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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06048302
• Other study ID #: TA-8995-12
• Status: Recruiting
• Phase: Phase 1
• Start date: November 30, 2023
• Est. completion date: July 30, 2024

Study information

• Verified date: August 2023
• Source: NewAmsterdam Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: July 30, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 (ß-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.

Related Conditions & MeSH terms

• Healthy
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Obicetrapib
1 single dose of obicetrapib

Locations

Country	Name	City	State
United States	Nucleus Network	Saint Paul	Minnesota
United States	The American Research Corporation	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
NewAmsterdam Pharma	Veranex

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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