Safety, Tolerability, and Pharmacokinetics of XXB750 in Healthy Participants

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

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)

Study Overview

• Status: Completed
• Conditions: XXB750 in Healthy Participants
• Intervention / Treatment: Drug: XXB750; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XXB750 s.c 1 mg; Single SC dose of XXB750 1 mg	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Experimental: XXB750 s.c 3 mg; Single SC dose of XXB750 3 mg	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Experimental: XXB750 s.c 10 mg; Single SC dose of XXB750 10 mg	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Experimental: XXB750 s.c 30 mg; Single SC dose of XXB750 30 mg	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Experimental: XXB750 s.c 60 mg; Single SC dose of XXB750 60 mg	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Experimental: XXB750 s.c 120 mg; Single SC dose of XXB750 120 mg	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Experimental: XXB750 s.c 240 mg; Single SC dose of XXB750 240 mg	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Placebo Comparator: Placebo; Placebo to XXB750	Other: Placebo; Single SC dose of matching placebo (administered by single or multiple injections)
Experimental: XXB750 s.c 240 mg Japanese cohort; Single SC dose of XXB750 240 mg in the Japanese cohort	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Placebo Comparator: Placebo for Japanese cohort; Placebo to XXB750 in the Japanese cohort	Other: Placebo; Single SC dose of matching placebo (administered by single or multiple injections)
Experimental: XXB750 s.c 450 mg (HBP); Single SC dose of XXB750 450 mg (High Blood Pressure Cohort)	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Experimental: XXB750 s.c 600 mg (HBP); Single SC dose of XXB750 600 mg (High Blood Pressure Cohort)	Drug: XXB750; Single SC dose of XXB750 (administered by single or multiple injections)
Placebo Comparator: Placebo to High Blood Pressure cohort; Placebo to XXB750 in High Blood Pressure cohorts	Other: Placebo; Single SC dose of matching placebo (administered by single or multiple injections)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events	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.	Up to 121 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics parameters: Tmax	To evaluate the pharmacokinetics: Time to maximum concentation (Tmax) of XXB750 in healthy participants following a single SC dose of XXB750.	Up to 91 days
Pharmacokinetics parameters: Cmax	To evaluate the pharmacokinetics: Peak plasma concentration (Cmax) of XXB750 in healthy participants following a single SC dose of XXB750.	Up to 91 days
Pharmacokinetics parameters: AUClast	To evaluate the pharmacokinetics: Area under the plasma concentration curve (AUClast) of XXB750 in healthy participants following a single SC dose of XXB750.	Up to 91 days
Pharmacokinetics parameters: AUCinf	To evaluate the pharmacokinetics: Area under the curve (AUCinf) of XXB750 in healthy participants following a single SC dose of XXB750.	Up to 91 days
Pharmacokinetics parameters: T1/2	To evaluate the pharmacokinetics: Half-life (T1/2) of XXB750 in healthy participants following a single SC dose of XXB750.	Up to 91 days
Pharmacokinetics parameters: Vz/F	To evaluate the pharmacokinetics: Vd/F of XXB750 in healthy participants following a single SC dose of XXB750.	Up to 91 days
Pharmacokinetics parameters: CL/F	To evaluate the pharmacokinetics: Apparent clearance (CL/F) of XXB750 in healthy participants following a single SC dose of XXB750.	Up to 91 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): March 2, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 16, 2024

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: healthy participants; XXB750
• Other Study ID Numbers: CXXB750A02101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No