A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
- Conditions
- HypercholesterolemiaFamilial Hypercholesterolemia
- Interventions
- Drug: Enclitide ChlorideDrug: Placebo
- Registration Number
- NCT05261126
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the efficacy and safety of enclitide chloride, an oral PCSK9 inhibitor, in lowering low-density lipoprotein cholesterol (LDL-C) in participants with hypercholesterolemia. The primary hypothesis is that at least one of the four doses of enclitide chloride tested in this study is superior to placebo on percent change from baseline in LDL-C at Week 8.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 381
- History of clinical atherosclerotic cardiovascular disease (ASCVD), or has an ASCVD risk equivalent and/or a 10-year risk of having an ASCVD event ≥5.0%, AND has a corresponding LDL-C that falls within the protocol-specified range at screening.
- Treatment with a stable dose of one or more lipid-lowering therapies for ≥30 days before screening, or has not received treatment with any lipid-lowering therapy for ≥30 days before screening.
- A female participant is not pregnant or breastfeeding, not a woman of child-bearing potential (WOCBP) or is a WOCBP and agrees to follow contraceptive guidance during the intervention period and for at least 8 weeks after the last dose of study intervention.
- History of homozygous familial hypercholesterolemia (FH) based on genetic or clinical criteria.
- History of nephrotic syndrome.
- History of unstable angina, a myocardial infarction, percutaneous transluminal coronary angioplasty, transient ischemic attack, or stroke within 3 months before Screening.
- Has poorly controlled diabetes mellitus, defined as hemoglobin A1C (A1C) ≥9.0% at Screening.
- History of malignancy ≤3 years before screening, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, which have no timeframe limitations relative to screening.
- Currently participating in or has previously participated in an interventional clinical study within 3 months before Screening.
- Has moderate or greater renal insufficiency.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enclitide Chloride 6 mg Enclitide Chloride Participants will receive 6 mg of enlicitide chloride orally QD for 8 weeks Enclitide Chloride 12 mg Enclitide Chloride Participants will receive 12 mg of enlicitide chloride orally QD for 8 weeks Enclitide Chloride 18 mg Enclitide Chloride Participants will receive 18 mg of enlicitide chloride orally QD for 8 weeks Enclitide Chloride 30 mg Enclitide Chloride Participants will receive 30 mg of enlicitide chloride orally QD for 8 weeks Placebo Placebo Participants will receive enlicitide chloride-matching placebo orally QD for 8 weeks
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experienced One or More Adverse Events (AEs) Up to approximately 17 Weeks An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced at least one AE was reported.
Percentage of Participants Who Discontinued Study Intervention Due to AEs Up to approximately 9 Weeks An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to AEs was reported.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 8 Baseline and up to Week 8 Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in LDL-C. Based on a constrained longitudinal analysis (cLDA) model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in LDL-C at week 8 was reported.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Apolipoprotein B (ApoB) at Week 8 Baseline and up to Week 8 Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in ApoB. The least square mean and 95% CI were obtained from fitting a cLDA model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in ApoB at week 8 was reported.
Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at Week 8 Baseline and up to Week 8 Blood samples were collected at baseline and after 8 weeks of treatment to assess mean percent change in non-HDL-C. The least square mean and 95% CI were obtained from fitting a cLDA model including terms for treatment, time, baseline statin intensity, baseline renal function, and the interaction of treatment by time. The percent change from baseline in non-HDL-C at week 8 was reported.
Percentage of Participants With LDL-C Value at Goal at Week 8 Week 8 LDL-C goal was defined as: LDL-C \<70 mg/dL (\<1.81 mmol/L) in participants with clinical atherosclerotic cardiovascular disease (ASCVD), LDL-C \<100 mg/dL (\<2.59 mmol/L) in participants with an ASCVD risk-equivalent and/or a 10-year risk of having an ASCVD event that is ≥7.5%, OR LDL-C \<130 mg/dL (\<3.37mmol/L) in participants with a 10-year risk of having an ASCVD event that is ≥5.0% and \<7.5%. The percentage of participants with LDL-C value at goal at week 8 were reported.
