Clinical trial NCT06558097: Safety, Tolerability, and Pharmacokinetics of XXB750 in Healthy Participants
Official title: A First-in-human, Randomized, Sponsor Open-label, Participant and Investigator Blinded, Placebo-controlled, Single Ascending Dose Study to Explore the Safety, Tolerability and Pharmacokinetics of XXB750 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: XXB750 in Healthy Participants
Keywords: XXB750
healthy participants
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-08-16
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Number of participants with Adverse Events
timeFrame: Up to 121 days
Secondary outcomes:
measure: Pharmacokinetics parameters: Tmax
timeFrame: Up to 91 days
measure: Pharmacokinetics parameters: Cmax
timeFrame: Up to 91 days
measure: Pharmacokinetics parameters: AUClast
timeFrame: Up to 91 days
measure: Pharmacokinetics parameters: AUCinf
timeFrame: Up to 91 days
measure: Pharmacokinetics parameters: T1/2
timeFrame: Up to 91 days
measure: Pharmacokinetics parameters: Vz/F
timeFrame: Up to 91 days
measure: Pharmacokinetics parameters: CL/F
timeFrame: Up to 91 days
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Novartis Investigative Site
state: California
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: