A Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Participants With Various Degrees of Hepatic Impairment

A Phase I, Open-label Single Dose Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Subjects With Various Degrees of Hepatic Impairment

The primary objective of the study is to evaluate the pharmacokinetics (PK) of a single dose of olpasiran in participants with mild, moderate, or severe hepatic impairment compared to participants with normal hepatic function.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Olpasiran

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials, LLC
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • The Texas Liver Institute, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female participants of nonchildbearing potential, between 18 and 75 years of age (inclusive) at the time of Screening.
• Body mass index between 18.0 and 40.0 kg/m^2 (inclusive) at the time of Screening.

Participants with Normal Hepatic Function Only:

• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations at Screening and Check-in as assessed by the Investigator (or designee).

Participants with Hepatic Impairment Only:

• Child-Pugh A (Group 2), B (Group 3), or C (Group 4) classification defined by both Screening (to determine participant group) and Check-in (to confirm participant group prior to dosing) clinical laboratory values and physical examination findings.

Exclusion Criteria:

• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• Estimated glomerular filtration rate < 60 mL/min/1.73m^2 (Groups 1-3) or < 50 mL/min/1.73m^2 (Group 4 only) by Modification of Diet in Renal Disease formula at Screening or Check-in.
• Receiving or has received any investigational drug within the 30 days or 5 half-lives (whichever is longer) before receiving olpasiran.
• Participants who were previously exposed to olpasiran.
• Female participants with a positive pregnancy test at Screening or Check-in.

Participants with Normal Hepatic Function Only:

• Positive hepatitis panel. Participants whose results are compatible with prior immunization may be included.
• Alanine aminotransferase and aspartate aminotransferase elevations > 3x upper limit of normal at Screening or Check-in.

Participants with Hepatic Impairment Only:

• Positive for hepatitis B surface antigen. Participants with positive hepatitis B core antibody may be included if hepatitis B surface antigen is negative. Participants with positive hepatitis B surface antibody may be included (consistent with prior vaccination).
• Active malignancy of any type. Participants with a history of malignancy that has been eradicated with supporting medical documentation indicating that there is no residual malignancy detected in the past 2 years will be allowed.
• Values outside the normal range for liver function tests that are not consistent with their hepatic condition, as determined by the Investigator (or designee).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Dose Olpasiran Hepatic Impairment; Participants will be enrolled in 1 of 3 hepatic impairment groups based on their hepatic impairment status, as determined by Child-Pugh classification. All participants will receive a single dose of olpasiran on Day 1.	Drug: Olpasiran; Subcutaneous injection; Other Names: AMG 890
Experimental: Single Dose Olpasiran Normal Hepatic Function; Participants with normal hepatic function will be enrolled and will receive a single dose of olpasiran on Day 1.	Drug: Olpasiran; Subcutaneous injection; Other Names: AMG 890

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Serum Concentration (Cmax) of Olpasiran	Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Olpasiran	Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Olpasiran	Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Effect Time Curve (AUEC) of Plasma Lipoprotein a (Lp[a])	Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
Maximum Inhibitory Effect (Imax) of Plasma Lp(a)	Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
Time to Reach Imax of Lp(a)	Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
Number of Participants Who Experience an Adverse Event (AE)	Up to Day 85
Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations	Up to Day 85
Number of Participants with Clinically Significant Changes in Vital Signs	Up to Day 85
Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements	Up to Day 85

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2022
• Primary Completion (Actual): April 5, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): August 1, 2022

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 14, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Hepatic Impairment; Olpasiran; AMG 890; Normal Hepatic Function
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; olpasiran
• Other Study ID Numbers: 20220009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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