An open-label, single-sequence cross-over drug-drug interaction study to evaluate the effect of single and multiple oral doses of PHA-022121 on the pharmacokinetics of selective CYP1A2, CYP2C19, and CYP3A4 substrates in healthy subjects

Completed

• Conditions: 10027664; Hereditary Angioedema

• Registration Number: NL-OMON49587
• Lead Sponsor: Pharvaris Netherlands BV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2021-10-15
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 14

Inclusion Criteria

1. Subject must be a healthy male or female subject, 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 or she understands the purpose
of the study including the procedures required, and is willing to participate
in the study, including that he /she 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 , intra-uterine device) 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 until 90 days after receiving the last study
drug administration.

Exclusion Criteria

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/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 4. 14, 2010 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 applies for male and female,
respectively) lowering grad 1 or greater (<=6.5 mmol ; <=109 g/L );
- 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this study is to determine the potential<br /><br>inhibitory/inducing effects of multiple doses of PHA 022121 on the single-dose<br /><br>pharmacokinetics (PK) of a cocktail, containing selective probe substrates of<br /><br>cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C19 and CYP3A4) in healthy adult<br /><br>subjects.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objectives of this study are to evaluate the safety and<br /><br>tolerability of PHA 022121 after multiple doses in the presence of a drug<br /><br>cocktail in healthy adult subjects and to assess steady-state PK of PHA-022121<br /><br>and its active metabolite M2-D in the presence of a drug cocktail in healthy<br /><br>adult subjects. </p><br>