HJB647 Phase 1b Study in Japanese Healthy Participants With Elevated Blood Pressure and Patients With Hypertension

Randomized, placebo-controlled, participant- and investigator-blind study consisting of two parts:

• Part 1 (SAD part): Single oral dose in healthy participants. Sentinel dosing will be applied in each cohort.
• Part 2 (MAD part): Multiple oral doses in patients with hypertension. Safety reviews will guide dose escalation and up-titration.

Inclusion criteria

• Japanese healthy participants with elevated blood pressure (Part 1) and patients with mild-to-moderate hypertension (Part 2)
• Age: 18 to 55 years (Part 1) and 18 to 60 years (Part 2)
• Body weight:

• Male: ≥ 50.0 kg
• Female: ≥ 45.0 kg
• Body Mass Index (BMI): 18.0 to 30.0 kg/m²
• Axillary body temperature: 35.0-37.5 °C
• Heart rate: 50-90 bpm
• Blood pressure criteria are as follows:

• Part 1: Healthy Participants with Elevated Blood Pressure Screening: Systolic Blood Pressure (SBP): 120 ≤ SBP ≤ 139 mmHg; Diastolic Blood Pressure (DBP): 60 ≤ DBP ≤ 94 mmHg Baseline (Day -1): SBP: 120 ≤ SBP ≤ 179 mmHg; DBP: 60 ≤ DBP ≤ 109 mmHg
• Part 2: Patients with Hypertension Screening and Baseline (Day -1): SBP: 140 ≤ SBP ≤ 179 mmHg; DBP: 60 ≤ DBP ≤ 109 mmHg

Exclusion criteria

• Significant illness, including infectious diseases that have not resolved within 30 days prior to baseline
• History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants such as:

• Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker.
• History of familial long QT syndrome or known family history of Torsades de Pointes
• Resting QT interval corrected by Fridericia's formula (QTcF) ≥ 450 msec (male) or ≥ 460 msec (female) at screening
• At screening, hypokalemia or hypomagnesemia defined as potassium or magnesium values below the LLN on repeat measurement, or laboratory abnormalities indicating hypothyroidism, as determined at the discretion of the investigator
• HbA1c ≥ 7.0% or LDL cholesterol ≥ 180 mg/dL or triglycerides ≥ 250 mg/dL
• Use of any prescription drugs or herbal supplements within 4 weeks prior to initial dosing, and/or OTC medication or dietary supplements (vitamins included) within 2 weeks prior to initial dosing
• Women of childbearing potential

Other protocol-defined inclusion/exclusion criteria may apply