A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Olpasiran in Chinese Participants With Elevated Serum Lipoprotein(a)

Phase 1

Completed

Conditions: Elevated Serum Lipoprotein(a)

Interventions: Drug: Olpasiran

Registration Number: NCT04987320

Lead Sponsor: Amgen

Brief Summary: The main objective of this study is to evaluate the pharmacokinetics (PK) of a single dose of Olpasiran in Chinese participants with elevated serum lipoprotein(a) (Lp\[a\]).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Inclusion eligibility criteria will be evaluated in 2 parts during the screening period:

Part 1: After written informed consent is obtained, subjects will provide a blood sample for a preliminary Lp(a) assessment to determine eligibility for Part 2 screening. Subjects with Lp(a) ≥ 70 nmol/L (or approximately ≥ 27 mg/dL) will be eligible to return to the CRU Part 2 screening. Subjects not eligible to return for Part 2 screening will be screen failed.
Part 2: Eligible subjects will complete all remaining screening procedures and tests that establish eligibility within 40 days prior to the Day 1 visit.

Part 1:

Must be a resident in mainland China, Hong Kong, or Taiwan, and of Chinese Ancestry.
Male or female subjects, between 18 and 60 years of age (inclusive) at the time of Screening.
Screening serum Lp(a) ≥ 70 nmol/L (or approximately ≥ 27 mg/dL).

Part 2:

In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [e.g., suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) as assessed by the Investigator (or designee).
Body mass index between 18 and 32 kg/m^2 (inclusive) at the time of Screening.
Subjects who are on statin must be on a stable dose of the same statin for at least 6 weeks prior to enrollment, and plan to remain on a stable dose (i.e., no change in medication or dosage) for the duration of the study.
Females must be of non-reproductive potential:

a. Postmenopausal defined as: i. Age of ≥ 55 years with no menses for at least 12 months; OR ii. Age of < 55 years with no menses for at least 12 months AND with a follicle stimulating hormone (FSH) level > 40 IU/L or according to the definition of "postmenopausal range" for the laboratory involved; OR b. History of hysterectomy; OR c. History of bilateral oophorectomy.

Exclusion Criteria

History or clinical evidence of peripheral neuropathy.
Currently receiving apheresis as lipid reducing therapy.
History or clinical evidence of bleeding diathesis or any coagulation disorder, including prothrombin time (PT), activated partial thromboplastin time (APTT), or platelet count outside of the laboratory's normal reference range at screening. Subjects with PT and/or APTT values that are outside of the laboratory's normal reference range at screening may still be eligible to proceed to enrollment if the results are judged by the investigator in consultation with the study medical monitor to not be clinically significant.
History or clinical evidence of diabetes mellitus, including a fasting glucose ≥ 125 mg/dL (6.9 mmol/L) at Screening.
Use of any herbal medicines, vitamins or dietary supplements known to affect lipid metabolism (e.g. sigh oils > 100mg/day, red yeast extract), within 30 days prior to dosing on Day 1 and for the duration of the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Olpasiran Dose B	Olpasiran	Participants will be administered Olpasiran dose B as a subcutaneous injection.
Olpasiran Dose A	Olpasiran	Participants will be administered Olpasiran dose A as a subcutaneous injection.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Concentration (Cmax) of Olpasiran	Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85	The serum pharmacokinetic (PK) parameters of olpasiran were calculated using standard noncompartmental methods.

Secondary Outcome Measures

Name	Time	Method
Apparent Terminal Elimination Half-life (T1/2) of Olpasiran	Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85	The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.
Apparent Total Body Clearance (CL/F) of Olpasiran	Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85	The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.
Area Under the Serum Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Olpasiran	Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85	The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.
Percentage Change From Baseline in Triglycerides	Baseline and Days 7, 15, 57, 155 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.
Time to Cmax (Tmax) of Olpasiran	Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85	The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.
Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Olpasiran	Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85	The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.
Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Olpasiran	Predose, 30 and 60 minutes, 2, 3, 6, 9, 12, 24, and 36 hours postdose on Day 1 and on study Days 3, 4, 7, 15, 29, 57, and 85	The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.
Percentage Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)	Baseline and Days 7, 15, 57, 155 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	Up to Day 225	An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was defined as an AE that starts on or after the first dose of investigational product and up to end of study. Clinically significant changes in clinical laboratory tests, 12-lead electrocardiograms, and vital signs were reported as AEs.
Percentage Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C)	Baseline and Days 7, 15, 57, 155 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.
Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)	Baseline and Days 7, 15, 57, 155 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.
Percentage Change From Baseline in Total Cholesterol	Baseline and Days 7, 15, 57, 155 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.
Percentage Change From Baseline in Apolipoprotein A1 (ApoA1)	Baseline and Days 7, 15, 57, 155 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.
Percentage Change From Baseline in Lipoprotein-a (Lp[a])	Baseline and Days 2, 4, 7, 15, 29, 57, 85, 113, 155, 183 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.
Percentage Change From Baseline in Apolipoprotein B (Apo B)	Baseline and Days 7, 15, 57, 155 and 225	Participants were fasted overnight (at least 10 hours) before collection of blood samples for lipids.