Randomized Study of Obicetrapib in Combination With Ezetimibe

Phase 2

Completed

• Conditions: Dyslipidemias; High Cholesterol; Hypercholesterolemia
• Interventions: Other: Placebo; Drug: Obicetrapib 5mg; Drug: Ezetimibe 10mg

• Registration Number: NCT04770389
• Lead Sponsor: NewAmsterdam Pharma

Brief 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.

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 Timeline

• Study First Submitted: 2021-02-22
• Study First Submitted QC: 2021-02-22
• Study Start: 2021-02-23
• Study First Posted: 2021-02-25
• Primary Completion: 2021-05-07
• Study Completion: 2021-06-30
• Status Verified: 2024-03
• Results First Submitted: 2024-03-27
• Results First Submitted QC: 2024-03-27
• Last Update Submitted: 2024-03-27
• Results First Posted: 2024-04-24
• Last Update Posted: 2024-04-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	placebo obicetrapib + placebo ezetimibe; once daily
Combination therapy	Obicetrapib 5mg	5 mg obicetrapib + 10 mg ezetimibe; once daily
Combination therapy	Ezetimibe 10mg	5 mg obicetrapib + 10 mg ezetimibe; once daily
Obicetrapib monotherapy	Obicetrapib 5mg	5 mg obicetrapib + placebo ezetimibe; once daily
Ezetimibe monotherapy	Ezetimibe 10mg	placebo obicetrapib + 10 mg ezetimibe; once daily

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (9)

Clinical Trials Research; 🇺🇸 Lincoln, California, United States

Huisartsen Praktijk A.M.N. Zijtregto; 🇳🇱 Rotterdam, Netherlands

Huisartsen Praktijk van Soerland; 🇳🇱 Rotterdam, Netherlands

Medisch Centrum Thomsonplein; 🇳🇱 Den Haag, Netherlands

Huisartsen Praktijk Rambharose; 🇳🇱 Den Haag, Netherlands

Dokters van Nederhoven; 🇳🇱 Zwijndrecht, Netherlands

Huisartsen Praktijk Broekman; 🇳🇱 Zwijndrecht, Netherlands

Evanston Premier Healthcare Research LLC; 🇺🇸 Evanston, Illinois, United States

Juno Research, LLC - Medical Center Office; 🇺🇸 Houston, Texas, United States