Hereditary Angioedema (HAE)
Conditions
Sponsors
Pharvaris B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Healthy male and female subjects of non-childbearing potential Between 18 and 65 years of age, inclusive. Body Mass Index (BMI) between 18.0 and 30 kg/m2 (inclusive). Healthy on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead ECG performed at screening. If any of the results are abnormal, the subject may be included only if the investigator judges that the abnormalities or deviations from normal are not clinically significant. This determination must be recorded in the subject's source documents and initialled by the investigator. A resting heart/pulse rate (supine position for 5 minutes) between 40 and 100 beats per minute (bpm). If heart/pulse rate is out of range, up to 2 repeated assessments are permitted. A resting blood pressure (supine position for 5 minutes) between 90 and 140 mmHg systolic, inclusive, and between 40 to 90 mmHg diastolic. If blood pressure requirements are out of range, up to 2 repeated assessments are permitted.
Exclusion criteria
Exclusion criteria: Clinically relevant allergy (except for untreated, asymptomatic, seasonal allergies at time of dosing) or drug hypersensitivity. Known hypersensitivity to the drug substance, or any inactive ingredient(s) of the investigational product (refer to investigator's Brochure). History of any medical condition or prior surgery of the GI-tract that could alter the absorption of orally administered drugs (does not apply to history of appendectomy). History or current evidence of any form of angioedema. History or current evidence of any form of bronchial asthma. History of postural disorders, i.e. labile blood pressure or symptomatic orthostatic hypotension, faintings, or blackouts) and/or treatment requiring hypotension
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint, safety: - All standard safety assessments including physical examination, vital signs, adverse events, neurological assessment, hematology, chemistry, urinalysis and ECG Primary endpoint, pharmacokinetics: - After the first and second dose on Day 1: Plasma PK parameters, Cmax, 1, Cmax, 2, tmax, 1, tmax, 2, AUC0-12h, AUC0-24h, AUClast, AUCinf, t1/2, CL/F and Vz/F of PHA-022121. The following urinary PK parameters of PHA-021221 will be derived (x-y represent the different time intervals): Ae x-y, Ae total, Durine,x-y, Durine,total and CLR. After the morning dose on Day 10: Plasma PK parameters Cmax, tmax, AUC0-12h, AUC0-24h, AUClast, t1/2, CL/F and Vss/F of PHA-022121. Urinary PK parameters of PHA-021221 will be derived as on Day 1. Cmin (pre-dose) every morning. | — |
Secondary
| Measure | Time frame |
|---|---|
| - After the first and second dose on Day 1: Plasma PK parameters for the major metabolite M2-D: Cmax, 1 , Cmax, 2, tmax, 1, tmax, 2, AUC0-12h, AUC0-24h, AUClast, AUCinf, and t1/2,. The following urinary PK parameters of M2-D will be derived (x-y represent the different time intervals): Ae x-y, Ae total, Durine,x-y, Durine,total and CLR. - After the morning dose on Day 10: Plasma PK parameters for the major metabolite M2-D: Cmax, tmax, AUC0-12h, AUC0-24h, AUClast, and t1/2,. Urinary PK parameters of M2-D will be derived as on Day 1. - Cmin (pre-dose) every morning. - 4-βHC plasma levels and urinary 6-βHC / cortisol ratio as biomarkers for CYP3A4 activity. - QT, and the corrected QT interval by Fridericia*s formula (QTcF) | — |
Countries
Netherlands
Outcome results
None listed