Investigating the Effect of Obicetrapib on Lipoprotein Metabolism

A Placebo-Controlled, Phase 1 Study to Investigate the Effect of Obicetrapib on Lipoprotein Metabolism.

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

Study Overview

• Status: Recruiting
• Conditions: Lipid Metabolism
• Intervention / Treatment: Drug: Obicetrapib

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Archna Bajaj, MD; Phone Number: +1 215-662-7197; Email: abajaj@pennmedicine.upenn.edu
• Study Contact Backup: Name: Karen Terembula; Email: kterembu@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Archna Bajaj, MD
      • Contact: John Millar, PhD; Email: jsmillar@pennmedicine.upenn.edu
      • Principal Investigator: Archna Bajaj, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Obicetrapib placebo; identical matching placebo	Drug: Obicetrapib; 1 tablet daily; Other Names: tablets
Experimental: Obicetrapib 10 mg; 10 mg tablets	Drug: Obicetrapib; 1 tablet daily; Other Names: tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment with obicetrapib (10 mg) on the fractional catabolic rate (FCR) of apolipoprotein (apo) B100 in low-density lipoprotein (LDL).	The mean differences (obicetrapib - placebo) in the LDL apoB100 FCR using the baseline measure (no study treatment) compared to the LDL apoB100 FCR of each variable following the Treatment Period.	8-12 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment with obicetrapib (10 mg) on the production rate (PR) of apolipoprotein(a), or apo(a), in Lp(a).	The mean differences (obicetrapib - placebo) in the apo(a) in Lp(a) production rate using the baseline measure (no treatment) compared to the apo(a) PR obtained following the Treatment Period.	8-12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment with obicetrapib (10 mg) on the FCR of total apolipoprotein (apo) B100 in plasma.	The mean difference (obicetrapib - placebo) on the FCR of total apolipoprotein (apo) B100 in plasma using the baseline measure (no treatment) compared to the FCR of apoliprotien (apo) B100 following the Treatment Period.	8-12 weeks

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma
• Collaborators: University of Pennsylvania
• Investigators: Principal Investigator: Archna Bajaj, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 2, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 20, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias
• Other Study ID Numbers: TA-8995-204; The NICE Study (Other Identifier: NewAmsterdam Pharma)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No