Safety, Tolerability, and Pharmacokinetics of XXB750 in Healthy Participants
- Registration Number
- NCT06558097
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 77
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description XXB750 s.c 3 mg XXB750 Single SC dose of XXB750 3 mg Placebo Placebo Placebo to XXB750 XXB750 s.c 10 mg XXB750 Single SC dose of XXB750 10 mg XXB750 s.c 30 mg XXB750 Single SC dose of XXB750 30 mg XXB750 s.c 60 mg XXB750 Single SC dose of XXB750 60 mg XXB750 s.c 1 mg XXB750 Single SC dose of XXB750 1 mg XXB750 s.c 120 mg XXB750 Single SC dose of XXB750 120 mg XXB750 s.c 240 mg XXB750 Single SC dose of XXB750 240 mg XXB750 s.c 240 mg Japanese cohort XXB750 Single SC dose of XXB750 240 mg in the Japanese cohort Placebo for Japanese cohort Placebo Placebo to XXB750 in the Japanese cohort XXB750 s.c 450 mg (HBP) XXB750 Single SC dose of XXB750 450 mg (High Blood Pressure Cohort) XXB750 s.c 600 mg (HBP) XXB750 Single SC dose of XXB750 600 mg (High Blood Pressure Cohort) Placebo to High Blood Pressure cohort Placebo Placebo to XXB750 in High Blood Pressure cohorts
- Primary Outcome Measures
Name Time Method Number of participants with Adverse Events Up to 121 days To evaluate the safety and tolerability of single ascending SC doses of XXB750 in healthy participants.
Adverse events may include abnormal vital signs, safety laboratory tests, physical exam tests and ECG parameters that include clinical signs or symptoms, are considered clinically significant or require therapy.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics parameters: Tmax Up to 91 days To evaluate the pharmacokinetics: Time to maximum concentation (Tmax) of XXB750 in healthy participants following a single SC dose of XXB750.
Pharmacokinetics parameters: Vz/F Up to 91 days To evaluate the pharmacokinetics: Vd/F of XXB750 in healthy participants following a single SC dose of XXB750.
Pharmacokinetics parameters: Cmax Up to 91 days To evaluate the pharmacokinetics: Peak plasma concentration (Cmax) of XXB750 in healthy participants following a single SC dose of XXB750.
Pharmacokinetics parameters: AUClast Up to 91 days To evaluate the pharmacokinetics: Area under the plasma concentration curve (AUClast) of XXB750 in healthy participants following a single SC dose of XXB750.
Pharmacokinetics parameters: AUCinf Up to 91 days To evaluate the pharmacokinetics: Area under the curve (AUCinf) of XXB750 in healthy participants following a single SC dose of XXB750.
Pharmacokinetics parameters: T1/2 Up to 91 days To evaluate the pharmacokinetics: Half-life (T1/2) of XXB750 in healthy participants following a single SC dose of XXB750.
Pharmacokinetics parameters: CL/F Up to 91 days To evaluate the pharmacokinetics: Apparent clearance (CL/F) of XXB750 in healthy participants following a single SC dose of XXB750.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇸Cypress, California, United States