Safety, Tolerability, and Pharmacokinetics of XXB750 in Healthy Participants

NCT ID: NCT06558097

Last Updated: 2024-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-29
• Study Completion Date: 2023-03-31

Brief Summary

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)

Detailed 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.

Conditions

XXB750 in Healthy Participants

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

XXB750 s.c 1 mg

Single SC dose of XXB750 1 mg

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

XXB750 s.c 3 mg

Single SC dose of XXB750 3 mg

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

XXB750 s.c 10 mg

Single SC dose of XXB750 10 mg

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

XXB750 s.c 30 mg

Single SC dose of XXB750 30 mg

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

XXB750 s.c 60 mg

Single SC dose of XXB750 60 mg

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

XXB750 s.c 120 mg

Single SC dose of XXB750 120 mg

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

XXB750 s.c 240 mg

Single SC dose of XXB750 240 mg

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

Placebo

Placebo to XXB750

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Single SC dose of matching placebo (administered by single or multiple injections)

XXB750 s.c 240 mg Japanese cohort

Single SC dose of XXB750 240 mg in the Japanese cohort

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

Placebo for Japanese cohort

Placebo to XXB750 in the Japanese cohort

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Single SC dose of matching placebo (administered by single or multiple injections)

XXB750 s.c 450 mg (HBP)

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

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

XXB750 s.c 600 mg (HBP)

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

Group Type: EXPERIMENTAL

XXB750

Intervention Type: DRUG

Single SC dose of XXB750 (administered by single or multiple injections)

Placebo to High Blood Pressure cohort

Placebo to XXB750 in High Blood Pressure cohorts

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Single SC dose of matching placebo (administered by single or multiple injections)

Interventions

XXB750

Single SC dose of XXB750 (administered by single or multiple injections)

Intervention Type: DRUG

Placebo

Single SC dose of matching placebo (administered by single or multiple injections)

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Cypress, California, United States

Countries

United States

Other Identifiers

CXXB750A02101

Identifier Type: -

Identifier Source: org_study_id