An open-label, single-sequence crossover drug-drug interaction study to evaluate the effect of multiple oral doses of itraconazole on the pharmacokinetics of PHA-022121 in healthy subjects
- Conditions
- Hereditary Angioedema10027664
- Registration Number
- NL-OMON49496
- Lead Sponsor
- Pharvaris BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 14
1. Subject must be a healthy male or female subject, between 18 to 60 years of
age, extremes included, at screening.
2. Subject must have a body mass index 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
approximately 90 days) after receiving the last dose of study drug, a male
subject: - who is sexually active with a woman of child-bearing potential and
has not had a vasectomy, must agree to use a barrier method of contraception
(eg, condom or partner with occlusive cap [diaphragm or cervical/vault caps]).
In addition, their female partner should also use a highly effective method of
birth control (eg, hormonal contraception) for at least the same duration. -
Who is sexually active with a woman who is pregnant must use a condom. - Must
agree not to donate sperm.
5. A female subject must be of non-childbearing potential at screening, defined
as: - Postmenopausal. A postmenopausal state is defined as no menses for 12
months without an alternative medical cause. A high follicle stimulating
hormone (FSH) level at screening (>33.4 IU/L ) in the postmenopausal range may
be used to confirm a postmenopausal state in woman not using hormonal
contraception or hormonal replacement therapy, however in the absence of 12
months of amenorrhea, a single FSH measurement is insufficient. - Permanently
sterile. Permanent sterilization methods include hysterectomy, bilateral
salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral
oophorectomy.
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 <90 mL/min 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 World Health Organization (WHO) Toxicity Grade Scale 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 lowering grade 1 or greater (<=6.5 mmol ;
<=109 g/L); - Platelet count below LLN; - Absolute neutrophil count lowering
grade 1 or greater (<=1,5 109/ ); - 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 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 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).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary PK parameters are Cmax, AUClast, and AUC* of the PHA-022121. All<br /><br>parameters will be analyzed on a logarithmic scale. AUC* will be rejected as<br /><br>primary parameter for a treatment if more than half of the subjects do not have<br /><br>a reliable value for that treatment.</p><br>
- Secondary Outcome Measures
Name Time Method <p>NA</p><br>