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

Amgen

Status and phase: Completed; Phase 1

Conditions: Renal Impairment

Treatments: Drug: Olpasiran

Study type: Interventional

Funder types: Industry

Identifiers

NCT05489614

20220010

Details and patient eligibility

About

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.

Enrollment: 33 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

  1. Group 1 (Normal): eGFR ≥ 90 mL/min and no history of renal disease.
  2. Group 2 (Mild): 60 ≤ eGFR ≤ 89 mL/min.
  3. Group 3 (Moderate): 30 ≤ eGFR ≤ 59 mL/min.
  4. Group 4 (Severe): 15 ≤ eGFR ≤ 29 mL/min without dialysis.
  5. Group 5 (Kidney Failure): eGFR < 15 mL/min and dialysis patients (off-dialysis).
  6. 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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 2 patient groups

Single Dose Olpasiran Renal Impairment

Experimental group

Description:

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.

Treatment:

Drug: Olpasiran

Single Dose Olpasiran Normal Renal Function

Experimental group

Description:

Participants with normal renal function will be enrolled and will receive a single dose of olpasiran on Day 1.

Treatment:

Drug: Olpasiran