Clinical trial NCT05972278: Investigating the Effect of Obicetrapib on Lipoprotein Metabolism
Official title: A Placebo-Controlled, Phase 1 Study to Investigate the Effect of Obicetrapib on Lipoprotein Metabolism.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Lipid Metabolism
Lead sponsor: NewAmsterdam Pharma
Sponsor class: INDUSTRY
Collaborators: name: University of Pennsylvania
First posted: 2023-08-02
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a phase 1, single-site, double-blind, randomized, placebo-controlled, 2 period, fixed-sequence, pharmacodynamic study in healthy participants meeting the eligibility requirements. Participants will be randomized in a 1:1 ratio to either obicetrapib or matching placebo, and evenly distributed between treatment groups based on their Screening Lp(a) values; ≥ 30 mg/dL vs \< 30 mg/dL. LDL-C levels ≥ 100 mg/dL and ≤ 190 mg/dL have been selected for this study as the target population as this is the population of patients targeted for treatment with obicetrapib as an adjunct to statin therapy.
Primary purpose: TREATMENT

Brief summary: To determine the treatment effect with obicetrapib (10 mg) on the fractional catabolic rate (FCR) of apolipoprotein (apo) B100 in low-density lipoprotein (LDL).

Detailed description: The study population will comprise 20 adults, 18 to 75 years of age, with LDL-C level ≥ 100 and ≤ 190 mg/dL, and in generally good health.

Eligibility criteria: Inclusion Criteria:

* Willing to sign the Informed Consent Form.
* Male or female between 18 to 75 years of age.
* Females may be enrolled if they are not pregnant, are not breastfeeding, and do not plan on becoming pregnant during the study.
* Stable weight (± 3 kg) for at least 6 weeks prior to screening.
* Body mass index (BMI) of \> 18.5 and ≤ 40 kg/m2 at Screening. BMI is calculated by taking the participants weight in kg and dividing it by the height in meters, squared.
* Participant 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 Screening and/or prior to administration of the initial dose of study drug.
* Fasting plasma triglyceride level ≤ 400 mg/dL at Screening.
* LDL-C level of ≥ 100 mg/dL and ≤ 190 mg/dL at Screening.

Exclusion Criteria:

* Has taken or plans to take any lipid-lowering medications or medications known to alter lipoprotein metabolism within 4 weeks of Screening, (e.g. statins, fibrates, niacin, cholesterol absorption inhibitors, bile acid-sequestrants, fish oils, PCSK9 inhibitors, red yeast rice, glucocorticoids, and anabolic agents).
* Current, or any previous history of New York Heart Association (NYHA) class III or IV heart failure or left ventricular ejection fraction \< 30%.
* 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 participant may be randomized.
* HDL-C \> 60 mg/dL if male or \>70 mg/dL if female, at Screening.
* An eGFR \< 45 mL/min/1.73m2 at the Screening visit or history of end-stage renal disease (ESRD).
* 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) \> 2 x upper limit of normal (ULN); or total bilirubin \> 2 x ULN at the and/or Screening visit.
* History of stroke, chronic seizures, or major neurological disorder.
* Participants 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 a change in thyroid hormone therapy is recommended, or if this represents a new diagnosis, then the participant is not eligible. Note: Hypothyroidism is defined as having a TSH \> 20% above the local laboratory's upper limit of the normal reference range. One redraw will be allowed if the original TSH value is equal to or less than 40% above the normal reference range at the local laboratory. The participant must meet his criterion upon redraw.
* Participant with a history of neoplastic disease. Note: Participant treated non-melanoma skin carcinoma, and other malignancies which have been successfully treated ≥ 5 years prior to the Screening visit where, in the judgment of both the PI and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of the Screening visit.
* Has participated in another investigational drug study within 30 days of Screening

Primary outcomes:
measure: Treatment with obicetrapib (10 mg) on the fractional catabolic rate (FCR) of apolipoprotein (apo) B100 in low-density lipoprotein (LDL).
timeFrame: 8-12 week
Secondary outcomes:
measure: Treatment with obicetrapib (10 mg) on the production rate (PR) of apolipoprotein(a), or apo(a), in Lp(a).
timeFrame: 8-12 weeks
Other outcomes:
measure: Treatment with obicetrapib (10 mg) on the FCR of total apolipoprotein (apo) B100 in plasma.
timeFrame: 8-12 weeks
Locations:
city: Philadelphia
country: United States
facility: Archna Bajaj, MD
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Archna Bajaj, MD
role: PRINCIPAL_INVESTIGATOR
References: