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

Study Overview
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Brief Summary
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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]).

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

Conditions
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Elevated Serum Lipoprotein(a)

Intervention / Treatment
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* Drug: Olpasiran


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olpasiran Dose A<br>Participants will be administered Olpasiran dose A as a subcutaneous injection. | Drug: Olpasiran<br>* Subcutaneous injection<br>* Other names: AMG 890;|
| Experimental: Olpasiran Dose B<br>Participants will be administered Olpasiran dose B as a subcutaneous injection. | Drug: Olpasiran<br>* Subcutaneous injection<br>* Other names: AMG 890;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of Olpasiran |  | Day 1 to Day 85 | 
| Area Under the Concentration-time Curve (AUC) of Olpasiran |  | Day 1 to Day 85 | 
| Time to Maximum Observed Concentration (tmax) |  | Day 1 to Day 85 | 
| Half-life (t1/2) of Olpasiran |  | Day 1 to Day 85 | 
| Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Olpasiran |  | Day 1 to Day 85 | 
| Apparent Total Body Clearance (CL/F) of Olpasiran |  | Day 1 to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events |  | Day 1 to Day 225 | 
| Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests |  | Day 1 to Day 225 | 
| Number of Participants with a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) |  | Day 1 to Day 225 | 
| Number of Participants with a Clinically Significant Change from Baseline in Vital Signs |  | Day 1 to Day 225 | 
| Number of Participants with a Clinically Siginificant Change from Baseline in Lipid Levels |  | Day 1 to Day 225 | 
| Number of Participants with a Clinically Significant Change from Baseline in Serum Lipoprotein(a) (LP[a]) |  | Day 1 to Day 225 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elevated serum lipoprotein(a), Olpasiran