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

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the pharmacokinetics (PK) of a single dose of olpasiran in participants with normal renal function and participants with various degrees of renal impairment.

Official Title
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A Phase I, Open-label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Pharmacodynamics of Olpasiran in Subjects With Normal Renal Function and Subjects With Various Degrees of Renal Impairment

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: Olpasiran


Participation Criteria
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Eligibility Criteria
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Inclusion: Male participants or female participants of nonchildbearing potential between 18 and 75 years of age (inclusive) at the time of Screening. Body mass index between 18 and 40 kg/m^2 (inclusive) at the time of Screening. Eligible participants classified based on established need for renal replacement therapy and eGFR at Screening. Assignment will be based on eGFR at Screening. Group 1 (Normal): eGFR ≥ 90 mL/min and no history of renal disease. Group 2 (Mild): 60 ≤ eGFR ≤ 89 mL/min. Group 3 (Moderate): 30 ≤ eGFR ≤ 59 mL/min. Group 4 (Severe): 15 ≤ eGFR ≤ 29 mL/min without dialysis. Group 5 (Kidney Failure): eGFR < 15 mL/min and dialysis patients (off-dialysis). Group 6 (Kidney Failure): eGFR < 15 mL/min and dialysis patients (on-dialysis). Exclusion: Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase or alanine aminotransferase > 2 times the upper limit of normal. Clinically significant hyperkalemia (defined by serum potassium concentration as > 5.5 mEq/L for Groups 1 to 4, > 6 mEq/L for Groups 5 and 6) at Screening or Check-in. History of hypersensitivity, intolerance, or allergy to any drug compound, or other substance, unless approved by the Investigator (or designee) and in consultation with the Sponsor. Female participants with a positive pregnancy test at Screening or Check-in. Participant has received a dose of an investigational drug within the past 30 days or 5 halflives, whichever is longer, prior to Check-in. Participants in Group 1 only (participants with normal renal function) are excluded if: • A history of renal disease or renal injury as indicated by medical history or an abnormal renal function profile at Screening or Check-in. Participants in Groups 2 to 6 (participants with varying degrees of renal impairment) are excluded if: • A change in disease status within 30 days of Screening, as documented by the participant's medical history, deemed clinically significant by the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Dose Olpasiran Renal Impairment<br>Participants will be enrolled in 1 of 5 renal function groups based on their renal impairment status, as determined by estimated glomerular filtration rate (eGFR). All participants will receive a single dose of olpasiran on Day 1. | Drug: Olpasiran<br>* Participants will receive olpasiran by subcutaneous (SC) injection.<br>* Other names: AMG 890;|
| Experimental: Single Dose Olpasiran Normal Renal Function<br>Participants with normal renal function will be enrolled and will receive a single dose of olpasiran on Day 1. | Drug: Olpasiran<br>* Participants will receive olpasiran by subcutaneous (SC) injection.<br>* Other names: AMG 890;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Dialysis Clearance of Drug From Plasma (CLD) of Olpasiran |  | Pre-Dialysis, 0.5, 1, 3 hours after the start of Dialysis, and immediately following the end of Dialysis, Day 1, Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 in 12-lead Electrocardiogram (ECG) Measurements |  | Up to Day 85 | 
| Number of Participants with Clinically Significant Changes in Vital Signs |  | Up to Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Olpasiran, Renal Impairment, Normal Renal Function, AMG 890