Safety, Tolerability, and Pharmacokinetics of XXB750 in Healthy Participants

Novartis

Status and phase: Completed; Phase 1

Conditions: XXB750 in Healthy Participants

Treatments: Other: Placebo; Drug: XXB750

Study type: Interventional

Funder types: Industry

Identifiers

NCT06558097

CXXB750A02101

Details and patient eligibility

About

This study was a randomized, participant and investigator-blinded, placebo-controlled, single-ascending dose study, consisting of 9 sequential dose cohorts (1 mg, 3 mg, 10 mg, 30 mg, 60 mg, 120 mg, 240 mg, 450 mg and 600 mg) and a Japanese ethnic sensitivity cohort (240 mg dose)

Full description

Eligible healthy participants with normal blood pressure (SBP: 110-139 mmHg; DBP: 70-89 mmHg) were randomized into dose cohorts 1 - 240 mg. Eligible healthy participants with elevated blood pressure (SBP: 139 - 159 mmHg; DBP: 75 - 95 mmHg) were randomized into dose cohorts 450 and 600 mg. Each participant received a subcutaneous single dose of either XXB750 or placebo. In total, the duration of the study was 151 days, including the full Screening period of up to 28 days, safety, pharmacokinetics and pharmacodynamics assessments over a period of 91 days, and a 30-day safety follow up call after the end of study visit.

Sentinel dosing will be applied in this FIH study at each new dose level to ensure participant's safety and minimize the number of participants that may experience symptomatic hypotension, especially for sustained periods of time attributing to the long acting nature of XXB750 and the sustained pharmacological effects on BP at higher doses. The 10-day safety monitoring for the sentinel cohort is considered sufficient based on the predicted mean Tmax (4.5 days) in humans.

Enrollment: 77 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy male and female participants age 18 to 50 years of age included, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
• Participants must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 32 kg/m2. BMI = Body weight (kg) / [Height (m)]2
• For ethnic Japanese cohort: participants must be defined as being of first, second or third generation ethnic origin, with each set of parents qualifying as Japanese under the prior generation.

Exclusion criteria

• Any surgical or medical condition which significantly altered the distribution, metabolism, or excretion of drugs, or which jeopardized the participant's participation in the study.
• Known history or current clinically significant arrhythmias.
• Women of child-bearing potential were excluded from this study.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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77 participants in 13 patient groups, including a placebo group

XXB750 s.c 1 mg

Experimental group

Description:

Single SC dose of XXB750 1 mg

Treatment:

Drug: XXB750

XXB750 s.c 3 mg

Experimental group

Description:

Single SC dose of XXB750 3 mg

Treatment:

Drug: XXB750

XXB750 s.c 10 mg

Experimental group

Description:

Single SC dose of XXB750 10 mg

Treatment:

Drug: XXB750

XXB750 s.c 30 mg

Experimental group

Description:

Single SC dose of XXB750 30 mg

Treatment:

Drug: XXB750

XXB750 s.c 60 mg

Experimental group

Description:

Single SC dose of XXB750 60 mg

Treatment:

Drug: XXB750

XXB750 s.c 120 mg

Experimental group

Description:

Single SC dose of XXB750 120 mg

Treatment:

Drug: XXB750

XXB750 s.c 240 mg

Experimental group

Description:

Single SC dose of XXB750 240 mg

Treatment:

Drug: XXB750

Placebo

Placebo Comparator group

Description:

Placebo to XXB750

Treatment:

Other: Placebo

XXB750 s.c 240 mg Japanese cohort

Experimental group

Description:

Single SC dose of XXB750 240 mg in the Japanese cohort

Treatment:

Drug: XXB750

Placebo for Japanese cohort

Placebo Comparator group

Description:

Placebo to XXB750 in the Japanese cohort

Treatment:

Other: Placebo

XXB750 s.c 450 mg (HBP)

Experimental group

Description:

Single SC dose of XXB750 450 mg (High Blood Pressure Cohort)

Treatment:

Drug: XXB750

XXB750 s.c 600 mg (HBP)

Experimental group

Description:

Single SC dose of XXB750 600 mg (High Blood Pressure Cohort)

Treatment:

Drug: XXB750

Placebo to High Blood Pressure cohort

Placebo Comparator group

Description:

Placebo to XXB750 in High Blood Pressure cohorts

Treatment:

Other: Placebo