PK and Safety in Participants Taking Obicetrapib With Moderate Hepatic Impairment Relative to Normal Hepatic Function

A Phase 1, Open-label, Single-dose, Parallel-group Study to Evaluate the Plasma Pharmacokinetics and Safety of Obicetrapib in Participants With Moderate Hepatic Impairment Relative to Participants With Normal Hepatic Function

To investigate the safety and pharmacokinetics in patients with moderate hepatic impairment compared to healthy participants after a single oral dose of obicetrapib (10 mg).

Study Overview

• Status: Recruiting
• Conditions: Healthy; Hepatic Impairment
• Intervention / Treatment: Drug: Obicetrapib

Detailed Description

This is a Phase 1, open-label, single-dose, parallel-group study to evaluate the plasma PK and safety of obicetrapib in participants with moderate hepatic impairment relative to participants with normal hepatic function. The purpose of the study is to investigate the effect of moderate hepatic impairment on obicetrapib PK and safety in otherwise healthy participants after a single oral 10 mg dose of obicetrapib.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Recruiting
      • Nucleus Network
      • Contact: Jennifer Bookley; Phone Number: 651-641-2900; Email: Trisha Shamp <t.shamp@nucleusnetwork.com>
  • Texas
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • The American Research Corporation
      • Contact: Haylee Schulmeier; Phone Number: 210-253-3426; Email: hschulmeier@txliver.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• A male or a female of non-childbearing potential.
• Women of childbearing potential (WOCBP) must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at the Screening Visit.
• Body mass index (BMI) of 17.5 to 42 kg/m2; with a total body weight >50 kg (110 lb).
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Cohort 1: Meet the criteria for Class B (moderate hepatic impairment) of the modified CPC. A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination (PE), liver biopsy, hepatic ultrasound, computerized tomography scan, or magnetic resonance imaging.
• Cohort 2: Will only enroll healthy volunteers with no hepatic impairment. "Healthy" is defined as no clinically relevant abnormalities identified by a detailed medical history, complete PE (including blood pressure [BP] and pulse rate measurement), 12-lead ECG or clinical laboratory tests performed during Screening.

Exclusion Criteria:

• Any condition possibly affecting drug absorption (e.g., gastrectomy). Uncomplicated cholecystectomy is allowed.
• History of or current positive results for human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) or hepatitis C virus (HCV), including hepatitis B surface antigen (HbsAg) or hepatitis C Virus antibody (HCVAb).
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the Investigator's judgment, make the participant inappropriate for participation in the study.
• Participants with an estimated glomerular filtration rate (eGFR) value of ≤30 mL/min/1.73 m2, based on the 2021 Chronic Kidney Disease Epidemiology Collaboration equation during Screening. A single repeat assessment is permitted to assess eligibility, if needed.
• Previous administration of drugs or supplements known to be strong inducers or inhibitors of CYP3A4 within 7 days of planned dosing of obicetrapib on Day 1.
• Concurrent use of drugs or supplements that are known substrates of CYP3A that have narrow therapeutic indices (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl including transdermal patch, pimozide, quinidine, sirolimus, tacrolimus) within 12 days prior to planned dosing of obicetrapib on Day 1.
• Participants on oral contraceptives and hormonal based contraceptives including implantable, intrauterine, intravaginal, transdermal or injectable form.
• Previous administration of an investigational drug within 30 days (or as determined by the local requirement) or within 5 half-lives of that investigational drug, prior to planned dosing of obicetrapib on Day 1.
• Known hypersensitivity to obicetrapib or its excipients.
• A positive urine drug test. Participants with moderate hepatic impairment (Cohort 1) will be eligible to participate if their urine drug test is positive with a drug for a prescribed condition that is not expected to interfere with the PK of obicetrapib. Positive urine drug tests for tetrahydrocannabinol (THC) will be allowed as long as the volunteer agrees to abstain from ingesting any THC-containing products for the duration of the study (including Out patient visits up to Day 28).
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to planned dosing of obicetrapib on Day 1.
• History of sensitivity to heparin or a history of heparin-induced thrombocytopenia.
• Unwilling or unable to comply with the criteria in the Lifestyle considerations listed in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Comparitor: Subjects with Moderate Hepatic Impairment; 8 patients with hepatic impairment of moderate Child Pugh Category	Drug: Obicetrapib; 1 single dose of obicetrapib; Other Names: 10 mg tablet
Other: Active Comparator: Healthy Subjects; Healthy volunteers will be matched with impaired hepatic function patients	Drug: Obicetrapib; 1 single dose of obicetrapib; Other Names: 10 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve from dosing time to infinity (AUC (0-inf)) for obicetrapib	Blood samples collected	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168
Area under curve from dosing time to last measurement (AUC (0-t)) for obicetrapib	Blood Sample Collected	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168
Observed maximum plasma concentration (Cmax) for Obicetrapib	Blood Sample Collected	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168

Collaborators and Investigators

• Sponsor: NewAmsterdam Pharma
• Collaborators: Veranex

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2023
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): July 30, 2024

Study Registration Dates

• First Submitted: August 29, 2023
• First Submitted That Met QC Criteria: September 15, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 20, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: TA-8995-12

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