A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-0616 in Adults With Hypercholesterolemia
- Conditions
- HypercholesterolemiaMedDRA version: 21.0Level: LLTClassification code 10020604Term: HypercholesterolemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2021-005221-24-DE
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 375
1. Meets 1 of the following ASCVD status/risk categories AND has a fasted LDL-C value in the corresponding LDL-C range at Visit 1 (Screening)
•Has clinical ASCVD
•Has an ASCVD risk equivalent and/or a 10-year risk of having an ASCVD event that is =7.5%
•Has a 10-year risk of having an ASCVD event that is =5.0% and <7.5%
2. Is either on a stable dose of 1 or more lipid-lowering therapies for =30 days before Visit 1 (Screening) or has not received treatment with any lipid-lowering therapy for =30 days before Visit 1 (Screening). Those who are not on a lipid-lowering therapy at Visit 1 (Screening) can either have been previously treated or be treatment naive.
3. Is male or a female, =18 years and =80 years of age, at the time of providing documented informed consent.
4. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Not a WOCBP
OR
• A WOCBP and:
- Uses an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 5 of the study protocol during the intervention period and for at least 8 weeks after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 72 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.7 of the study protocol.
- Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.
5. The participant (or legally acceptable representative) provides documented informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the study without participating in FBR.
6. Is willing and considered able by the investigator to comply with study procedures, including adherence with study intervention, fasting guidelines (Section 5.3.1 of the study protocol), and visit schedule.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75
1. Has a history of homozygous FH based on genetic or clinical criteria [Cuchel, M., et al 2014].
2. Has a history of nephrotic syndrome.
3. Has any clinically significant malabsorption condition.
4. Had unstable angina, a myocardial infarction, percutaneous transluminal coronary angioplasty, transient ischemic attack, or stroke within 3 months before Visit 1 (Screening).
5. Has a planned coronary revascularization procedure within the next 3 months after Visit 1 (Screening).
6. Has poorly controlled diabetes mellitus, defined as A1C =9.0%, at Visit 1 (Screening).
7. Has a known allergy or intolerance to any ofthe ingredients in the study intervention.
8. Has a history of malignancy =3 years before Visit 1 (Screening), except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, which have no timeframe limitations relative to Visit 1 (Screening).
9. Has a severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or administration of study intervention or may interfere with the interpretation of study results and, in the opinion of the investigator, would make the participant inappropriate for entry into this study.
10. Is undergoing or previously underwent an LDL-C apheresis program within 3 months before Visit 1 (Screening).
11. Is receiving treatment with oral semaglutide at Visit 1 (Screening).
12. Meets 1 or more of the following criteria:
• Is on treatment with a PCSK9 inhibitor (siRNA or mAb), an ANGPTL3 inhibitor, or an MTP inhibitor (eg, lomitapide) at Visit 1 (Screening).
• Was previously treated with an siRNA PCSK9 inhibitor within 1 year before Visit 1 (Screening).
• Was previously treated with a mAb PCSK9 inhibitor within 6 months before Visit 1 (Screening).
• Was previously treated with an ANGPTL3 inhibitorwithin 6 months before Visit 1 (Screening).
• Was previously treated with an MTP inhibitor (eg, lomitapide) within 1 month before Visit 1 (Screening).
13. Is currently participating in or has previously participated in an interventional clinical study within 3 months (or 5 half-lives for agents in the previous study, whichever is longer) before Visit 1 (Screening).
14. Has moderate or greater renal insufficiency defined as eGFR <45 mL/min/1.73 m2 at Visit 1 (Screening); eGFR will be calculated according to Appendix 2 of the study protocol.
15. Has laboratory or clinical evidence of clinically significant hepatic conditions, including 1 or more of the following:
• ALT or AST >2X ULN at Visit 1 (Screening).
• A history of hepatitis or liver disease that, in the opinion of the investigator, has been active within the 6 months before Visit 1 (Screening) and may increase the risk associated with study participation or administration of study intervention.
16. Has elevated CK >3X ULN at Visit 1 (Screening).
17. Has a fasting triglyceride value =400 mg/dL (=4.52 mmol/L) at Visit 1 (Screening).
18. Has an abnormal TSH value at Visit 1 (Screening) without a history of hypothyroidism.
Participants with a history of hypothyroidism are eligible if their treatment for this condition is stable for =3 months before Visit 1 (Screening) and their FT4 value at Visit 1 (Screening) is normal.
19. Routinely consumes >3 alcoholic drinks per day. One standard drink is defined as any beverage containing 14 g of pure alcohol (ie, 12 oz of beer, 8 to 9 oz of malt liquor, 5 oz of wine, 1.5 oz of distilled spirits).
20. Has
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To compare the effect of MK-0616 with the effect of placebo on percent change from baseline in LDL-C at Week 8.<br>2. To evaluate the safety and tolerability of each dose of MK-0616. <br>;Secondary Objective: 1. To compare the effect of MK-0616 with the effect of placebo on percent change from baseline in ApoB and non-HDL-C at Week 8.<br>2. To compare the effect of MK-0616 with the effect of placebo on the proportion of participants with LDL-C value at goal at Week 8.;Primary end point(s): 1. Percent Change from Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 8<br>2. Proportion of Participants Who Experience One or More Adverse Events (AEs)<br>3.Proportion of Participants Who Discontinue Study Intervention Due to AEs;Timepoint(s) of evaluation of this end point: 1. Baseline and Week 8<br>2. Up to approximately 16 Weeks<br>3. Up to approximately 8 Weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1.Percent Change from Baseline in Apolipoprotein B (ApoB) at Week 8<br>2. Percent Change from Baseline in Non-High-density Lipoprotein Cholesterol (HDL-C) at Week 8<br>3. Proportion of Participants with LDL-C Value at Goal at Week 8<br>;Timepoint(s) of evaluation of this end point: 1. Baseline and Week 8<br>2. Baseline and Week 8<br>3. Up to 8 Weeks