A Phase 1 Randomized, Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HZN-457 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- HZN-457
- Conditions
- Healthy
- Sponsor
- Horizon Therapeutics Ireland DAC
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Change from Baseline in Activated Partial Thromboplastin Time.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
- •Current liver disease, as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels \> upper limit of normal (ULN) at Screening or Day -1.
Arms & Interventions
HZN-457
Intervention: HZN-457
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Change from Baseline in Activated Partial Thromboplastin Time.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Body Temperature values.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in ECG QRS values.
Time Frame: Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in Pulse Rate values.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in ECG QT values.
Time Frame: Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in Alanine Aminotransferase (ALT) value.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Systolic Blood Pressure values.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Diastolic Blood Pressure values.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Incidence of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs) (injection site reactions (ISRs).
Time Frame: Day 1 up to Day 337
Change from Baseline in Hemoglobin value.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in white blood cell counts.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in platelet counts.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Urinalysis values.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in ECG Heart Rate values.
Time Frame: Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in ECG QTc values.
Time Frame: Baseline, Day 1 Post-Dose, Day 2, Day 4
Change from Baseline in Prothrombin Time.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Aspartate Aminotransferase (AST) value.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in Respiratory Rate values.
Time Frame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 43, Day 85
Change from Baseline in ECG PR values.
Time Frame: Baseline, Day 1 Post-Dose, Day 2, Day 4
Secondary Outcomes
- Time to peak plasma concentration (Tmax)(Day 1 to Day 8)
- Peak plasma concentration (Cmax)(Day 1 to Day 8)
- 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)