A Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Participants With Various Degrees of Hepatic Impairment
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single Dose Olpasiran Hepatic Impairment 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. |
Drug: Olpasiran
Subcutaneous injection
Other Names:
|
| Experimental: Single Dose Olpasiran Normal Hepatic Function Participants with normal hepatic function will be enrolled and will receive a single dose of olpasiran on Day 1. |
Drug: Olpasiran
Subcutaneous injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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]
- 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]
Secondary Outcome Measures
- 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]
- 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]
- 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]
- Number of Participants With Clinically Significant Changes 12-lead Electrocardiogram (ECG) Measurements [Up to Day 85]
- Number of Participants with Clinically Significant Changes in Vital Signs [Up to Day 85]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female participants of nonchildbearing potential, between 18 and 75 years of age (inclusive) at the time of Screening.
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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).
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Estimated glomerular filtration rate < 60 mL/min/1.73m2 (Groups 1-3) or < 50 mL/min/1.73m2 (Group 4 only) by Modification of Diet in Renal Disease formula at Screening or Check-in.
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Receiving or has received any investigational drug within the 30 days or 5 half-lives (whichever is longer) before receiving olpasiran.
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Participants who were previously exposed to olpasiran.
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Female participants with a positive pregnancy test at Screening or Check-in.
Participants with Normal Hepatic Function Only:
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Positive hepatitis panel. Participants whose results are compatible with prior immunization may be included.
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Alanine aminotransferase and aspartate aminotransferase elevations > 3x upper limit of normal at Screening or Check-in.
Participants with Hepatic Impairment Only:
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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).
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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.
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Values outside the normal range for liver function tests that are not consistent with their hepatic condition, as determined by the Investigator (or designee).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20220009