Clinical trial NCT05489614: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Olpasiran
Renal Impairment
Normal Renal Function
AMG 890
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2022-08-05
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Olpasiran
timeFrame: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
measure: Area Under the Plasma Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Olpasiran
timeFrame: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
measure: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Olpasiran
timeFrame: Predose, 0.5, 1, 3, 6, 9, 12, 24, 36, 48, 72, 96, 144 hours (postdose), Day 15, and Day 29
measure: Dialysis Clearance of Drug From Plasma (CLD) of Olpasiran
timeFrame: Pre-Dialysis, 0.5, 1, 3 hours after the start of Dialysis, and immediately following the end of Dialysis, Day 1, Day 4
Secondary outcomes:
measure: Area Under the Effect Time Curve (AUEC) of Plasma Lipoprotein a (Lp[a])
timeFrame: Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
measure: Maximum Inhibitory Effect (Imax) of Plasma Lp(a)
timeFrame: Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
measure: Time to Reach Imax of Lp(a)
timeFrame: Screening, Day 1, Day 2, Day 4, Day 7, Day 15, Day 29, Day 57, and Day 85
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to Day 85
measure: Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations
timeFrame: Up to Day 85
measure: Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Measurements
timeFrame: Up to Day 85
measure: Number of Participants with Clinically Significant Changes in Vital Signs
timeFrame: Up to Day 85
Other outcomes:
Locations:
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC
state: California
city: Yucaipa
country: United States
facility: CRSCA HC LLC, dba Creekside Post Acute
state: California
city: Miami
country: United States
facility: Clinical Pharmacology Of Miami, LLC
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Saint Paul
country: United States
facility: Nucleus Network - Minneapolis
state: Minnesota
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: