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

Renal Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05489614
• Other study ID #: 20220010
• Status: Completed
• Phase: Phase 1
• Start date: September 13, 2022
• Est. completion date: December 19, 2023

Study information

• Verified date: January 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 19, 2023
• Est. primary completion date: October 24, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Olpasiran
Participants will receive olpasiran by subcutaneous (SC) injection.

Locations

Country	Name	City	State
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Clinical Pharmacology Of Miami, LLC	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Inland Empire Clinical Trials, LLC	Rialto	California
United States	Nucleus Network - Minneapolis	Saint Paul	Minnesota
United States	CRSCA HC LLC, dba Creekside Post Acute	Yucaipa	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Number of Participants Who Experience an Adverse Event (AE)		Up to Day 85
Secondary	Number of Participants with Clinically Significant Changes in Clinical Laboratory Evaluations		Up to Day 85
Secondary	Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Measurements		Up to Day 85
Secondary	Number of Participants with Clinically Significant Changes in Vital Signs		Up to Day 85

External Links

•   AmgenTrials clinical trials website