Clinical trial NCT04770389: Randomized Study of Obicetrapib in Combination With Ezetimibe
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dyslipidemias
High Cholesterol
Hypercholesterolemia
Keywords: obicetrapib
statin
LDL-C
cholesterol
atherosclerosis
Lead sponsor: NewAmsterdam Pharma
Sponsor class: INDUSTRY
First posted: 2021-02-25
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-Controlled, Double-Blind, Randomized
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: 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]
timeFrame: 8 weeks
measure: Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: 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]
timeFrame: 8 weeks
Secondary outcomes:
measure: Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo
timeFrame: 8 weeks
measure: Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo
timeFrame: 8 weeks
measure: LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Placebo
timeFrame: 8 weeks
measure: Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo
timeFrame: 8 weeks
measure: Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo
timeFrame: 8 weeks
measure: LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Placebo
timeFrame: 8 weeks
measure: 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]
timeFrame: 8 weeks
measure: 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]
timeFrame: 8 weeks
measure: 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]
timeFrame: 8 weeks
measure: Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald]
timeFrame: 8 weeks
measure: Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald]
timeFrame: 8 weeks
measure: LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Obicetrapib Monotherapy Compared to Ezetimibe Monotherapy [Friedewald]
timeFrame: 8 weeks
measure: Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [Friedewald]
timeFrame: 8 weeks
measure: Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Day 57: Ezetimibe Monotherapy Compared to Placebo [PUC]
timeFrame: 8 weeks
measure: Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy
timeFrame: 8 weeks
measure: Median Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy
timeFrame: 8 weeks
measure: LS Mean Percent Change in Apolipoprotein-B (ApoB) From Baseline to Day 57: Obicetrapib in Combination With Ezetimibe Compared to Ezetimibe Monotherapy
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Clinical Trials Research
state: California
city: Evanston
country: United States
facility: Evanston Premier Healthcare Research LLC
state: Illinois
city: Houston
country: United States
facility: Juno Research, LLC - Medical Center Office
state: Texas
city: Den Haag
country: Netherlands
facility: Medisch Centrum Thomsonplein
city: Den Haag
country: Netherlands
facility: Huisartsen Praktijk Rambharose
city: Rotterdam
country: Netherlands
facility: Huisartsen Praktijk A.M.N. Zijtregto
city: Rotterdam
country: Netherlands
facility: Huisartsen Praktijk van Soerland
city: Zwijndrecht
country: Netherlands
facility: Huisartsen Praktijk Broekman
city: Zwijndrecht
country: Netherlands
facility: Dokters van Nederhoven
Study officials:
References: