A two parts, open-label, single-dose mass balance and absolute bioavailability study with an oral regular dose of PHA-022121 and an oral (part 1) and intravenous (part 2) microtracer dose of 14C-PHA-022121 in healthy male subjects
- Conditions
- Hereditary Angioedema10027664
- Registration Number
- NL-OMON51216
- Lead Sponsor
- Pharvaris Netherlands BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1. Subject must be a healthy male, between 18 to 65 years of age, extremes
included, at screening.
2. Subject must have a body mass index (BMI; weight in kg divided by the square
of height in meters) between 18.0 and 30.0 kg/m2, extremes included, and a body
weight not less than 50.0 kg, inclusive, at screening.
3. Subject must sign an ICF indicating that he understands the purpose of the
study including the procedures required, and is willing to participate in the
study, including that he agrees to provide DNA samples for research, before
starting of any screening activities.
4. During the study and for a minimum of 1 spermatogenesis cycle (defined as up
to and including 90 days after receiving the study drug), a male subject may be
enrolled if he is willing and able to adhere to the contraceptive requirement
as specified in 4.5 item 12 in the protocol.
5. Subject must be willing and able to adhere to the prohibitions and
restrictions.
Further criteria apply.
1. Subject has a history of current clinically significant medical illness
including (but not limited to) cardiac arrhythmias or other cardiac disease,
hematologic disease, lipid abnormalities, significant pulmonary disease,
including bronchospastic respiratory disease, diabetes mellitus, hepatic or
renal insufficiency (estimated creatinine clearance < 61 mL/min/1.73m2 at
screening, calculated by MDRD formula), thyroid disease, neurologic or
psychiatric disease, infection, or any other illness, that in the
investigator*s and/or sponsor*s medical monitor opinion should exclude the
subject or that could interfere with the interpretation of the study results.
2. Subject has one of the following laboratory abnormalities at screening as
defined by the National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (CTCAE) version 5.0, 27 November, 2017 and in accordance with
the normal ranges of the clinical laboratory if no gradings are available.
- Serum creatinine elevation grade 1 or greater (>1.1 x upper limit of normal
range [ULN])
- Hemoglobin below LLN (reference of site);
- Platelet count below LLN;
- Absolute neutrophil count lowering grade 1 or greater (<=1,5 109/L );
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=ULN;
- Total bilirubin>=ULN;
- Any other toxicity grade 2 or above, except for grade 2 elevations for
triglycerides, low density lipoprotein (LDL) cholesterol and/or total
cholesterol.
3. Clinically significant abnormal values for hematology, clinical chemistry or
urinalysis at screening or at admission to the clinical site on Day -1 as
deemed appropriate by the investigator.
4. Subject, at screening, has a positive test of human immunodeficiency virus
(HIV) 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C
antibodies.
5. Subject has a history of heart arrhythmias , tachycardia at rest or history
of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family
history of long QT syndrome).
Further criteria apply.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Part 1:<br /><br>The primary objective of this study is to characterize the absorption,<br /><br>metabolism and excretion of orally administered radiolabeled PHA-022121 in<br /><br>healthy male subjects.<br /><br><br /><br>Part 2:<br /><br>The primary objective is to determine the absolute bioavailability of orally<br /><br>administered PHA-022121 in healthy male subjects.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Part 1:<br /><br>The secondary objective of this study is to evaluate safety and tolerability of<br /><br>a single oral dose of radiolabeled PHA-022121 administered in healthy male<br /><br>subjects.<br /><br><br /><br>Part 2:<br /><br>The secondary objectives are<br /><br>- To evaluate the safety and tolerability of simultaneously administered<br /><br>unlabelled (orally) and radiolabeled (intravenously) PHA-022121 in healthy<br /><br>male subjects.<br /><br>- To determine the mass balance after an intravenously (IV) dose of a<br /><br>microdose/microtracer dose of PHA-022121.<br /><br><br /><br>Optional after the results of study PHA022121-C003 and the mass balance data<br /><br>after IV dosing of a microdose/microtracer dose of PHA-022121 are available:<br /><br><br /><br>- To characterize the metabolism of intravenously administered radiolabeled<br /><br>PHA-022121 in healthy male subjects.</p><br>