A Study of the Efficacy and Safety of MK-0616 (Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)

Hypercholesterolemia Clinical Trial

Official title:

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-0616 in Adults With Hypercholesterolemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05261126
• Other study ID #: 0616-008
• Secondary ID: MK-0616-008jRCT2
• Status: Completed
• Phase: Phase 2
• Start date: March 10, 2022
• Est. completion date: November 28, 2022

Study information

• Verified date: November 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of MK-0616, 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 MK-0616 tested in this study is superior to placebo on percent change from baseline in LDL-C at Week 8.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 381
• Est. completion date: November 28, 2022
• Est. primary completion date: November 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• MK-0616
MK-0616 administered orally
• Placebo
Placebo matching MK-0616 administered orally

Locations

Country	Name	City	State
Germany	Charité Campus Virchow-Klinikum ( Site 0505)	Berlin
Germany	Ambulantes Herzzentrum Kassel ( Site 0501)	Kassel	Hessen
Germany	Universitätsklinikum Leipzig ( Site 0500)	Leipzig	Sachsen
Germany	Klinikum der Ludwig-Maximilians-Universitaet Muenchen ( Site 0504)	München	Bayern
Germany	Kardiologische Gemeinschaftspraxis ( Site 0502)	Nuremberg	Bayern
Japan	Seiwa Clinic ( Site 1605)	Adachi-ku	Tokyo
Japan	meiwa hospital ( Site 1602)	Chiyoda-ku	Tokyo
Japan	Kyoto Okamoto Memorial Hospital ( Site 1611)	Kuse-gun Kumiyama-cho	Kyoto
Japan	Chubu Rosal Hospital ( Site 1612)	Nagoya	Aichi
Japan	Kitada Clinic ( Site 1604)	Osaka-city	Osaka
Japan	Heishinkai Medical Group ToCROM Clinic ( Site 1601)	Shinjuku-ku	Tokyo
Japan	Medical Corporation Heishinkai OCROM Clinic ( Site 1600)	Suita-shi	Osaka
Japan	Sekino Hospital ( Site 1603)	Toshimaku	Tokyo
Korea, Republic of	Keimyung University Dongsan Hospital ( Site 1703)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Samsung Medical Center ( Site 1700)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1702)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System ( Site 1701)	Seoul
Mexico	Centro de Atención e Investigación Clínica ( Site 0214)	Aguascalientes
Mexico	Bio Investigación AMARC, S.C. ( Site 0204)	Ciudad de México	Distrito Federal
Mexico	Centro de Estudios de Investigacion Metabolicos y Cardiovasculares-Subinvestigation ( Site 0201)	Ciudad Madero	Tamaulipas
Mexico	Instituto Jalisciense de Investigacion en Diabetes y Obesidad-Endocrinology ( Site 0205)	Guadalajara	Jalisco
Mexico	Unidad de Investigaci?n Cl?nica Cardiometabolica de Occident-Unidad de Investigación Clínica Cardio	Guadalajara	Jalisco
Mexico	Medical Care and Research SA de CV ( Site 0211)	Merida	Yucatan
Mexico	Hospital Angeles Mocel ( Site 0209)	Mexico City	Distrito Federal
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0212)	Mexico City	Distrito Federal
Mexico	Unidad biomedica avanzada monterrey-Clinical Trials ( Site 0200)	Monterrey	Nuevo Leon
Mexico	Hospital Angeles Xalapa-Internal Medicine-Cardiology ( Site 0202)	Xalapa	Veracruz
Norway	Nordlandssykehuset ( Site 0709)	Bodø	Nordland
Norway	Akershus Universitetssykehus-Hjertemedisinsk Avdeling ( Site 0705)	Lørenskog	Akershus
Norway	Oslo Universitetssykehus Aker-Lipidklinikken ( Site 0700)	Oslo
Norway	Oslo Universitetssykehus Aker-Preventiv kardiologi Aker ( Site 0704)	Oslo
Norway	Oslo Universitetssykehus Rikshospitalet-Kardiologisk avdeling ( Site 0702)	Oslo
Norway	Oslo Universitetssykehus Ullevål-Hjertemedisinsk avdeling, Ullevål ( Site 0701)	Oslo
Norway	Stavanger Universitetssykehus ( Site 0706)	Stavanger	Rogaland
