Obicetrapib vs Bempedoic Acid on Maximally Tolerated Lipid‑Lowering Therapy in High‑Risk Dyslipidemia: A Randomized Double‑Blind Study

The primary objective is to evaluate the efficacy of obicetrapib compared with bempedoic acid in reducing LDL‑C at Day 84 in patients with dyslipidemia at high to very high cardiovascular risk.

Secondary objectives are to assess the effect of the study drugs on additional lipid parameters and clinical outcomes at Day 84:

• Change in non‑HDL‑C.
• Change in HDL‑C.
• Change in ApoA1.
• Change in Lp(a).
• Change in ApoB.
• Change in triglycerides.
• Proportion of participants achieving cardiovascular risk‑based LDL‑C goals.
• Assessment of safety and tolerability based on adverse events, events of special interest, and clinical laboratory values.

The trial enrolled 88 adult participants, both male and female, who were at least 18 years of age and represented a broad adult age spectrum. All subjects had a diagnosis of dyslipidemia at high to very high cardiovascular risk and were receiving a stable maximally tolerated lipid‑modifying therapy for a minimum of eight weeks, consistent with a lipid‑lowering diet and lifestyle modifications. Eligibility required a fasting serum LDL‑C concentration between 70 mg/dL and 130 mg/dL, fasting triglycerides below 500 mg/dL, and an estimated glomerular filtration rate ( eGFR ) of ≥30 mL/min/1.73 m². Participants were selected based on documented primary non‑familial hypercholesterolemia or mixed dyslipidemia, adherence to stable therapy, and the ability to provide informed consent. Women of childbearing potential were required to use highly effective contraception or maintain abstinence, while men with fertile partners had comparable contraceptive obligations. The cohort comprised patients who met these clinical and laboratory criteria, reflecting a population with controlled comorbidities and consistent background therapy.

The MEDICI study is a Phase 3, double‑blind, randomized, parallel‑group, controlled trial comparing obicetrapib 10 mg tablet with bempedoic acid 180 mg (Nilemdo) in patients with dyslipidemia at high to very high cardiovascular risk. Participants undergo a screening visit (Visit 1) to confirm eligibility, including eGFR ≥ 30 mL/min/1.73 m², fasting LDL‑C 70–130 mg/dL, fasting triglycerides < 500 mg/dL, and stable maximally tolerated lipid‑lowering therapy for ≥ 8 weeks. After randomization, subjects receive the assigned study drug together with matching placebos for 84 days. Study visits are scheduled at baseline (Day 0), Week 4, and Week 12 (Day 84) for efficacy assessments, safety monitoring, vital signs, and laboratory tests. The end‑of‑study visit at Day 84 includes the final lipid profile, evaluation of adverse events, and determination of goal attainment, with LDL‑C as the primary efficacy endpoint. Participant involvement lasts approximately 12 weeks, with additional follow‑up for post‑treatment safety if required. Early termination may occur if a participant withdraws consent, experiences a serious adverse event, fails to adhere to protocol, or if the investigator deems continuation not in the participant’s best interest.

The investigational product Obicetrapib is supplied as a 10 mg oral tablet and is administered once daily by the oral route throughout the treatment period.

The active comparator, Nilemdo 180 mg film‑coated tablets, contains the lipid‑lowering agent bempedoic acid. Each tablet delivers 180 mg and is taken orally once daily in addition to background therapy.

Matching placebos are provided for both active agents. The Obicetrapib matching placebo and the bempedoic acid matching placebo are indistinguishable from their respective active tablets and are administered with the same frequency and route to maintain blinding.

All participants continue their maximally tolerated lipid‑lowering regimen, which may include statins, ezetimibe, or other standard‑of‑care therapies, as background treatment. Study medication dispensing is recorded at each visit, and adherence is assessed by tablet count and electronic diary entries. Dose adjustments are not permitted, and compliance is monitored to ensure ≥80 % of prescribed doses are taken.

The primary efficacy endpoint is the percentage change from baseline to Day 84 in LDL-C for the obicetrapib group compared with the bempedoic‑acid group.

Secondary efficacy assessments include the non‑HDL‑C percentage change, HDL-C percentage change, and the percentage changes from baseline to Day 84 in ApoA1, Lp(a), ApoB, and triglycerides, as well as the overall proportion of participants achieving cardiovascular‑risk‑based LDL‑C targets (<70 mg/dL for high risk and <55 mg/dL for very high risk).

Lipid parameters will be measured using standard clinical laboratory assays at baseline and at Day 84. Percent changes will be calculated relative to baseline for each participant, and comparative analyses will be performed between the obicetrapib and bempedoic‑acid treatment arms.