Afterwards patients will be randomized 1:1:1:1 to Obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination, obicetrapib 10 mg, ezetimibe 10 mg or placebo for a 84 day treatment period. After the treatment period, patients will have an end of study follow-up visit.

Study Type

Interventional

Enrollment (Actual)

407

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85297
        • East Valley Diabetes & Endocrinology
    • Florida
      • Jacksonville, Florida, United States, 32216
        • Jacksonville Center for Clinical Research
      • Port Orange, Florida, United States, 32127
        • Progressive Medical Research
    • Georgia
      • Columbus, Georgia, United States, 31904
        • Centricity Research - Columbus
      • Gainesville, Georgia, United States, 30501
        • Center for Advanced Research and Education
      • Johns Creek, Georgia, United States, 30024
        • Nsc Research
      • Woodstock, Georgia, United States, 30189
        • North Georgia Clinical Research
    • Illinois
      • Skokie, Illinois, United States, 60077
        • Evanston Premier Healthcare Research LLC
    • Indiana
      • Munster, Indiana, United States, 46321
        • Cardiovascular Research of Northwest Indiana, LLC
    • Louisiana
      • Bossier City, Louisiana, United States, 71111
        • Grace Research, LLC - Bossier City, LA
      • Eunice, Louisiana, United States, 70535
        • Horizon Research Group of Opelousas
    • Maryland
      • Baltimore, Maryland, United States, 21229
        • Maryland Cardiovascular Specialists
      • Salisbury, Maryland, United States, 21804
        • TidalHealth Peninsula Regional, Inc.
    • Michigan
      • Bay City, Michigan, United States, 49770
        • McClaren Bay Heart and Vascular
      • Buckley, Michigan, United States, 49620
        • Northern Pines Health Center
      • Lansing, Michigan, United States, 48912
        • Sparrow Clinical Research Institute
      • Troy, Michigan, United States, 48085
        • Oakland Medical Research Center
    • Minnesota
      • Saint Cloud, Minnesota, United States, 56303
        • CentraCare Heart & Vascular Center
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • North Mississippi Medical Center
    • Missouri
      • St Louis, Missouri, United States, 63136
        • St. Louis Heart and Vascular Cardiology
      • St Louis, Missouri, United States, 63136
        • Washington University School of Medicine
    • North Carolina
      • Asheboro, North Carolina, United States, 27203
        • Triad Internal Medicine
      • Cary, North Carolina, United States, 27518
        • Cary Research Group, LLC
      • Charlotte, North Carolina, United States, 28204
        • Novant Health Heart and Vascular Institute
      • Charlotte, North Carolina, United States, 27701
        • Novant Health Clinical Research, LLC
      • Morehead City, North Carolina, United States, 28557
        • Lucas Research, Inc
      • Wilmington, North Carolina, United States, 28412
        • Wilmington Health Associates
    • Ohio
      • Cincinnati, Ohio, United States, 45227
        • Metabolic and Atherosclerosis Research Center
      • Stow, Ohio, United States, 44240
        • Summit Research Group, LLC
    • Pennsylvania
      • Camp Hill, Pennsylvania, United States, 17074
        • Capital Area Research
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Monument Health Clinical Research, A Department of Monument Health Rapid City Hospital, Inc
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Chattanooga Research & Medicine, PLLC
      • Powell, Tennessee, United States, 37849
        • Cardiovascular Research of Knoxville
    • Texas
      • Amarillo, Texas, United States, 79109
        • PharmaTex Research, LLC
      • Amarillo, Texas, United States, 79124
        • Amarillo Heart Clinical Research Institute, Inc
      • Corpus Christi, Texas, United States, 78404
        • South Texas Clinical Research
      • Fort Worth, Texas, United States, 76132
        • Diabetes and Thyroid Center of Fort Worth
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Houston, Texas, United States, 77054
        • Juno Research, LLC - Medical Center Office
      • Houston, Texas, United States, 77375
        • DM Clinical Research
      • McKinney, Texas, United States, 75069
        • Wellness Clinical Research Associates
      • Tomball, Texas, United States, 77375
        • Northwest Houston Heart Center
    • Utah
      • Clinton, Utah, United States, 84015
        • Alpine Research Organization, Inc.
    • Virginia
      • Danville, Virginia, United States, 24541
        • Spectrum Medical, Inc.
      • Suffolk, Virginia, United States, 23435
