Randomized Study of Obicetrapib in Combination With Ezetimibe (OCEAN)

A Placebo-Controlled, Double-Blind, Randomized Phase 2 Study to Evaluate the Effect of Obicetrapib in Combination With Ezetimibe in Participants With Mild Dyslipidemia

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Hypercholesterolemia; High Cholesterol
• Intervention / Treatment: Other: Placebo; Drug: Obicetrapib 5mg; Drug: Ezetimibe 10mg

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Den Haag, Netherlands, 2565 KN
    • Medisch Centrum Thomsonplein
  • Den Haag, Netherlands, 2572 GM
    • Huisartsen Praktijk Rambharose
  • Rotterdam, Netherlands, 3037 AN
    • Huisartsen Praktijk A.M.N. Zijtregto
  • Rotterdam, Netherlands, 3067 GJ
    • Huisartsen Praktijk van Soerland
  • Zwijndrecht, Netherlands, 3333 GZ
    • Huisartsen Praktijk Broekman
  • Zwijndrecht, Netherlands, 3334 SB
    • Dokters van Nederhoven
• United States
  • California
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Evanston Premier Healthcare Research LLC
  • Texas
    • Houston, Texas, United States, 77054
      • Juno Research, LLC - Medical Center Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; placebo obicetrapib + placebo ezetimibe; once daily	Other: Placebo; tablet
Experimental: Combination therapy; 5 mg obicetrapib + 10 mg ezetimibe; once daily	Drug: Obicetrapib 5mg; tablet; Other Names: CETP inhibitor; Drug: Ezetimibe 10mg; tablet; Other Names: Antihyperlipidemic
Experimental: Obicetrapib monotherapy; 5 mg obicetrapib + placebo ezetimibe; once daily	Drug: Obicetrapib 5mg; tablet; Other Names: CETP inhibitor
Experimental: Ezetimibe monotherapy; placebo obicetrapib + 10 mg ezetimibe; once daily	Drug: Ezetimibe 10mg; tablet; Other Names: Antihyperlipidemic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]	Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]	Median percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]	Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]	Median percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald]	Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald]	Median percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC]	Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC]	Median percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo	Mean percent change in ApoB from baseline to Day 57	8 weeks
Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo	Median percent change in ApoB from baseline to Day 57	8 weeks
LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo	LS Mean percent change in ApoB from baseline to Day 57	8 weeks
Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo	Mean percent change in Apo-B from baseline to Day 57	8 weeks
Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo	Median percent change in Apo-B from baseline to Day 57	8 weeks
LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo	LS Mean percent change in Apo-B from baseline to Day 57	8 weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy [Friedewald]	Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy [Friedewald]	Median percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy [Friedewald]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald]	Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald]	Median percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C calculated using the Friedewald formula	8 weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald]	Mean percent change in LDL-C from baseline to Day 57; LDL-C determined using the Friedewald formula	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald]	Median percent change in LDL-C from baseline to Day 57; LDL-C calculated using the Friedewald formula	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C calculated using the Friedewald formula	8 weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC]	Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC]	Median percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC]	LS Mean percent change in LDL-C from baseline to Day 57; LDL-C measured using preparative ultracentrifugation (PUC)	8 weeks
Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy	Mean percent change in ApoB from baseline to Day 57	8 weeks
Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy	Median percent change in ApoB from baseline to Day 57	8 weeks
LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy	LS Mean Percent change in ApoB from baseline to Day 57	8 weeks

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): May 7, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: atherosclerosis; LDL-C; cholesterol; statin; obicetrapib
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Lipid Regulating Agents; Ezetimibe; Hypolipidemic Agents
• Other Study ID Numbers: TA-8995-303

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