What Is Obicetrapib?
Obicetrapib is an investigational drug currently being studied for its potential to manage various lipid disorders. It is being developed by NewAmsterdam Pharma, which has sponsored all 18 clinical trials involving this medication. The exact mechanism of action for obicetrapib is not detailed in the provided trial descriptions, but it is being investigated as an active treatment for conditions related to high cholesterol and other lipid abnormalities.
Clinical trials for obicetrapib began on February 15, 2021, with the latest trial projected to conclude on October 22, 2025. Across all studies, a total of 14,305 participants have been enrolled. Obicetrapib has been studied as a standalone therapy and in various fixed-dose combinations with other medications, aiming to improve lipid profiles and potentially reduce cardiovascular risk.
Uses and Conditions Under Study
Obicetrapib is primarily under investigation for its role in managing lipid-related disorders, which affect how the body processes fats and cholesterol. These conditions include:
- High Cholesterol, Hypercholesterolemia, Dyslipidemias, Hyperlipoproteinemias, Lipidemia, and Lipid Metabolism: These terms describe various forms of elevated cholesterol or other fats in the blood. Obicetrapib is being studied in seven trials for high cholesterol and hypercholesterolemia, seven trials for dyslipidemias, two trials for lipidemia, and one trial each for hyperlipoproteinemias and lipid metabolism. The drug aims to help lower unhealthy lipid levels to improve overall cardiovascular health.
- Familial Hypercholesterolemia: This is a genetic condition causing very high levels of LDL ("bad") cholesterol from birth, significantly increasing the risk of early heart disease. Obicetrapib is being evaluated in three trials for its potential to manage cholesterol levels in individuals with this inherited disorder.
- Atherosclerotic Cardiovascular Disease (ASCVD): This condition involves the hardening and narrowing of arteries due due to plaque buildup, often linked to high cholesterol. Obicetrapib is being studied in two trials for its potential to impact ASCVD, likely by improving lipid profiles to reduce disease progression.
Additionally, obicetrapib has been studied in healthy volunteers in three trials to assess its safety, tolerability, and how it is processed by the body. One trial also investigated the drug in subjects with hepatic impairment to understand how liver function might affect its pharmacokinetics.
Dosing
Obicetrapib has been studied in various dosage forms and strengths, primarily as oral tablets. The investigational strengths include 2.5 mg, 5 mg, and 10 mg of obicetrapib.
The medication has been evaluated both as a monotherapy and in combination with other drugs commonly used to manage cholesterol and related conditions. These combinations include:
- Obicetrapib/Ezetimibe (a fixed-dose combination tablet, such as 10mg obicetrapib and 10mg ezetimibe)
- Obicetrapib/Evolocumab (for example, 10 mg obicetrapib followed by a combination of 10 mg obicetrapib and 140 mg evolocumab every two weeks)
- Obicetrapib + Atorvastatin
- Obicetrapib + Rosuvastatin
- Obicetrapib + Drospirenone/Ethinyl Estradiol (COC)
Specific dosing regimens have varied across trials, with some studies involving administration for durations such as 8 weeks. The precise frequency of administration (e.g., daily) for all forms is not detailed in the provided trial descriptions, but the tablet form suggests oral intake. All studies have focused on adult populations; no specific pediatric dosing information is available from the provided data.
Side Effects
In clinical trials, the most common side effect reported by patients taking Obicetrapib was influenza, affecting 6.9% of patients compared to 4.8% of those on placebo. Hypertension was also observed in 4.7% of patients receiving Obicetrapib, versus 3.9% on placebo. Other side effects reported by patients taking Obicetrapib included:
- Diarrhea: 2.9% of patients on Obicetrapib experienced diarrhea, compared to 2.8% on placebo.
- Nasopharyngitis (common cold): 2.9% on Obicetrapib versus 3.0% on placebo.
- Headache: 2.6% on Obicetrapib versus 2.5% on placebo.
- Arthralgia (joint pain): 2.6% on Obicetrapib versus 2.8% on placebo.
- Dizziness: 2.2% on Obicetrapib versus 1.7% on placebo.
- Urinary tract infection: 2.3% on Obicetrapib versus 2.5% on placebo.
Some side effects were reported less frequently in patients taking Obicetrapib compared to placebo, such as upper respiratory tract infection (3.2% on Obicetrapib vs. 3.7% on placebo), hyperglycaemia (2.5% on Obicetrapib vs. 3.5% on placebo), back pain (2.2% on Obicetrapib vs. 2.9% on placebo), and fatigue (2.3% on Obicetrapib vs. 3.8% on placebo).
Clinical Trial Results
Obicetrapib has been studied in several clinical trials to evaluate its effectiveness in managing cholesterol levels and, in one study, its potential impact on markers related to Alzheimer's disease.
Lipid Management Studies
In a randomized study (NCT04753606) evaluating Obicetrapib as an add-on to statin therapy, patients receiving Obicetrapib 10 mg saw significant improvements in their lipid profiles:
- Low-density lipoprotein cholesterol (LDL-C), often called "bad" cholesterol, was reduced by an average of 44% to 47% from baseline, compared to a 5% to 7% reduction in patients taking placebo.
