Randomized Study of Obicetrapib as an Adjunct to Statin Therapy (ROSE)

A Placebo-Controlled, Double-Blind, Randomized, Phase 2 Dose-Finding Study to Evaluate the Effect of Obicetrapib as an Adjunct to High-Intensity Statin Therapy

This study will be a placebo-controlled, double-blind, randomized, phase 2 dose-finding study to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to high-intensity statin therapy.

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Hypercholesterolemia; High Cholesterol
• Intervention / Treatment: Drug: Obicetrapib

Detailed Description

This study will be a placebo-controlled, double-blind, randomized, phase 2 dose-finding study to evaluate the efficacy, safety, and tolerability of obicetrapib 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, 5 mg obicetrapib or 10 mg obicetrapib for an 8-week treatment period. After the treatment period, patients will continue for a 4-week safety follow-up and a 15-week PK follow-up.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
  • California
    • Huntington Park, California, United States, 90255
      • National Research Institute - Huntington Park
    • Los Angeles, California, United States, 90057
      • National Research Institute - Wilshire
    • Sacramento, California, United States, 95821
      • Clinical Trials Research
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Ocala, Florida, United States, 34474
      • Ocala Cardiovascular Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • IACT Health
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Evanston Premier Healthcare Research LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
  • Michigan
    • Troy, Michigan, United States, 48085
      • Oakland Medical Research Center
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Diabetes and Endocrinology Consultants, P.C.
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Metabolic and Atherosclerosis Research Center
    • Munroe Falls, Ohio, United States, 44262
      • Summit Research Group, LLC
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
    • Rapid City, South Dakota, United States, 57701
      • Monument Health Clinical Research
  • Texas
    • Houston, Texas, United States, 77040
      • Juno Research, LL
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center

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 TG < 400 mg/dL,
• Treated with a high-intensity statin therapy

Exclusion Criteria:

• BMI > 40 kg/m
• Significant cardiovascular disease
• HbA1c > 10%
• Uncontrolled hypertension
• Active muscle disease
• GFR < 60 ml/min
• Hepatic dysfunction
• 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	Drug: Obicetrapib; tablets; Other Names: CETP inhibitor
Experimental: obicetrapib 5 mg; once-daily obicetrapib	Drug: Obicetrapib; tablets; Other Names: CETP inhibitor
Experimental: obicetrapib 10 mg; once-daily obicetrapib	Drug: Obicetrapib; tablets; Other Names: CETP inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [Friedewald]	Mean percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to 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),	8-weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [Friedewald]	Median Percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. [Friedewald] 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),	8-Weeks
LS Mean Percent Change Iin Low-Density Lipoprotein Cholesterol (LDL-C) [Friedewald]	LS mean percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. [Friedewald] 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),	8-Weeks
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [PUC]	Mean Percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	8-Weeks
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [PUC]	Median Percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C level was measured by preparative ultracentrifugation (PUC).	8-Weeks
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [PUC]	LS Mean Percent change from Day 1 to Day 56 in Low-Density Lipoprotein Cholesterol (LDL-C) for each obicetrapib group compared to the placebo group. LDL-C level was measured directly by preparative ultracentrifugation (PUC).	8-Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change in Apolipoprotein B (ApoB)	Mean percent change from baseline to Day 56 in apolipoprotein B (ApoB) (mg/dL) for each obicetrapib group compared with the placebo group.	8-Weeks
Median Percent Change in Apolipoprotein B (ApoB)	Median percent change from baseline to Day 56 in apolipoprotein B (ApoB) (mg/dL) for each obicetrapib group compared with the placebo group.	8-Week
LS Mean Percent Change in Apolipoprotein B (ApoB)	Median percent change from baseline to Day 56 in apolipoprotein B (ApoB) (mg/dL) for each obicetrapib group compared with the placebo group.	8-Weeks
Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Mean percent change from baseline to Day 56 in non-high-density lipoprotein cholesterol (non-HDL-C) (mg/dL) for each obicetrapib group compared with the placebo group	8-weeks
Median Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	Median percent change from baseline to Day 56 in non-high-density lipoprotein cholesterol (non-HDL-C) (mg/dL) for each obicetrapib group compared with the placebo group	8-Weeks
LS Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	LS Mean percent change from baseline to Day 56 in non-high-density lipoprotein cholesterol (non-HDL-C) (mg/dL) for each obicetrapib group compared with the placebo group	8-Weeks
Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C)	Mean percent change from baseline to Day 56 in High-density lipoprotein cholesterol (HDL-C) (mg/dL) for each obicetrapib group compared with the placebo group.	8-weeks
Median Percent Change in High-density Lipoprotein Cholesterol (HDL-C)	Median percent change from baseline to Day 56 in High-density lipoprotein cholesterol (HDL-C) (mg/dL) for each obicetrapib group compared with the placebo group.	8-Weeks
LS Mean Percent Change in High-density Lipoprotein Cholesterol (HDL-C)	LS mean percent change from baseline to Day 56 in High-density lipoprotein cholesterol (HDL-C) (mg/dL) for each obicetrapib group compared with the placebo group.	8-Weeks

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma

Publications and helpful links

General Publications

• Nicholls SJ, Ditmarsch M, Kastelein JJ, Rigby SP, Kling D, Curcio DL, Alp NJ, Davidson MH. Lipid lowering effects of the CETP inhibitor obicetrapib in combination with high-intensity statins: a randomized phase 2 trial. Nat Med. 2022 Aug;28(8):1672-1678. doi: 10.1038/s41591-022-01936-7. Epub 2022 Aug 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Actual): May 24, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: September 1, 2021

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
• Other Study ID Numbers: TA-8995-201

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