Healthy
Conditions
Brief summary
The purpose of this first in human study is to assess safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single ascending doses of HZN-457.
Interventions
DRUGHZN-457
HZN-457 will be given in one subcutaneous administration
DRUGPlacebo
Placebo will be given in one subcutaneous administration
Sponsors
Horizon Therapeutics Ireland DAC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Screening serum uric acid (sUA) ≥ 4 mg/dL (238 µmol/L) * Screening body mass index (BMI) between 20 to 34.0 kg/m2, inclusive * Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECG findings, as deemed by the Investigator. * Male participants must refrain from donating sperm and either agree to remain abstinent from heterosexual intercourse OR agree to utilize contraception * Female participants must be non-pregnant, non-lactating postmenopausal woman of non-childbearing potential (WONCBP) with a follicle-stimulating hormone (FSH) level in the postmenopausal range (\> 40 IU/L)
Exclusion criteria
* History or presence of gout. * Use of any prescription medication within 14 days or 5 half-lives prior to dosing * Participation in another investigational clinical study (eg, drug, vaccine, invasive device) within 30 days or 5 half-lives, whichever is longer, prior to Day 1. * Current liver disease, as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels \> upper limit of normal (ULN) at Screening or Day -1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in ECG QTc values. | Baseline, Day 1 Post-Dose, Day 2, Day 4 |
| Change from Baseline in Respiratory Rate values. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Body Temperature values. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in ECG Heart Rate values. | Baseline, Day 1 Post-Dose, Day 2, Day 4 |
| Change from Baseline in ECG PR values. | Baseline, Day 1 Post-Dose, Day 2, Day 4 |
| Change from Baseline in ECG QRS values. | Baseline, Day 1 Post-Dose, Day 2, Day 4 |
| Change from Baseline in ECG QT values. | Baseline, Day 1 Post-Dose, Day 2, Day 4 |
| Incidence of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs) (injection site reactions (ISRs). | Day 1 up to Day 337 |
| Change from Baseline in Hemoglobin value. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in white blood cell counts. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in platelet counts. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Prothrombin Time. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Activated Partial Thromboplastin Time. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Aspartate Aminotransferase (AST) value. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Alanine Aminotransferase (ALT) value. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Urinalysis values. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Systolic Blood Pressure values. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Diastolic Blood Pressure values. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
| Change from Baseline in Pulse Rate values. | Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85 |
Secondary
| Measure | Time frame |
|---|---|
| Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf) | Day 1 to Day 8 |
| Elimination half-life (t1/2) | Day 1 to Day 8 |
| Fraction of the administered dose excreted into the urine (Fe) | Day 1 to Day 2 |
| Change and percent change from baseline in serum uric acid (sUA) evaluated post dosing | Day 1 to Day 337 |
| Peak plasma concentration (Cmax) | Day 1 to Day 8 |
| Time to peak plasma concentration (Tmax) | Day 1 to Day 8 |
Countries
New Zealand
Outcome results
None listed