This is a multicenter, randomized, double-blind, factorial design Phase 2 study to evaluate the pharmacodynamics, safety and tolerability of a combination of QCZ484 and inclisiran compared to QCZ484, inclisiran, and placebo in participants with hypertension and concomitant hypercholesterolemia.

The study will last up to 12 months and has three periods:

• Eligibility will be assessed during the screening period including 2 screening visits. Some eligibility criteria will be confirmed at the Baseline/Randomization visit.
• Eligible participants will be randomized to receive a combination of QCZ484 and inclisiran, QCZ484, inclisiran or placebo once on Day 1 at the Baseline/Randomization visit.
• Afterwards, participants will enter the safety follow-up period. Eligible participants who complete the treatment period have the option to participate in an open-label extension study instead of entering the safety follow-up period.

Inclusion Criteria:

• Males or females aged 18 to 75 years.
• Diagnosis of primary hypertension.
• Treatment with either no, or up to 2 antihypertensive medications at a stable dose for at least 4 weeks preceding screening.
• Systolic blood pressure ≥140 and <165 mmHg based on the mean of 3 sitting measurements based on office blood pressure monitoring.
• Diagnosis of hypercholesterolemia including heterozygous familial hypercholesterolemia unable to reach LDL-C goals with a stable dose of statin treatment for at least 4 weeks prior to screening as per Investigator judgement, guidelines and local practice (if tolerated and not contraindicated) with or without bempedoic acid and with or without ezetimibe prescribed according to local guidance, at a stable dose for at least 4 weeks preceding Screening Visit 1.

The following parameters must be confirmed at Screening Visit 2:

• Fasting serum LDL-C ≥70 mg/dL and <190 mg/dL using Friedewald equation.
• Fasting triglyceride <400 mg/dL.

Exclusion Criteria:

• Symptomatic orthostatic hypotension.
• Treatment with certain medications and/or unable to comply with prohibited medications requirements.

Other protocol inclusion/exclusion criteria may apply

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.