Clinical trial NCT05481411: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Olpasiran
Hepatic Impairment
Normal Hepatic Function
AMG 890
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-08-01
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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).

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Olpasiran
timeFrame: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
measure: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Olpasiran
timeFrame: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
measure: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Olpasiran
timeFrame: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
Secondary outcomes:
measure: Area Under the Effect Time Curve (AUEC) of Plasma Lipoprotein a (Lp[a])
timeFrame: Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
measure: Maximum Inhibitory Effect (Imax) of Plasma Lp(a)
timeFrame: Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
measure: Time to Reach Imax of Lp(a)
timeFrame: Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to Day 85
measure: Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations
timeFrame: Up to Day 85
measure: Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements
timeFrame: Up to Day 85
measure: Number of Participants with Clinically Significant Changes in Vital Signs
timeFrame: Up to Day 85
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC
state: California
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: San Antonio
country: United States
facility: The Texas Liver Institute, Inc.
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: