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

NewAmsterdam Pharma

Status and phase: Active, not recruiting; Phase 3

Conditions: Dyslipidemias; Hypercholesterolemia; High Cholesterol; ASCVD; Familial Hypercholesterolemia

Treatments: Other: Combination Therapy placebo; Drug: Monotherapy ezetimibe; Other: Obicetrapib Placebo; Combination Product: Combination Therapy; Drug: Monotherapy obicetrapib; Other: Ezetimibe Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06005597

OBEZ-301

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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400 participants in 4 patient groups, including a placebo group

Combination Therapy

Experimental group

Description:

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

Treatment:

Other: Ezetimibe Placebo

Combination Product: Combination Therapy

Other: Obicetrapib Placebo

Monotherapy obicetrapib

Experimental group

Description:

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

Treatment:

Other: Ezetimibe Placebo

Drug: Monotherapy obicetrapib

Other: Combination Therapy placebo

Monotherapy ezetimibe

Active Comparator group

Description:

once-daily ezetimibe 10 mg capsule, 2 placebo tablets

Treatment:

Other: Obicetrapib Placebo

Drug: Monotherapy ezetimibe

Other: Combination Therapy placebo

Placebo

Placebo Comparator group

Description:

once-daily placebo tablets (2), placebo capsule

Treatment:

Other: Ezetimibe Placebo

Other: Obicetrapib Placebo

Other: Combination Therapy placebo