- High-density lipoprotein cholesterol (HDL-C), or "good" cholesterol, increased by an average of 156% to 165%, while placebo patients experienced a decrease of 5% to 7%.
- Apolipoprotein B (ApoB), another marker of cardiovascular risk, decreased by an average of 27% to 30%, versus a 3% to 5% decrease with placebo.
A lower dose of Obicetrapib (5 mg) also showed benefits, reducing LDL-C by 35% to 38%, increasing HDL-C by 122% to 135%, and decreasing ApoB by 22% to 24%.
Another study (NCT04770389) explored Obicetrapib in combination with ezetimibe. Patients receiving the combination therapy experienced an average reduction in LDL-C of 43% to 52% from baseline, compared to a 13% to 15% reduction with ezetimibe alone, and minimal change with placebo. Apolipoprotein B (ApoB) also saw a greater reduction of 30% to 35% with combination therapy, versus 8% to 9% with ezetimibe alone.
The study NCT05266586 further supported the benefits of combination therapy, showing that Obicetrapib 10 mg combined with ezetimibe led to an average reduction in LDL-C of 59% to 63% and ApoB of 35% compared to placebo. Obicetrapib 10 mg alone reduced LDL-C by 39% to 44% and ApoB by 22% to 24%.
In a study (NCT05142722) where Obicetrapib 10 mg was added to existing maximum tolerated lipid-modifying therapies, patients experienced an average reduction in LDL-C of 25% to 30% and an increase in HDL-C of 125% to 137% over 84 to 365 days. Importantly, lipoprotein(a) (Lp(a)), another risk factor for heart disease, was reduced by a median of 32% at day 84, while it increased by 13.65% in the placebo group.
Alzheimer's Disease Related Study
In a proof-of-concept, open-label study (NCT05161715) in patients with early Alzheimer's disease, Obicetrapib 10 mg tablets were investigated for their effect on specific proteins. Patients showed an average increase of 47.8% in Apolipoprotein E (ApoE) in plasma and 3.9% in cerebrospinal fluid (CSF). Apolipoprotein A-I (ApoA-I) in plasma increased by 37.5%, while in CSF it decreased by 8.4%.
Currently Recruiting Trials
Researchers are actively seeking volunteers for several clinical trials investigating Obicetrapib, a potential new medication. These studies aim to understand how Obicetrapib works in the body, its effectiveness for various conditions, and its safety profile. Your participation could contribute significantly to medical knowledge.
One important study, NCT07219602, is a Phase 3 trial evaluating Obicetrapib for individuals with Type 2 Diabetes, Metabolic Syndrome, and other lipid disorders. This study will assess the efficacy, safety, and tolerability of Obicetrapib 10 mg, both alone and in a fixed-dose combination with ezetimibe 10 mg, when added to existing guideline-recommended lipid-lowering therapies. The trial aims to enroll approximately 300 participants.
Another trial, NCT06982508, is a Phase 2 study focused on antioxidant absorption. This research seeks to determine if Obicetrapib 10 mg can alter antioxidant levels in the blood plasma, HDL particles, and retinal tissue of healthy volunteers. This study is designed to include about 100 participants.
Additionally, a Phase 2 open-label trial, NCT06496243, is investigating the impact of Obicetrapib on lipoprotein(a) or Lp(a) levels in patients with dyslipidemias. This study will evaluate the effects of Obicetrapib 10 mg daily, as well as a combination of Obicetrapib with evolocumab (Repatha), on elevated Lp(a). Approximately 69 participants are targeted for enrollment in this trial.
Where to Participate
Clinical trials for Obicetrapib are currently recruiting across a wide geographic area, offering opportunities for participation in many communities. Studies are being conducted at 20 sites across 21 cities in 14 states, making it accessible to a diverse group of volunteers.
Top recruiting locations include:
- Jacksonville, Florida (2 sites)
- La Jolla, California
- Lake City, Florida
- Miami Gardens, Florida
- Miami Lakes, Florida
- Louisville, Kentucky
- Oxon Hill, Maryland
- Jefferson City, Missouri
- Missoula, Montana
- Bridgeton, New Jersey
Eligibility for these trials generally includes individuals between the ages of 18 and 75 years, of all genders. Some studies are specifically seeking healthy volunteers, while others focus on patients with particular health conditions. Children are not eligible to participate in these studies.
Development Timeline
The journey of Obicetrapib in clinical development began with its first trial on February 15, 2021, driven entirely by NewAmsterdam Pharma. Since then, the program has expanded significantly, with a total of 18 clinical trials initiated and an impressive 14,305 participants enrolled across all studies to date.
Initially, research focused on conditions such as IBS-C and hyperphosphatemia. However, the development pipeline quickly broadened to explore Obicetrapib's potential in a wider range of lipid-related and metabolic disorders. This expansion includes studies for dyslipidemias, familial hypercholesterolemia, atherosclerotic cardiovascular disease (ASCVD), and metabolic syndrome (MetS).
The development has progressed through various phases, with 5 trials completed in Phase 1, 7 trials in Phase 2, and 6 trials now in Phase 3, indicating a robust and advancing program. The latest trial is projected to conclude by October 22, 2025, reflecting ongoing commitment to understanding Obicetrapib's full therapeutic potential.