Hepatic Impairment
Conditions
Keywords
Olpasiran, Hepatic Impairment, Normal Hepatic Function, AMG 890
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.
Interventions
DRUGOlpasiran
Subcutaneous injection
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
United States
Outcome results
None listed