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

JRCT ID: jRCT2031220095

Registered date:28/05/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Dyslipidemia
• Date of first enrollment: 28/06/2022
• Target sample size: 100
• Study type: Interventional

Intervention(s)

- 2.5 mg obicetrapib (one 2.5 mg obicetrapib tablet);
- 5 mg obicetrapib (one 5 mg obicetrapib tablet);
- 10 mg obicetrapib (one 10 mg obicetrapib tablet); or
- Placebo (1 placebo tablet)

Outcome(s)

• Primary Outcome: To evaluate the efficacy of obicetrapib, compared to placebo, in reducing serum low-density lipoprotein cholesterol (LDL-C) measured at Day 56 (Visit 5) when taken as an adjunct to a pre-existing stable statin therapy regime.

Secondary Outcome

- To evaluate the effect of obicetrapib, compared to placebo, on serum apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations at Day 56 (Visit 5), when taken as an adjunct to pre-existing stable statin therapy;
- To assess the mean plasma levels of obicetrapib at steady state on Day 56 (Visit 5) and Day 84 (Visit 6); and
- To evaluate the safety and tolerability profile of obicetrapib in Japanese subjects.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

1. Understanding of the study procedures, willingness to adhere to the study schedules, and agreement to participate in the study by giving written informed consent prior to screening procedures;
2. Japanese men or women, 18 to 80 years of age, inclusive, at the Screening Visit;
o 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.
o Women of childbearing potential must have a negative urine pregnancy test at the Screening Visit. Note: Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the Investigator:
- They have had a hysterectomy or tubal ligation at a minimum of 1 cycle prior to signing the ICF; or
- They are postmenopausal, defined as >=1 year since their last menstrual period for women >=55 years of age or >=1 year since their last menstrual period and have a follicle-stimulating hormone (FSH) level in the postmenopausal range for women <55 years of age.
o Women of childbearing potential must agree to complete abstinence or to use an effective method of avoiding pregnancy from screening to 90 days after the last visit. Men whose partners are of childbearing potential must agree to complete abstinence or to have the partner use an effective method of avoiding pregnancy from screening to 90 days after the last visit. Effective methods of avoiding pregnancy are contraceptive methods with a Pearl index of <1 (oral contraceptives or intrauterine devices) used consistently and correctly o a sterile sexual partner;
3. Patients that have not achieved treatment goals in accordance with the 2022 Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases and have documented LDL-C > 70 mg/dL or non-HDL-C >100 mg/dL, and TG < 400 mg/dL, within the last 3 months. If a historical LDL-C or non-HDL-C, and TG values are not available within the last 3 months, a fasting lipid profile to verify eligibility will be required by the central laboratory at the Screening Visit.
4. Currently receiving stable statin therapy with either atorvastatin 10 or 20 mg/day or rosuvastatin 5 or 10 mg/day ONLY for at least 8 weeks prior to screening with the intention of remaining on the same stable dose throughout the study duration.
o Patients on stable statin therapy with either atorvastatin or rosuvastatin AND taking concomitant daily oral ezetimibe as a second line agent are also eligible to participate.

Exclude criteria

1. Body mass index >=35 kg/m2 at the Screening Visit;
2. Current clinically active/acute episode of CV disease, including but not limited to:
o Major adverse CV event within 3 months prior to randomization, including:
- Non-fatal myocardial infarction;
- Non-fatal stroke;
- Hospitalization for heart failure; or
- Hospitalization for unstable angina.
o New York Heart Association Functional Classification Class III or IV heart failure.
3. Have an existing diagnosis of homozygous familial hypercholesterolemia;
4. Have an existing diagnosis of CETP deficiency;
5. Glycosylated hemoglobin (HbA1c) >=10% at the Screening Visit;
6. Uncontrolled hypertension, i.e., supine systolic blood pressure >=160 mmHg and/or supine diastolic blood pressure >=100 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;
7. Active muscle disease or persistent creatine kinase (CK) 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;
8. Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2, calculated using the Chronic Kidney Disease Epidemiology Collaboration equation;
9. Hepatic dysfunction as evidenced by any laboratory abnormality as follows: gamma-glutamyl transferase, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >2 x ULN, or total bilirubin >1.5 x ULN;
10. Anemia, defined as hemoglobin concentration <11 g/dL for men and hemoglobin concentration <9 g/dL for women;
11. History of malignancy within 5 years prior to screening, with the exception of non-melanoma skin cancers;
12. History of alcohol and/or drug abuse within 5 years prior to screening;
13. Treatment with a statin that is not either atorvastatin or rosuvastatin;
14. Treatment with other investigational products or devices within 30 days or 5 half-lives, whichever is longer, prior to screening;
15. Treatment with any PCSK9 inhibitor within 10 weeks prior to randomization or bempedoic acid within 2 weeks prior to randomization;
16. Evidence of any other clinically significant, non-cardiac disease or condition that, in the opinion of the Investigator, would preclude participant in the study; or
17. Known CETP inhibitor allergy or intolerance.

Related Information

• Primary Sponsor: Kanmuri Kazuhiro
• Secondary ID(s): NCT05421078