Clinical trial NCT06005597: Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dyslipidemias
Hypercholesterolemia
Familial Hypercholesterolemia
ASCVD
High Cholesterol
Keywords: obicetrapib
statin
LDL-C
cholesterol
atherosclerosis
Lead sponsor: NewAmsterdam Pharma
Sponsor class: INDUSTRY
First posted: 2023-08-22
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled, double blind, randomized
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of combination therapy compared to placebo on LDL-C
timeFrame: 84-Days
measure: Effect of combination therapy compared to ezetimibe 10 mg monotherapy on LDL-C
timeFrame: 84-Days
measure: Effect of combination therapy compared to obicetrapib 10 mg monotherapy on LDL-C
timeFrame: 84-Days
measure: Effect of obicetrapib 10 mg monotherapy compared to placebo on LDL-C
timeFrame: 84-Days
Secondary outcomes:
measure: Effect of combination therapy compared to placebo on non-HDL-C
timeFrame: 84-Days
measure: Effect of combination therapy compared to placebo on Apolipoprotein B (ApoB)
timeFrame: 84-Days
measure: Effect of obicetrapib 10 mg monotherapy compared to placebo on non-HDL-C
timeFrame: 84-Days
measure: Effect of obicetrapib 10 mg monotherapy compared to placebo on ApoB
timeFrame: 84-Days
measure: Effect of combination therapy compared compared to ezetimibe 10 mg monotherapy on non-HDL-C
timeFrame: 84-Days
measure: Effect of combination therapy compared to ezetimibe 10 mg monotherapy on ApoB
timeFrame: 84-Days
measure: Effect of combination therapy compared to obicetrapib 10 mg monotherapy on non-HDL-C
timeFrame: 84-Days
measure: Effect of combination therapy compared to obicetrapib 10 mg monotherapy on ApoB
timeFrame: 84-Days
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: East Valley Diabetes & Endocrinology
state: Arizona
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Columbus
country: United States
facility: Centricity Research - Columbus
state: Georgia
city: Gainesville
country: United States
facility: Center for Advanced Research and Education
state: Georgia
city: Johns Creek
country: United States
facility: NSC Research
state: Georgia
city: Woodstock
country: United States
facility: North Georgia Clinical Research
state: Georgia
city: Skokie
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
city: Munster
country: United States
facility: Cardiovascular Research of Northwest Indiana, LLC
state: Indiana
city: Bossier City
country: United States
facility: Grace Research, LLC - Bossier City, LA
state: Louisiana
city: Eunice
country: United States
facility: Horizon Research Group of Opelousas
state: Louisiana
city: Baltimore
country: United States
facility: Maryland Cardiovascular Specialists
state: Maryland
city: Salisbury
country: United States
facility: TidalHealth Peninsula Regional, Inc.
state: Maryland
city: Bay City
country: United States
facility: McClaren Bay Heart and Vascular
state: Michigan
city: Buckley
country: United States
facility: Northern Pines Health Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Troy
country: United States
facility: Oakland Medical Research Center
state: Michigan
city: Saint Cloud
country: United States
facility: CentraCare Heart & Vascular Center
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis Heart and Vascular Cardiology
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Asheboro
country: United States
facility: Triad Internal Medicine
state: North Carolina
city: Cary
country: United States
facility: Cary Research Group, LLC
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Clinical Research, LLC
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Heart and Vascular Institute
state: North Carolina
city: Morehead City
country: United States
facility: Lucas Research, Inc
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health Associates
state: North Carolina
city: Cincinnati
country: United States
facility: Metabolic and Atherosclerosis Research Center
state: Ohio
city: Stow
country: United States
facility: Summit Research Group, LLC
state: Ohio
city: Camp Hill
country: United States
facility: Capital Area Research
state: Pennsylvania
city: Rapid City
country: United States
facility: Monument Health Clinical Research, a department of Monument Health Rapid City Hospital, Inc
state: South Dakota
city: Chattanooga
country: United States
facility: Chattanooga Research & Medicine, PLLC
state: Tennessee
city: Powell
country: United States
facility: Cardiovascular Research of Knoxville
state: Tennessee
city: Amarillo
country: United States
facility: PharmaTex Research, LLC
state: Texas
city: Amarillo
country: United States
facility: Amarillo Heart Clinical Research Institute, Inc
state: Texas
city: Corpus Christi
country: United States
facility: South Texas Clinical Research
state: Texas
city: Fort Worth
country: United States
facility: Diabetes and Thyroid Center of Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC - Medical Center Office
state: Texas
city: Houston
country: United States
facility: DM Clinical Research
state: Texas
city: McKinney
country: United States
facility: Wellness Clinical Research Associates
state: Texas
city: Tomball
country: United States
facility: Northwest Houston Heart Center
state: Texas
city: Clinton
country: United States
facility: Alpine Research Organization, Inc.
state: Utah
city: Danville
country: United States
facility: Spectrum Medical, Inc.
state: Virginia
city: Suffolk
country: United States
facility: Hampton Roads Center for Clinical Research
state: Virginia
Study officials:
affiliation: NewAmsterdam Pharma
name: Marc Ditmarsch, MD
role: STUDY_DIRECTOR
References: