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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05481411
• Other study ID #: 20220009
• Status: Completed
• Phase: Phase 1
• Start date: September 13, 2022
• Est. completion date: May 31, 2023

Study information

• Verified date: September 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: May 31, 2023
• Est. primary completion date: April 5, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Olpasiran
Subcutaneous injection

Locations

Country	Name	City	State
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Inland Empire Clinical Trials, LLC	Rialto	California
United States	The Texas Liver Institute, Inc.	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Number of Participants Who Experience an Adverse Event (AE)		Up to Day 85
Secondary	Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations		Up to Day 85
Secondary	Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements		Up to Day 85
Secondary	Number of Participants with Clinically Significant Changes in Vital Signs		Up to Day 85

External Links

•   AmgenTrials clinical trials website