Randomized Study of Obicetrapib in Combination With Ezetimibe (OCEAN)

NewAmsterdam Pharma

Status and phase: Completed; Phase 2

Conditions: Dyslipidemias; Hypercholesterolemia; High Cholesterol

Treatments: Drug: Obicetrapib 5mg; Other: Placebo; Drug: Ezetimibe 10mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04770389

TA-8995-303

Details and patient eligibility

About

This study will be a placebo-controlled, double-blind, randomized, phase 2 study in participants with mild dyslipidemia to evaluate the efficacy, safety, and tolerability of obicetrapib and ezetimibe combination therapy.

Full description

This study will be a placebo-controlled, double-blind, randomized, phase 2 study in participants with mild dyslipidemia to evaluate the efficacy, safety, and tolerability of obicetrapib and ezetimibe combination therapy. The screening period for this study will take up to 2 weeks. Following the screening period, eligible patients will be randomized to placebo, 5 mg obicetrapib + 10 mg ezetimibe; 5 mg obicetrapib + placebo ezetimibe; or placebo obicetrapib + 10 mg ezetimibe for an 8 week treatment period. After the treatment period, patients will continue for a 4 week safety follow-up and a 8 week PK follow-up.

Enrollment: 112 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Understanding of the study procedures, willingness to adhere to the study schedules and diet, and agreement to participate in the study by giving written informed consent prior to Screening procedures
• Men or women 18 to 70 years of age, inclusive
• Women 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
• Women of childbearing potential must have a negative urine pregnancy test at the Screening Visit.
• Women of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit. Men whose partners are of childbearing potential must agree to use an effective method of avoiding pregnancy from the Screening Visit to 90 days after the last visit.
• Fasting LDL-C levels >2.5 mmol/L (>100 mg/dL) and <4.5 mmol/L (<175 mg/dL) and TG levels <4.5 mmol/L (<400 mg/dL) (Visit 1) and
• Willingness to maintain a stable diet and physical activity level throughout the study

Exclusion criteria

• Body mass index >= 40 kg/m2
• Participation in another clinical study involving an investigational or marketed drug within 30 days prior to the Screening Visit
• Currently taking any lipid-altering therapy
• Any clinical manifestation of atherosclerotic CVD or any evidence of ischemic coronary disease present on the 12-lead ECG at the Screening Visit
• Diagnosis of type 1 or type 2 diabetes mellitus; or HbA1c >= 6.5% at the Screening visit if no prior diagnosis of diabetes mellitus
• Uncontrolled hypertension ie, sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >90 mmHg taken as the average of triplicate measurements.

One retest will be allowed, at which point if the retest result is no longer exclusionary, the participant may be randomized

• Active muscle disease or persistent creatine kinase concentration >3 x the upper limit of normal (ULN). One retest will be allowed after 1 week to verify the result, at which point if the retest result is no longer exclusionary, the participant may be randomized
• History of torsades de pointes
• Estimated glomerular filtration rate <60 mL/min calculated using the Chronic Kidney Disease Epidemiology Collaboration equation
• Hepatic dysfunction as evidenced by any laboratory abnormality as follows: gamma- glutamyl transferase, alanine aminotransferase, or aspartate aminotransferase >2 x ULN, or total bilirubin >1.5 x ULN
• Anemia, defined as hemoglobin concentration <11 g/dL for males and hemoglobin concentration <9 g/dL for females
• History of malignancy within the past 5 years, with the exception of non-melanoma skin cancers
• Evidence of any other clinically significant non-cardiac disease or condition that, in the opinion of the Investigator, would preclude participation in the study
• Known ezetimibe or CETP inhibitor allergy or intolerance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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112 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

placebo obicetrapib + placebo ezetimibe; once daily

Treatment:

Other: Placebo

Combination therapy

Experimental group

Description:

5 mg obicetrapib + 10 mg ezetimibe; once daily

Treatment:

Drug: Ezetimibe 10mg

Drug: Obicetrapib 5mg

Obicetrapib monotherapy

Experimental group

Description:

5 mg obicetrapib + placebo ezetimibe; once daily

Treatment:

Drug: Obicetrapib 5mg

Ezetimibe monotherapy

Experimental group

Description:

placebo obicetrapib + 10 mg ezetimibe; once daily

Treatment:

Drug: Ezetimibe 10mg