Study to Evaluate the Effect of Obicetrapib in Combination With Ezetimibe as an Adjunct to HIS Therapy (ROSE2)

A Placebo-Controlled, Double-Blind, Randomized, Phase 2 Study to Evaluate the Effect of Obicetrapib 10 mg Daily in Combination With Ezetimibe 10 mg Daily as an Adjunct to High-Intensity Statin Therapy: The ROSE 2 Study

This study will be a placebo-controlled, double-blind, randomized, phase 2 study to evaluate the efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg and as monotherapy, as an adjunct to high-intensity statin therapy.

Study Overview

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

Detailed Description

This study will be a placebo-controlled, double-blind, randomized, phase 2 study to evaluate the efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg and as monotherapy, as an adjunct to high-intensity statin therapy. The screening period for this study will take up to 2-weeks. Afterwards patients will be randomized to placebo, 10 mg obicetrapib monotherapy, or 10 mg obicetrapib + 10 mg ezetimibe combination therapy for a 12-week treatment period. After the treatment period, patients will continue for a 4-week safety follow-up.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • Velocity Clinical Research - Westlake d.b.a National Research Institute
    • Northridge, California, United States, 91325
      • Valley Clinical Trials, Inc.
  • Florida
    • Ocala, Florida, United States, 34471
      • Ocala Cardiovascular Research
    • Pembroke Pines, Florida, United States, 33024
      • A & R Research Group, LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research - Savannah, GA
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Velocity Clinical Research
  • Illinois
    • Addison, Illinois, United States, 60101
      • Biofortis, Inc
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Heart Clinical Research, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Kentucky
    • Owensboro, Kentucky, United States, 42303
      • Research Integrity LLC
  • Michigan
    • Troy, Michigan, United States, 48085
      • Oakland Medical Research Center
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Meridian Clinical Research- Springdale, OH
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, Inc.
    • Munroe Falls, Ohio, United States, 44240
      • Summit Research Group, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• LDL-C > 70 mg/dL and Triglycerides < 400 mg/dL,
• Treated with a high-intensity statin therapy

Exclusion Criteria:

• BMI >= 40 kg/m2
• Significant cardiovascular disease
• HbA1c >= 10%
• Uncontrolled hypertension
• Active muscle disease
• estimated glomerular filtration rate < 60 mL/min
• Hepatic dysfunction
• History of participation in any clinical trial evaluating obicetrapib
• Anemia
• History of malignancy
• Alcohol abuse
• Treatment with investigational product
• Treatment with PCSK9
• Clinically significant condition
• Known CETP inhibitor allergy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; once-daily placebo tablet and placebo capsule	Other: Obicetrapib placebo; tablets; no active ingredient; Other: Ezetimibe placebo; capsules; no active ingredient
Experimental: monotherapy; once-daily obicetrapib 10 mg tablet and placebo capsule	Drug: Obicetrapib; tablets; Other Names: CETP inhibitor; Other: Ezetimibe placebo; capsules; no active ingredient
Experimental: combination therapy; once-daily obicetrapib 10 mg tablet and ezetimibe 10 mg capsule	Drug: Obicetrapib; tablets; Other Names: CETP inhibitor; Drug: Ezetimibe 10mg; capsules; 10 mg ezetimibe tablets filled into capsule shells, 1 tablet per capsule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald]	Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).	12-weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald]	Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).	12-Weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [Friedewald]	LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).	12-Weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC]	Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	12-Weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC]	Median percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	12-Weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Combination Treatment Group Compared With the Placebo Group [PUC]	LS Mean percent change from Day 1 to Day 84 in Low-Density Lipoprotein Cholesterol (LDL-C) for the obicetrapib 10 mg + ezetimibe 10 mg combination treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	12-Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald]	Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).	12-weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald]	Median percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).	12-Weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [Friedewald]	LS Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C was calculated using the Friedewald equation unless TG ≥400 mg/dL or LDL-C ≤50 mg/dL; if TG ≥400 mg/dL or LDL-C ≤50 mg/dL, then LDL-C level was measured directly by preparative ultracentrifugation (PUC).	12-Weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC]	Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	12-Weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC]	Median percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	12-Weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) for Obicetrapib 10 mg Monotherapy Compared With Placebo [PUC]	LS Mean percent change in Low-Density Lipoprotein Cholesterol (LDL-C) from day 1 to day 84 for obicetrapib 10 mg monotherapy treatment group compared with the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	12-Weeks
Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo	Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group	12-weeks
Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo	Median percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group	12-Weeks
LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib in Combination With Ezetimibe Compared to Placebo	LS Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg plus ezetimibe 10 mg combination treatment group compared with the placebo group	12-Weeks
Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo	Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group	12-weeks
Median Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo	Median percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group	12-Weeks
LS Mean Percent Change in Apolipoprotein-B (ApoB) for Obicetrapib 10 mg Monotherapy Compared With Placebo	LS Mean percent change from day 1 to day 84 in Apolipoprotein-B (ApoB) for the obicetrapib 10 mg monotherapy treatment group compared with the placebo group	12-Weeks

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma
• Investigators: Study Director: Marc Ditmarsch, NewAmsterdam Pharma

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2022
• Primary Completion (Actual): August 12, 2022
• Study Completion (Actual): September 8, 2022

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: October 1, 2022

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; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: TA-8995-202

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