Randomized Study of Obicetrapib in Combination With Ezetimibe

Hypercholesterolemia Clinical Trial

— OCEAN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04770389
• Other study ID #: TA-8995-303
• Status: Completed
• Phase: Phase 2
• Start date: February 23, 2021
• Est. completion date: June 30, 2021

Study information

• Verified date: March 2024
• Source: NewAmsterdam Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: June 30, 2021
• Est. primary completion date: May 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Dyslipidemias
• High Cholesterol
• Hypercholesterolemia

Intervention

Drug:
• Obicetrapib 5mg
tablet
• Ezetimibe 10mg
tablet

Other:
• Placebo
tablet

Locations

Country	Name	City	State
Netherlands	Huisartsen Praktijk Rambharose	Den Haag
Netherlands	Medisch Centrum Thomsonplein	Den Haag
Netherlands	Huisartsen Praktijk A.M.N. Zijtregto	Rotterdam
Netherlands	Huisartsen Praktijk van Soerland	Rotterdam
Netherlands	Dokters van Nederhoven	Zwijndrecht
Netherlands	Huisartsen Praktijk Broekman	Zwijndrecht
United States	Evanston Premier Healthcare Research LLC	Evanston	Illinois
United States	Juno Research, LLC - Medical Center Office	Houston	Texas
United States	Clinical Trials Research	Lincoln	California

Sponsors (1)

Lead Sponsor	Collaborator
NewAmsterdam Pharma

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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