        • Hampton Roads Center for Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Other condition that would interfere with the conduct of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination Therapy
once-daily obicetrapib 10 mg and ezetimibe 10 mg fixed dose combination tablet, placebo tablet, placebo capsule
Combination product: Combination Therapy
tablet; 10mg obicetrapib and 10mg ezetimibe fixed does combination
Other Names:
  • ezetimibe
  • Cholesteryl ester transfer protein (CETP) inhibitor
  • obicetrapib
Other: Obicetrapib Placebo
tablet; no active ingredient
Other: Ezetimibe Placebo
capsule; no active ingredient
Experimental: Monotherapy obicetrapib
once-daily obicetrapib 10 mg, placebo tablet, placebo capsule
Other: Ezetimibe Placebo
capsule; no active ingredient
Drug: Monotherapy obicetrapib
tablet; 10mg obicetrapib
Other Names:
  • CETP inhibitor
Other: Combination Therapy placebo
tablet; no active ingredient
Active Comparator: Monotherapy ezetimibe
once-daily ezetimibe 10 mg capsule, 2 placebo tablets
Other: Obicetrapib Placebo
tablet; no active ingredient
Other: Combination Therapy placebo
tablet; no active ingredient
Drug: Monotherapy ezetimibe
capsule; 10mg ezetimibe
Placebo Comparator: Placebo
once-daily placebo tablets (2), placebo capsule
Other: Obicetrapib Placebo
tablet; no active ingredient
Other: Ezetimibe Placebo
capsule; no active ingredient
Other: Combination Therapy placebo
tablet; no active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of Fixed-Dose Combination (FDC) Compared to Placebo on LDL-C
Time Frame: 84 Days
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
Time Frame: 84 Days
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
Time Frame: 84 Days
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
Time Frame: 84 Days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of Fixed Dose Combination (FDC) Compared to Placebo on Non-HDL-C
Time Frame: 84 Days
LS mean percent change in non-high-density lipoprotein cholesterol (Non-HDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the placebo group.
84 Days
Effect of Fixed Dose Combination (FDC) Compared to Placebo on Apolipoprotein B (ApoB)
Time Frame: 84 Days
LS mean percent change in apolipoprotein B (ApoB) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the placebo group.
84 Days
Effect of Obicetrapib Monotherapy Compared to Placebo on Non-HDL-C
Time Frame: 84 Days
LS mean percent change in non-high-density lipoprotein cholesterol (Non-HDL-C) from baseline to Day 84 in the obicetrapib monotherapy 10 mg group compared to the placebo group.
84 Days
Effect of Obicetrapib Monotherapy Compared to Placebo on Apolipoprotein B (ApoB)
Time Frame: 84 Days
LS mean percent change in apolipoprotein B (ApoB) from baseline to Day 84 in the obicetrapib monotherapy 10 mg group compared to the placebo group.
84 Days
Effect of Fixed-Dose Combination (FDC) Compared to Ezetimibe Monotherapy on Non-HDL-C
Time Frame: 84 Days
LS mean percent change in non-high-density lipoprotein cholesterol (Non-HDL-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.
84 Days
Effect of Fixed-Dose Combination (FDC) Compared to Ezetimibe Monotherapy on Apolipoprotein B (ApoB)
Time Frame: 84 Days
LS mean percent change in apolipoprotein B (ApoB) 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.
84 Days
Effect of Fixed-Dose Combination (FDC) Compared to Obicetrapib Monotherapy on Non-HDL-C
Time Frame: 84 Days
LS mean percent change in non-high-density lipoprotein cholesterol (Non-HDL-C) from baseline to Day 84 in the obicetrapib 10 mg/ezetimibe 10 mg fixed-dose combination (FDC) group compared to the obicetrapib monotherapy 10mg group.
84 Days
Effect of Fixed-Dose Combination (FDC) Compared to Obicetrapib Monotherapy on Apolipoprotein B (ApoB)
Time Frame: 84 Days
LS mean percent change in Apolipoprotein B (ApoB) 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.
84 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NewAmsterdam Pharma

Investigators

  • Study Director: Marc Ditmarsch, MD, NewAmsterdam Pharma

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2024

Primary Completion (Actual)

September 25, 2024

Study Completion (Actual)

October 16, 2024

Study Registration Dates

First Submitted

August 15, 2023

First Submitted That Met QC Criteria

August 15, 2023

First Posted (Actual)

August 22, 2023

Study Record Updates

Last Update Posted (Estimated)

October 8, 2025

Last Update Submitted That Met QC Criteria

September 18, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OBEZ-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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