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

Amgen

Status and phase: Completed; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Olpasiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT05481411

20220009

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts 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).

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 2 patient groups

Single Dose Olpasiran Hepatic Impairment

Experimental group

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.

Treatment:

Drug: Olpasiran

Single Dose Olpasiran Normal Hepatic Function

Experimental group

Description:

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

Treatment:

Drug: Olpasiran