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

An Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Olpasiran in Chinese Subjects With Elevated Serum Lipoprotein(a)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04987320

Enrollment

Registered

2021-08-03

Start date

2021-07-28

Completion date

2022-03-18

Last updated

2025-02-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Elevated Serum Lipoprotein(a)

Keywords

Elevated serum lipoprotein(a), Olpasiran

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\[a\]).

Interventions

DRUGOlpasiran

Subcutaneous injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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.
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 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.
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.
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 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.
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 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 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.
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 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.
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 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.

Countries

Hong Kong

Participant flow

Participants by arm

Arm	Count
Olpasiran Low Dose Participants were administered a single dose of olpasiran low dose as a subcutaneous injection on Day 1.	12
Olpasiran High Dose Participants were administered a single dose of olpasiran high dose as a subcutaneous injection on Day 1.	12
Total	24

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Olpasiran Low Dose	Olpasiran High Dose	Total
Age, Continuous	41.3 years STANDARD_DEVIATION 11.23	49.4 years STANDARD_DEVIATION 9.23	45.3 years STANDARD_DEVIATION 10.88
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants	12 Participants	24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	12 Participants	12 Participants	24 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants
Sex: Female, Male Female	2 Participants	5 Participants	7 Participants
Sex: Female, Male Male	10 Participants	7 Participants	17 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 12
other Total, other adverse events	11 / 12	9 / 12
serious Total, serious adverse events	1 / 12	1 / 12

Outcome results

Primary

Maximum Observed Concentration (Cmax) of Olpasiran

The serum pharmacokinetic (PK) parameters of olpasiran were calculated using standard noncompartmental methods.

Time frame: 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

Population: PK Analysis Set: included all randomized participants who received olpasiran and had evaluable PK data.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Olpasiran Low Dose	Maximum Observed Concentration (Cmax) of Olpasiran	144 ng/mL	Geometric Coefficient of Variation 55.5
Olpasiran High Dose	Maximum Observed Concentration (Cmax) of Olpasiran	549 ng/mL	Geometric Coefficient of Variation 71.5

Secondary

Apparent Terminal Elimination Half-life (T1/2) of Olpasiran

The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.

Time frame: 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

Population: PK Analysis Set: included all randomized participants who received olpasiran and had evaluable PK data.

Arm	Measure	Value (MEAN)	Dispersion
Olpasiran Low Dose	Apparent Terminal Elimination Half-life (T1/2) of Olpasiran	6.05 hours	Standard Deviation 1.59
Olpasiran High Dose	Apparent Terminal Elimination Half-life (T1/2) of Olpasiran	6.69 hours	Standard Deviation 1.58

Secondary

Apparent Total Body Clearance (CL/F) of Olpasiran

The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.

Time frame: 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

Population: PK Analysis Set: included all randomized participants who received olpasiran and had evaluable PK data.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Olpasiran Low Dose	Apparent Total Body Clearance (CL/F) of Olpasiran	28.2 L/h	Geometric Coefficient of Variation 24
Olpasiran High Dose	Apparent Total Body Clearance (CL/F) of Olpasiran	18.8 L/h	Geometric Coefficient of Variation 41.2

Secondary

Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Olpasiran

The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.

Time frame: 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

Population: PK Analysis Set: included all randomized participants who received olpasiran and had evaluable PK data.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Olpasiran Low Dose	Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Olpasiran	238 liters	Geometric Coefficient of Variation 43.5
Olpasiran High Dose	Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Olpasiran	176 liters	Geometric Coefficient of Variation 60.2

Secondary

Area Under the Serum Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Olpasiran

The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.

Time frame: 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

Population: PK Analysis Set: included all randomized participants who received olpasiran and had evaluable PK data.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Olpasiran Low Dose	Area Under the Serum Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Olpasiran	2660 h*ng/mL	Geometric Coefficient of Variation 24
Olpasiran High Dose	Area Under the Serum Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Olpasiran	12000 h*ng/mL	Geometric Coefficient of Variation 41.2

Secondary

Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Olpasiran

The serum PK parameters of olpasiran were calculated using standard noncompartmental methods.

Time frame: 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

Population: PK Analysis Set: included all randomized participants who received olpasiran and had evaluable PK data.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Olpasiran Low Dose	Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Olpasiran	2660 h*ng/mL	Geometric Coefficient of Variation 24.2
Olpasiran High Dose	Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Olpasiran	12000 h*ng/mL	Geometric Coefficient of Variation 41.3

Secondary

Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)

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.

Time frame: Up to Day 225

Population: Safety Analysis Set: included all randomized participants who received olpasiran.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Olpasiran Low Dose	Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	12 Participants
Olpasiran High Dose	Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)	10 Participants

Secondary