Study to evaluate the pharmacokinetics and pharmacodynamics of inclisiran treatment given as single subcutaneous injection in Chinese participants with elevated low-density lipoprotein cholesterol (LDL-C) despite treatment with LDL-C lowering therapies
The purpose of the study is to characterize pharmacokinetics, pharmacodynamics, safety and tolerability of inclisiran in Chinese participants with elevated serum LDL-C to support inclisiran registration in China.Inclisiran is a long acting RNA therapeutic agent that inhibits the synthesis of PCSK9, leading to reduced circulating LDL-C levels. Three pivotal Phase III studies have been conducted primarily in non-Asian participants to support New Drug Application/Marketing Authorization Application approval of inclisiran globally. This study design is based on the hypothesis that the global inclisiran clinical data primarily obtained in Caucasian participants could be appropriately extrapolated to Chinese participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
100 mg inclisiran sodium (equivalent to 94.5 mg inclisiran) in 0.5 mL solution. Subcutaneous administration at Day 1
Inclisiran sodium 0mg (equivalent to inclisiran 0 mg) in 1.5 mL solution. Subcutaneous administration at Day 1
300 mg inclisiran sodium (equivalent to 284 mg inclisiran) in 1.5 mL solution. Subcutaneous administration at Day 1
Novartis Investigative Site
Changsha, Hunan, China
Novartis Investigative Site
Chengdu, Sichuan, China
Novartis Investigative Site
Beijing, China
PK parameters (Cmax) maximum peak observed plasma inclisiran concentration in treated participants
Pharmacokinetics parameters of inclisiran
Time frame: 0-48 hours post-dose
PK parameters (Tmax) time to reach maximum peak plasma inclisiran concentration in treated participants
Pharmacokinetics parameters of inclisiran
Time frame: 0-48 hours post-dose
PK parameters (T1/2) the elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve in inclisiran treated participants
Pharmacokinetics parameters of inclisiran
Time frame: 0-48 hours post-dose
PK parameters (AUC) area under the plasma concentration-time curve in inclisiran treated participants
Pharmacokinetics parameters of inclisiran
Time frame: 0-48 hours post-dose
Percentage change in Proprotein convertase subtilisin kexin 9 (PCSK9) from baseline overtime
Pharmacodynamics effects of inclisiran
Time frame: Baseline to Days 5, 8, 15, 30, 60 and 90
Percentage change in Low density lipoprotein cholesterol (LDL-C) from baseline overtime
Pharmacodynamics effects of inclisiran
Time frame: Baseline to Days 5, 8, 15, 30, 60 and 90
Percent change from baseline to Days 30, 60 and 90 in PD parameter Proprotein convertase subtilisin kexin 9 (PCSK9)
Pharmacodynamics differences between inclisiran and placebo
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Time frame: Baseline to Days 30, 60 and 90
Percent change from baseline to Days 30, 60 and 90 in PD parameter Low density lipoprotein cholesterol (LDL-C)
Pharmacodynamics differences between inclisiran and placebo
Time frame: Baseline to Days 30, 60 and 90
Rate of formation of anti-drug antibodies to Inclisiran
Immunogenicity of inclisiran
Time frame: Baseline, Days 30 and 90