Trial Locations
- Locations (63)
Dallas Diabetes Research Center ( Site 0012)
🇺🇸Dallas, Texas, United States
Center for Cardiometabolic Disease Prevention/Baylor College of Medicine ( Site 0051)
🇺🇸Houston, Texas, United States
Midwest Institute For Clinical Research ( Site 0036)
🇺🇸Indianapolis, Indiana, United States
Northeast Clinical Research of San Antonio ( Site 0014)
🇺🇸San Antonio, Texas, United States
Nordlandssykehuset ( Site 0709)
🇳🇴Bodø, Nordland, Norway
Centro de Estudios de Investigacion Metabolicos y Cardiovasculares-Subinvestigation ( Site 0201)
🇲🇽Ciudad Madero, Tamaulipas, Mexico
Hospital Angeles Xalapa-Internal Medicine-Cardiology ( Site 0202)
🇲🇽Xalapa, Veracruz, Mexico
Akershus Universitetssykehus-Hjertemedisinsk Avdeling ( Site 0705)
🇳🇴Lørenskog, Akershus, Norway
Sykehuset i Vestfold-Hjerteseksjonen ( Site 0703)
🇳🇴Tønsberg, Vestfold, Norway
Bio Investigación AMARC, S.C. ( Site 0204)
🇲🇽Ciudad de México, Distrito Federal, Mexico
Medical Care and Research SA de CV ( Site 0211)
🇲🇽Merida, Yucatan, Mexico
Centro de Atención e Investigación Clínica ( Site 0214)
🇲🇽Aguascalientes, Mexico
Heishinkai Medical Group ToCROM Clinic ( Site 1601)
🇯🇵Shinjuku-ku, Tokyo, Japan
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0212)
🇲🇽Mexico City, Distrito Federal, Mexico
Oslo Universitetssykehus Aker-Preventiv kardiologi Aker ( Site 0704)
🇳🇴Oslo, Norway
Unidad biomedica avanzada monterrey-Clinical Trials ( Site 0200)
🇲🇽Monterrey, Nuevo Leon, Mexico
William Harvey Heart Centre ( Site 1308)
🇬🇧London, London, City Of, United Kingdom
Ege University Medicine of Faculty-Cardilogy Department ( Site 1003)
🇹🇷Bornova, Izmir, Turkey
Oslo Universitetssykehus Rikshospitalet-Kardiologisk avdeling ( Site 0702)
🇳🇴Oslo, Norway
Oslo Universitetssykehus Aker-Lipidklinikken ( Site 0700)
🇳🇴Oslo, Norway
Royal Free Hospital ( Site 1311)
🇬🇧London, England, United Kingdom
Oslo Universitetssykehus Ullevål-Hjertemedisinsk avdeling, Ullevål ( Site 0701)
🇳🇴Oslo, Norway
Hacettepe Universitesi ( Site 1002)
🇹🇷Ankara, Turkey
Clinical Trials Research ( Site 0007)
🇺🇸Sacramento, California, United States
Westside Medical Associates of Los Angeles ( Site 0026)
🇺🇸Beverly Hills, California, United States
National Research Institute (NRI) - Santa Ana ( Site 0024)
🇺🇸Santa Ana, California, United States
Alliance for Multispecialty Research, LLC ( Site 0050)
🇺🇸Coral Gables, Florida, United States
Healthcare Research Network - Chicago ( Site 0037)
🇺🇸Flossmoor, Illinois, United States
Excel Medical Clinical Trials ( Site 0042)
🇺🇸Boca Raton, Florida, United States
ForCare Clinical Research ( Site 0017)
🇺🇸Tampa, Florida, United States
Cotton O'Neil Mulvane ( Site 0022)
🇺🇸Topeka, Kansas, United States
Jubilee Clinical Research ( Site 0047)
🇺🇸Las Vegas, Nevada, United States
New Mexico Clinical Research & Osteoporosis Center ( Site 0032)
🇺🇸Albuquerque, New Mexico, United States
The University of Mississippi Medical Center-Clinical Research and Trials Unit ( Site 0028)
🇺🇸Jackson, Mississippi, United States
Mid Hudson Medical Research ( Site 0004)
🇺🇸New Windsor, New York, United States
altoona center for clinical research ( Site 0045)
🇺🇸Duncansville, Pennsylvania, United States
Piedmont Research Partners ( Site 0005)
🇺🇸Fort Mill, South Carolina, United States
National Clinical Research, Inc-research office ( Site 0019)
🇺🇸Richmond, Virginia, United States
Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0504)
🇩🇪München, Bayern, Germany
Kardiologische Gemeinschaftspraxis ( Site 0502)
🇩🇪Nuremberg, Bayern, Germany
Charité Campus Virchow-Klinikum ( Site 0505)
🇩🇪Berlin, Germany
Ambulantes Herzzentrum Kassel ( Site 0501)
🇩🇪Kassel, Hessen, Germany
Universitätsklinikum Leipzig ( Site 0500)
🇩🇪Leipzig, Sachsen, Germany
Chubu Rosal Hospital ( Site 1612)
🇯🇵Nagoya, Aichi, Japan
Kyoto Okamoto Memorial Hospital ( Site 1611)
🇯🇵Kuse-gun Kumiyama-cho, Kyoto, Japan
Medical Corporation Heishinkai OCROM Clinic ( Site 1600)
🇯🇵Suita-shi, Osaka, Japan
Seiwa Clinic ( Site 1605)
🇯🇵Adachi-ku, Tokyo, Japan
Kitada Clinic ( Site 1604)
🇯🇵Osaka-city, Osaka, Japan
meiwa hospital ( Site 1602)
🇯🇵Chiyoda-ku, Tokyo, Japan
Keimyung University Dongsan Hospital ( Site 1703)
🇰🇷Daegu, Taegu-Kwangyokshi, Korea, Republic of
Sekino Hospital ( Site 1603)
🇯🇵Toshimaku, Tokyo, Japan
Severance Hospital, Yonsei University Health System ( Site 1701)
🇰🇷Seoul, Korea, Republic of
Hospital Angeles Mocel ( Site 0209)
🇲🇽Mexico City, Distrito Federal, Mexico
Samsung Medical Center ( Site 1700)
🇰🇷Seoul, Korea, Republic of
Instituto Jalisciense de Investigacion en Diabetes y Obesidad-Endocrinology ( Site 0205)
🇲🇽Guadalajara, Jalisco, Mexico
Stavanger Universitetssykehus ( Site 0706)
🇳🇴Stavanger, Rogaland, Norway
Eskisehir Osmangazi University-Cardiology ( Site 1000)
🇹🇷Eskisehir, Turkey
Queen Elizabeth University Hospital-Glasgow Clinical Research Facility ( Site 1310)
🇬🇧Glasgow, Glasgow City, United Kingdom
Walsall Manor Hospital ( Site 1309)
🇬🇧West Midlands, Walsall, United Kingdom
Layton Medical Centre ( Site 1303)
🇬🇧Blackpool, Lancashire, United Kingdom
Seoul National University Hospital ( Site 1702)
🇰🇷Seoul, Korea, Republic of
L-MARC Research Center ( Site 0003)
🇺🇸Louisville, Kentucky, United States
Unidad de Investigaci�n Cl�nica Cardiometabolica de Occident-Unidad de Investigación Clínica Cardio
🇲🇽Guadalajara, Jalisco, Mexico