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 Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single Dose Olpasiran Renal Impairment 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
Participants will receive olpasiran by subcutaneous (SC) injection.
Other Names:
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| Experimental: Single Dose Olpasiran Normal Renal Function Participants with normal renal function will be enrolled and will receive a single dose of olpasiran on Day 1. |
Drug: Olpasiran
Participants will receive olpasiran by subcutaneous (SC) 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]
- 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
- 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]
Eligibility Criteria
Criteria
Inclusion:
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Male participants 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 and 40 kg/m^2 (inclusive) at the time of Screening.
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Eligible participants classified based on established need for renal replacement therapy and eGFR at Screening. Assignment will be based on eGFR at Screening.
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Group 1 (Normal): eGFR ≥ 90 mL/min and no history of renal disease.
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Group 2 (Mild): 60 ≤ eGFR ≤ 89 mL/min.
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Group 3 (Moderate): 30 ≤ eGFR ≤ 59 mL/min.
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Group 4 (Severe): 15 ≤ eGFR ≤ 29 mL/min without dialysis.
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Group 5 (Kidney Failure): eGFR < 15 mL/min and dialysis patients (off-dialysis).
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Group 6 (Kidney Failure): eGFR < 15 mL/min and dialysis patients (on-dialysis).
Exclusion:
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Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase or alanine aminotransferase > 2 times the upper limit of normal.
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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.
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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.
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Female participants with a positive pregnancy test at Screening or Check-in.
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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.
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.- 20220010