Norway	Sykehuset i Vestfold-Hjerteseksjonen ( Site 0703)	Tønsberg	Vestfold
Turkey	Hacettepe Universitesi ( Site 1002)	Ankara
Turkey	Ege University Medicine of Faculty-Cardilogy Department ( Site 1003)	Bornova	Izmir
Turkey	Eskisehir Osmangazi University-Cardiology ( Site 1000)	Eskisehir
United Kingdom	Layton Medical Centre ( Site 1303)	Blackpool	Lancashire
United Kingdom	Queen Elizabeth University Hospital-Glasgow Clinical Research Facility ( Site 1310)	Glasgow	Glasgow City
United Kingdom	Royal Free Hospital ( Site 1311)	London	England
United Kingdom	William Harvey Heart Centre ( Site 1308)	London	London, City Of
United Kingdom	Walsall Manor Hospital ( Site 1309)	West Midlands	Walsall
United States	New Mexico Clinical Research & Osteoporosis Center ( Site 0032)	Albuquerque	New Mexico
United States	Westside Medical Associates of Los Angeles ( Site 0026)	Beverly Hills	California
United States	Excel Medical Clinical Trials ( Site 0042)	Boca Raton	Florida
United States	Alliance for Multispecialty Research, LLC ( Site 0050)	Coral Gables	Florida
United States	Dallas Diabetes Research Center ( Site 0012)	Dallas	Texas
United States	altoona center for clinical research ( Site 0045)	Duncansville	Pennsylvania
United States	Healthcare Research Network - Chicago ( Site 0037)	Flossmoor	Illinois
United States	Piedmont Research Partners ( Site 0005)	Fort Mill	South Carolina
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	The University of Mississippi Medical Center-Clinical Research and Trials Unit ( Site 0028)	Jackson	Mississippi
United States	Jubilee Clinical Research ( Site 0047)	Las Vegas	Nevada
United States	L-MARC Research Center ( Site 0003)	Louisville	Kentucky
United States	Mid Hudson Medical Research ( Site 0004)	New Windsor	New York
United States	National Clinical Research, Inc-research office ( Site 0019)	Richmond	Virginia
United States	Clinical Trials Research ( Site 0007)	Sacramento	California
United States	Northeast Clinical Research of San Antonio ( Site 0014)	San Antonio	Texas
United States	National Research Institute (NRI) - Santa Ana ( Site 0024)	Santa Ana	California
United States	ForCare Clinical Research ( Site 0017)	Tampa	Florida
United States	Cotton O'Neil Mulvane ( Site 0022)	Topeka	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Germany,  Japan,  Korea, Republic of,  Mexico,  Norway,  Turkey,  United Kingdom, 

References & Publications (1)

Ballantyne CM, Banka P, Mendez G, Garcia R, Rosenstock J, Rodgers A, Mendizabal G, Mitchel Y, Catapano AL. Phase 2b Randomized Trial of the Oral PCSK9 Inhibitor MK-0616. J Am Coll Cardiol. 2023 Apr 25;81(16):1553-1564. doi: 10.1016/j.jacc.2023.02.018. Epu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at 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.	Baseline and up to Week 8
Primary	Percentage of Participants Who Experienced One or More Adverse Events (AEs)	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.	Up to approximately 17 Weeks
Primary	Percentage of Participants Who Discontinued Study Intervention Due to AEs	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.	Up to approximately 9 Weeks
Secondary	Percent Change From Baseline in Apolipoprotein B (ApoB) at 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.	Baseline and up to Week 8
Secondary	Percent Change From Baseline in Non-High-density Lipoprotein Cholesterol (Non-HDL-C) at 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.	Baseline and up to Week 8
Secondary	Percentage of Participants With LDL-C Value at Goal at 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.	Week 8

External Links

•   Merck Clinical Trials Information