Investigating the Effect of Obicetrapib on Lipoprotein Metabolism
Study Details
Study Description
Brief Summary
To determine the treatment effect with obicetrapib (10 mg) added to background statin therapy on the fractional catabolic rate (FCR) of apolipoprotein (apo) B100 in low-density lipoprotein (LDL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study population will comprise 20 adults, 18 to 75 years of age, who are either normolipidemic or dyslipidemic and in good health otherwise based on medical history, physical examination, vital signs and laboratory safety tests. Subjects will have plasma triglyceride level ≤ 400 mg/dL and LDL-cholesterol (LDL-C) levels ≥ 70 mg/dL and ≤ 200 mg/dL at Screening Visit and on stable Atorvastatin or Rosuvastatin for a minimum of 4 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Obicetrapib placebo identical matching placebo |
Drug: Obicetrapib
1 tablet daily
Other Names:
|
| Experimental: Obicetrapib 10 mg 10 mg tablets |
Drug: Obicetrapib
1 tablet daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Treatment with obicetrapib (10 mg) added to background statin therapy on the fractional catabolic rate (FCR) of apolipoprotein (apo) B100 in low-density lipoprotein (LDL). [8-12 week]
The difference in LDL apoB100 FCR obtained following Period 1 (statin alone) compared to the LDL apoB100 FCR obtained following Period 2 (obicetrapib + statin).
Secondary Outcome Measures
- Treatment with obicetrapib (10 mg) added to background statin therapy on the production rate (PR) of apolipoprotein(a), or apo(a), in Lp(a). [8-12 weeks]
The difference in apo(a) PR obtained following Period 1 (statin alone) compared to the apo(a) PR obtained following Period 2 (obicetrapib + statin).
Other Outcome Measures
- Treatment with obicetrapib (10 mg) added to background statin therapy on the PR of LDL apoB100. [8-12 weeks]
The difference in the total apoB100 FCR obtained following Period 1 (statin alone) compared to the total apoB100 FCR obtained following Period 2 (obicetrapib + statin).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willing to sign the Informed Consent Form.
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Subject is a male or female between 18 to 75 years of age.
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Females may be enrolled if they are not pregnant, are not breastfeeding, and do not plan on becoming pregnant during the study.
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Subject has a stable weight (± 3 kg) for at least 6 weeks prior to screening.
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Subject has a body mass index (BMI) of > 18.5 and ≤ 40 kg/m2 at the pre-study (Screening) visit. BMI is calculated by taking the subject's weight in kg and dividing it by the subject's height in meters, squared.
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Subject is judged to be in good health by the Study PI based on medical history, physical examination, vital sign measurements, electrocardiogram (ECG) assessments and laboratory safety tests performed at the Screening (Visit 1A) and/or prior to administration of the initial dose of study drug.
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Subject has fasting plasma triglyceride level ≤ 400 mg/dL, at Screening Visit 1A and is on atorvastatin or rosuvastatin for a minimum of 4 weeks, or at the Statin Optimization Visit 1B if subject has switched to, or initiated, 10 mg daily rosuvastatin for a minimum of 4 weeks.
Exclusion Criteria:
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Subject is statin-naïve and has an LDL-C < 110 mg/dL at Screening (Visit 1A).
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Subject has a current or any previous history of New York Heart Association (NYHA) class III or IV heart failure or left ventricular ejection fraction < 30%.
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Subject has uncontrolled hypertension defined as either systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg prior to the Baseline visit, taken as the average of triplicate measurements. One triplicate retest will be allowed during the same visit, at which point if the retest result is no longer exclusionary, the subject may be randomized.
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Subject has an eGFR < 45 mL/min/1.73m2 at the Screening visit or history of end-stage renal disease (ESRD).
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Subject has active liver disease, defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN); or total bilirubin > 2 x ULN at the and/or Screening visit.
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Subject has a history of stroke, chronic seizures, or major neurological disorder.
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For subjects on thyroid hormone replacement treatment at the time of screening, there is no lower thyroid stimulating hormone (TSH) threshold for entry. The subject must have been on a stable dose of thyroid hormone therapy for ≥ 6 weeks prior to the screening. If TSH levels are undetectable and the subject requires a change in thyroid hormone therapy or this represents a new diagnosis, then the subject will be excluded.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- NewAmsterdam Pharma
- University of Pennsylvania
Investigators
- Study Chair: Dan Radar, MD, University of Pennsylvania
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TA-8995-204
- The NICE Study