Mild Hypertension
Conditions
Keywords
Hypertension, QCZ484
Brief summary
This is a randomized, double-blind, placebo-controlled study including Part A single ascending dose (SAD) in healthy subjects and Part B single dose in subjects with mild hypertension.
Detailed description
Phase 1, multicenter, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of QCZ484. In Part A, single ascending doses of QCZ484 are tested in healthy subjects, while in Part B, single doses of QCZ484 are tested in subjects with mild hypertension. One dose of QCZ484 is administered subcutaneously. This study was started by Argo Biopharma, and global sponsorship was transferred to Novartis.
Interventions
DRUGQCZ484
doses of 50, 150, 300 or 600 mg via subcutaneous injection
DRUGPlacebo
via subcutaneous injection
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Healthy males or females aged 18 to 60 years, inclusive, at the time of informed consent. (Part A only). * Males or females aged 18 to 72 years, inclusive, at the time of informed consent (Part B only). * Body mass index (BMI) \>= 18 and \<= 32 kg/m2 and body weight \>50 kg (Part A only). * Body mass index (BMI) \>=18 and \<=35 kg/m2 and body weight \>50 kg (Part B only). * Triplicate 12-lead electrocardiogram (ECG) after \>5 minutes resting without clinically significant findings at screening and Day -1. * Mean sitting systolic blood pressure (SBP) of \>=130 and \<160 mm Hg (Part B only).
Exclusion criteria
* History of hypotension or orthostatic hypotension. * History of syncope within 1 year. * SBP \<90 mmHg or DBP \<60 mm Hg at screening (Part A only). * Clinical laboratory findings outside of range are deemed clinically significant by the investigator at screening. * Any liver function panel analyte value \> 1.2 ×upper limits of normal (ULN) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of adverse events (AEs) | Part A: up to 12 weeks post dose. Part B: up to 8 weeks post dose. | Overall number of AEs, severity, and relationship to study treatment per treatment group. |
| Number of participants with abnormalities in any laboratory parameter | Part A: up to 12 weeks post dose. Part B: up to 8 weeks post dose | Safety laboratory data (blood chemistry, hematology, coagulation, and urinalysis) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of AEs | up to 48 weeks post dose | Overall number of AEs, severity and relationship to study treatment per treatment group |
| Number of participants with abnormalities in any laboratory parameter | up to 48 weeks post dose | Safety laboratory data (blood chemistry, hematology, coagulation, and urinalysis) |
| Plasma pharmacokinetics of QCZ484 and metabolites - Cmax | Day 1; up to Day 8 | Measured by Cmax - The maximum plasma concentration of QCZ484 and of potential metabolites |
| Plasma pharmacokinetics of QCZ484 - Tmax | Day 1; up to Day 8 | Measured by Tmax - Time to Reach the Maximum Concentration After Drug Administration of QCZ484 |
| Plasma pharmacokinetics of QCZ484 and metabolites - AUC0-48 | Day 1; up to Day 8 | Measured by AUC - Area under the curve versus time curve of QCZ484 from 0 to 48 hours (AUC0-48) and of potential metabolites |
| Plasma pharmacokinetics of QCZ484 - AUC0-inf | Day 1; up to Day 8 | Measured by AUC - Area under the curve versus time curve of QCZ484 from 0 to infinity (AUC0-inf) |
| Plasma pharmacokinetics of QCZ484 - T1/2 | Day 1; up to Day 8 | Measured by T1/2 - The elimination half-life of QCZ484 |
| Urine pharmacokinetics of QCZ484 | Day 1; up to Day 2 | Measured by urine concentration of QCZ484 up to 24 hours post dose |
| Change from baseline in serum angiotensinogen (AGT) level | up to 48 weeks post dose | Measured by serum AGT level |
Countries
Australia, New Zealand
Outcome results
None listed