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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (inclisiran - currently marketed formulation) | Active Comparator | Inclisiran 284 mg × 1 single dose on Day 1 |
|
| Arm B (inclisiran - formulation containing PS80) | Experimental | Inclisiran 284 mg × 1 single dose on Day 1 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inclisiran formulation containing PS80 | Drug | Inclisiran 284 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Primary plasma PK parameters: Cmax | Cmax = maximum observed plasma concentration | Day 1, Day 2, Day 3 and Day 4 |
| Primary plasma PK parameters: AUClast | AUClast = AUC from time zero to the last measurable concentration sampling time | Day 1, Day 2, Day 3 and Day 4 |
| Primary plasma PK parameters: AUCinf | AUCinf = AUC from time zero to infinity | Day 1, Day 2, Day 3 and Day 4 |
| Additional PK parameters: AUC0-24hr | AUC0-24hr = AUC from time zero to 24 hours | Day 1, Day 2, Day 3 and Day 4 |
| Additional PK parameters: Tmax | Tmax = time to reach maximum plasma concentration | Day 1, Day 2, Day 3 and Day 4 |
| Additional PK parameters: T1/2 | T1/2 = elimination half-life | Day 1, Day 2, Day 3 and Day 4 |
| Additional PK parameters: CL/F | CL/F = total body clearance | Day 1, Day 2, Day 3 and Day 4 |
| Additional PK parameters: Vz/F | Vz/F = apparent volume of distribution | Day 1, Day 2, Day 3 and Day 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with AEs | Number of participants with AEs, including abnormal vital signs, ECGs, injection site reactions and safety laboratory parameters. | Up to Day 90 |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol inclusion/exclusion criteria may apply
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Novartis Pharmaceuticals | Contact | 1-888-669-6682 | novartis.email@novartis.com | |
| Novartis Pharmaceuticals | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lenexa Research Unit | Recruiting | Lenexa | Kansas | 66219 | United States | |
| Cardiovasular Renal Metabolism |
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| Currently marketed inclisiran formulation | Drug | Inclisiran 284 mg |
|
|
| Recruiting |
| San Antonio |
| Texas |
| 78232 |
| United States |
| Salt Lake City Research Unit | Recruiting | Salt Lake City | Utah | 84124 | United States |