A Dose-Finding Study in Japanese Patients to Evaluate the Effect of Obicetrapib as an Adjunct to Stable Statin Therapy.

Phase 2

Completed

Conditions: Dyslipidemia
Hypercholesterolemia
High Cholesterol

Interventions: Drug: Placebo
Drug: Obicetrapib

Registration Number: NCT05421078

Lead Sponsor: NewAmsterdam Pharma

Brief Summary: This study will be a placebo-controlled, double-blind, randomized, phase 2 dose-finding study in Japanese patients to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to stable statin therapy.

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 stable statin therapy in Japanese patients. The screening period for this study will take up to 2-weeks. Afterwards, patients will be randomized to placebo, 2.5 mg obicetrapib, 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 visit.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 102

Inclusion Criteria

LDL-C > 70 mg/dL and TG < 400 mg/dL,
Treated with a stable statin therapy; Atorvastatin 20/40 or Simvastatin 10/20

Exclusion Criteria

BMI > or =35 kg/m2
Significant cardiovascular disease
HbA1c > 10%
Uncontrolled hypertension
Active muscle disease
GFR < 60 ml/min
Hepatic dysfunction
Anemia
Existing CETP deficiency
History of Homozygous Familial Hypercholerstrolemia
History of malignancy
Alcohol abuse
Treatment with investigational product
Treatment with PCSK9
Clinically significant condition
Known CETP inhibitor allergy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Once-daily placebo
2.5 mg Obicetrapib	Obicetrapib	once-daily Obicetrapib
5 mg Obicetrapib	Obicetrapib	once-daily Obicetrapib
10 mg Obicetrapib	Obicetrapib	once-daily Obicetrapib

Primary Outcome Measures

Name	Time	Method
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [Friedewald]	8 Weeks	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 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).
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [Friedewald]	8 Weeks	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 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).
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [PUC]	8 Weeks	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).
Median Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [PUC]	8 Weeks	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)
LS Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [PUC]	8 Weeks	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).
Mean Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) [Friedewald]	8 Weeks	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).

Secondary Outcome Measures

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

Trial Locations

Locations (10): Nippon Kokan Fukuyama Hospital
🇯🇵
Fukuyama, Japan
Nakamura Cardiology and Cardiovascular Surgery Clinic
🇯🇵
Itoshima, Japan
Kishiwada Tokushu-Kai Hospital
🇯🇵
Osaka, Japan
Kyosokai AMC NISHI-UMEDA Clinic
🇯🇵
Osaka, Japan
Sakurabashi Watanabe Hospital
🇯🇵
Osaka, Japan
Uji Tokushu-Kai Hospital
🇯🇵
Osaka, Japan
Sanai Hospital
🇯🇵
Saitama, Japan
Shinden Higashi Clinic
🇯🇵
Sendai, Japan
Soka-Sugiura Clinic
🇯🇵
Soka, Japan
Sugiura Clinic
🇯🇵
Tokyo, Japan
Nippon Kokan Fukuyama Hospital
🇯🇵Fukuyama, Japan