Asthma with Allergic Bronchopulmonary Aspergillosis MedDRA version: 20.1 Level: PT Classification code 10006474 Term: Bronchopulmonary aspergillosis allergic System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Code: PUR1900
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: ITRACONAZOLE
CAS Number: 84625-61-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Pulmatrix, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each subject must meet all the following criteria to be enrolled in this study: 1.Can provide written informed consent before the performance of any study-specific procedures. 2.Is a male or female, 18 to 75 years old (inclusive) at the time of signing the informed consent. 3.Has a body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening. 4.Has a historical diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update. 5.Has a confirmed historical diagnosis of ABPA, as per the Modified International Society for Human and Animal Mycology (ISHAM) working group 2013 criteria. 6.Is currently considered to be in one of the following stages of ABPA: Stage 2 (Response), Stage 4 (Remission), Stage 5a (Treatment-dependent ABPA), or Stage 5b (Glucocorticoid-dependent asthma). 7.Has a serum immunoglobulin (Ig) E =1000 IU/mL during screening (Visit 1 or Visit 2). 8.Can perform a valid, reproducible spirometry test with demonstration of a prebronchodilator FEV1 =50% of predicted normal for age, sex, race, and height at a screening visit. 9.Has a documented stable asthma medication regimen during screening (Day 28 to Day 1), including SABA, LABA, and LTRA use and inhaled and/or oral GCS. 10.Subjects who are sexually active, male subjects able to father a child, and female subjects of childbearing potential must agree to follow the contraception requirements. 11.Can demonstrate the correct inhalation technique for the use of the delivery device at screening and before dosing on Day 1. 12.Is willing and able to comply with all study procedures and assessments, including scheduled visits, drug dosing plan, study procedures, laboratory tests, and study restrictions. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: A subject who meets any of the following criteria will be excluded from the study: 1.Has used any anti-IgE (eg, Xolair® [omalizumab]) or anti-interleukin-5 (IL-5) biologics (eg, Cinqair® [reslizumab], Nucala® [mepolizumab], or Fasenra® [benralizumab]) in the 6 months before first dose of study drug. 2.Is a female of childbearing potential who is pregnant or lactating or who plans to become pregnant during the study (all female subjects must have a negative pregnancy test at screening and predose on Day 1). A woman is considered to be of childbearing potential unless she is either permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or postmenopausal (had no menses for 12 months without an alternative medical cause). 3.Is taking or has taken any prescribed or over-the-counter (OTC) drug that is a CYP3A4 inhibitor or substrate in the 14 days (or 5 half-lives, whichever is longer) before first dose of study drug and for the duration of the study (exclusion also applies to the whole fruit or juices of grapefruit and Seville or pomelo oranges). 4.Is taking or has taken any herbal remedies or CYP3A4 inducers in the 28 days before first dose of study drug. 5.Has used any systemic azole antifungal agent in the 6 months before first dose of study drug. 6.Has a history of life-threatening asthma within the last 5 years, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures. 7.Had an occurrence of asthma or ABPA exacerbations (as defined in Section 13.5) within the 28 days before screening or during the 28-day period before Day 1. 8.Had an occurrence of clinically significant bacterial, viral, or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals, or antifungals within the 28 days before screening. Topical treatments, other than antifungals, are allowed. 9.Received any investigational medical product in a clinical research study within the previous 3 months before dosing in this study. 10.Is a study site employee, an immediate family member of a study site employee, or a sponsor employee. 11.Has previously received PUR1900. 12.Has a history of any significant drug or alcohol abuse in the past 2 years before screening, as judged by the investigator. 13.Has current tobacco or inhaled marijuana use or history of smoking tobacco or marijuana within the last 6 months before screening. 14.Is a current user of e-cigarettes or has used these products within the last 6 months before screening. 15.Has the absence of suitable veins for multiple venipunctures/cannulation as assessed by the investigator or designee at screening. 16.Has evidence or history of clinically significant abnormal serum chemistry, hematology, or urinalysis at screening, as judged by the investigator (particularly elevation of liver enzymes or bilirubin). 17.Has a positive urine test result for drugs of abuse, alcohol, or cotinine at screening (unless, in the opinion of the investigator, this can be explained by the subject’s current medications). 18.Has a positive human immunodeficiency virus (HIV; type A and type B) antibody result: a subject who is HIV antibody positive is not excluded if a subsequent CD4 count is =200 cells/µL. 19.Has evidence or a history of clinically significant cardiovascular, renal, hepatic, or gastrointestinal disease or neurological or psychiatric di
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of multiple dose administration of PUR1900 given to adult asthmatic subjects with ABPA.;Secondary Objective: To characterize the pharmacokinetics of multiple doses of inhaled PUR1900 in plasma and sputum. To evaluate the effect of PUR1900 on biomarkers of inflammation (sputum eosinophils and serum IgE). To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900. To evaluate the impact of PUR1900 on respiratory symptoms, as measured by the ACQ 6. To evaluate the effect of PUR1900 on the Aspergillus fumigatus burden in the sputum, as assessed by quantitative PCR and sputum culture.;Timepoint(s) of evaluation of this end point: Daily for 28 days;Primary end point(s): •Incidence of treatment-emergent adverse events •Incidence of intraday FEV1 declines (from predose to postdose) of =10%, =15%, and =20% •Vital sign measurements (respiratory rate, blood pressure, heart rate, oxygen saturation by pulse oximetry, oral or tympanic temperature) •Physical examination findings •Clinical laboratory parameters •12-Lead electrocardiogram findings | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Daily for 28 days;Secondary end point(s): •Pharmacokinetic parameters of itraconazole and hydroxy-itraconazole in plasma, including, but not limited to, Cmax, Tmax, AUC, CL/F, and Vz/F •Sputum concentrations of itraconazole and hydroxy-itraconazole on Day 2, on Day 14, and at follow-up •Change from baseline (Day -9 to Day -6) to Day 28 in sputum eosinophil count •Change from baseline (Day -9 to Day -6) to Day 28 in percentage of sputum eosinophils •Change from baseline (Day 1) to Day 28 in IgE plasma concentration •Change from baseline (Day 1) to Day 28 in FEV1 •Change from baseline (Day 1) to Day 28 in FVC, PEF, and FEV1/FVC •Change from baseline (Day 1) to Day 28 in ACQ-6 score •Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum as assessed by quantitative PCR and sputum culture | — |
Countries
Australia, India, Poland, United Kingdom, United States
Contacts
Public ContactClinical Operations
Pulmatrix, Inc
Outcome results
None listed