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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)
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| XXB750 s.c 1 mg | Experimental | Single SC dose of XXB750 1 mg |
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| XXB750 s.c 3 mg | Experimental | Single SC dose of XXB750 3 mg |
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| XXB750 s.c 10 mg | Experimental | Single SC dose of XXB750 10 mg |
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| XXB750 s.c 30 mg | Experimental | Single SC dose of XXB750 30 mg |
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| XXB750 s.c 60 mg | Experimental | Single SC dose of XXB750 60 mg |
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| XXB750 s.c 120 mg | Experimental | Single SC dose of XXB750 120 mg |
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| XXB750 s.c 240 mg |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XXB750 | Drug | Single SC dose of XXB750 (administered by single or multiple injections) |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Cypress | California | 90630 | United States |
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| Experimental |
Single SC dose of XXB750 240 mg |
|
| Placebo | Placebo Comparator | Placebo to XXB750 |
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| XXB750 s.c 240 mg Japanese cohort | Experimental | Single SC dose of XXB750 240 mg in the Japanese cohort |
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| Placebo for Japanese cohort | Placebo Comparator | Placebo to XXB750 in the Japanese cohort |
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| XXB750 s.c 450 mg (HBP) | Experimental | Single SC dose of XXB750 450 mg (High Blood Pressure Cohort) |
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| XXB750 s.c 600 mg (HBP) | Experimental | Single SC dose of XXB750 600 mg (High Blood Pressure Cohort) |
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| Placebo to High Blood Pressure cohort | Placebo Comparator | Placebo to XXB750 in High Blood Pressure cohorts |
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| Placebo | Other | Single SC dose of matching placebo (administered by single or multiple injections) |
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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 |