Inclisiran Formulation
Conditions
Keywords
Inclisiran containing polysorbate 80, healthy male and female participants, safety, tolerability, pharmacokinetics, pharmacodynamics
Brief summary
The purpose of this study is to compare safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the currently marketed formulation of inclisiran with a new formulation containing polysorbate 80 (PS80), after a single 284 mg subcutaneous (SC) administration.
Detailed description
This is a randomized, single-dose, open-label, parallel-group, study to evaluate the PK, safety, and tolerability of inclisiran 284 mg. The study drug will be administered as a single SC injection to the abdomen administered as 2 different formulations (the marketed formulation and a test formulation containing PS80). Approximately 152 adult participants (76 per formulation) with elevated serum LDL-C, but otherwise healthy, are planned to be enrolled. The duration of the study for each participant will be approximately 118 days including the screening, up to 28 days, baseline period, and treatment period of 90 days.
Interventions
DRUGInclisiran formulation containing PS80
Inclisiran 284 mg
DRUGCurrently marketed inclisiran formulation
Inclisiran 284 mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female (non-childbearing potential) participants between 18 and 60 years of age (inclusive) with fasting serum LDL-C between 100 and 189 mg/dL (2.6 to 4.89 mmol/L) and fasting triglyceride \<400 mg/dL (\<4.52 mmol/L) that are not on statin or any other lipid lowering therapy. * Body mass index (BMI) between 18 and 35 kg/m2, inclusive, at screening with a body weight of at least 50 kg.
Exclusion criteria
* Participants with homozygous and heterozygous familial hypercholesterolemia will be excluded. * Historical or current use of any statin (i.e. study participants must be statin naive), other oral LDL-C-lowering medication or supplements that in investigators' judgment may affect serum LDL-C levels. Other protocol inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary plasma PK parameters: Cmax | Day 1, Day 2, Day 3 and Day 4 | Cmax = maximum observed plasma concentration |
| Primary plasma PK parameters: AUClast | Day 1, Day 2, Day 3 and Day 4 | AUClast = AUC from time zero to the last measurable concentration sampling time |
| Primary plasma PK parameters: AUCinf | Day 1, Day 2, Day 3 and Day 4 | AUCinf = AUC from time zero to infinity |
| Additional PK parameters: AUC0-24hr | Day 1, Day 2, Day 3 and Day 4 | AUC0-24hr = AUC from time zero to 24 hours |
| Additional PK parameters: Tmax | Day 1, Day 2, Day 3 and Day 4 | Tmax = time to reach maximum plasma concentration |
| Additional PK parameters: T1/2 | Day 1, Day 2, Day 3 and Day 4 | T1/2 = elimination half-life |
| Additional PK parameters: CL/F | Day 1, Day 2, Day 3 and Day 4 | CL/F = total body clearance |
| Additional PK parameters: Vz/F | Day 1, Day 2, Day 3 and Day 4 | Vz/F = apparent volume of distribution |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with AEs | Up to Day 90 | Number of participants with AEs, including abnormal vital signs, ECGs, injection site reactions and safety laboratory parameters. |
Countries
United States
Contacts
CONTACTNovartis Pharmaceuticals
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed