Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a New Formulation of Inclisiran Containing Polysorbate 80 Compared to the Currently Marketed Formulation

A Randomized, Open-label, Single-dose, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Inclisiran Containing Polysorbate 80 Versus Inclisiran Alone in Participants With Elevated Low-density Lipoprotein Cholesterol

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Inclisiran Formulation
• Intervention / Treatment: Drug: Currently marketed inclisiran formulation; Drug: Inclisiran formulation containing PS80

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A (inclisiran - currently marketed formulation); Inclisiran 284 mg × 1 single dose on Day 1	Drug: Currently marketed inclisiran formulation; Inclisiran 284 mg; Other Names: KJX839
Experimental: Arm B (inclisiran - formulation containing PS80); Inclisiran 284 mg × 1 single dose on Day 1	Drug: Inclisiran formulation containing PS80; Inclisiran 284 mg; Other Names: KJX839

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): December 21, 2026
• Study Completion (Estimated): December 21, 2026

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; pharmacodynamics; Inclisiran containing polysorbate 80; healthy male and female participants
• Other Study ID Numbers: CKJX839A12107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No