search
Back to results

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

Primary Purpose

Hepatic Impairment

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Olpasiran
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hepatic Impairment focused on measuring Olpasiran, Hepatic Impairment, Normal Hepatic Function, AMG 890

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

  • Inland Empire Clinical Trials, LLC
  • Orlando Clinical Research Center
  • The Texas Liver Institute, Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Single Dose Olpasiran Hepatic Impairment

Single Dose Olpasiran Normal Hepatic Function

Arm Description

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.

Participants with normal hepatic function will be enrolled and will receive a single dose of olpasiran on Day 1.

Outcomes

Primary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of Olpasiran
Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Olpasiran
Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Olpasiran

Secondary Outcome Measures

Area Under the Effect Time Curve (AUEC) of Plasma Lipoprotein a (Lp[a])
Maximum Inhibitory Effect (Imax) of Plasma Lp(a)
Time to Reach Imax of Lp(a)
Number of Participants Who Experience an Adverse Event (AE)
Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations
Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements
Number of Participants with Clinically Significant Changes in Vital Signs

Full Information

First Posted
July 28, 2022
Last Updated
September 20, 2023
Sponsor
Amgen
search

1. Study Identification

Unique Protocol Identification Number
NCT05481411
Brief Title
A Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Participants With Various Degrees of Hepatic Impairment
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
September 13, 2022 (Actual)
Primary Completion Date
April 5, 2023 (Actual)
Study Completion Date
May 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Olpasiran, Hepatic Impairment, Normal Hepatic Function, AMG 890

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Dose Olpasiran Hepatic Impairment
Arm Type
Experimental
Arm Description
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.
Arm Title
Single Dose Olpasiran Normal Hepatic Function
Arm Type
Experimental
Arm Description
Participants with normal hepatic function will be enrolled and will receive a single dose of olpasiran on Day 1.
Intervention Type
Drug
Intervention Name(s)
Olpasiran
Other Intervention Name(s)
AMG 890
Intervention Description
Subcutaneous injection
Primary Outcome Measure Information:
Title
Maximum Observed Serum Concentration (Cmax) of Olpasiran
Time Frame
Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Title
Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Olpasiran
Time Frame
Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Title
Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Olpasiran
Time Frame
Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Secondary Outcome Measure Information:
Title
Area Under the Effect Time Curve (AUEC) of Plasma Lipoprotein a (Lp[a])
Time Frame
Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
Title
Maximum Inhibitory Effect (Imax) of Plasma Lp(a)
Time Frame
Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
Title
Time to Reach Imax of Lp(a)
Time Frame
Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
Title
Number of Participants Who Experience an Adverse Event (AE)
Time Frame
Up to Day 85
Title
Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations
Time Frame
Up to Day 85
Title
Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements
Time Frame
Up to Day 85
Title
Number of Participants with Clinically Significant Changes in Vital Signs
Time Frame
Up to Day 85

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Inland Empire Clinical Trials, LLC
City
Rialto
State/Province
California
ZIP/Postal Code
92377
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
The Texas Liver Institute, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
http://www.amgen.com/datasharing
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

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

We'll reach out to this number within 24 hrs