A randomized, phase 2 study to evaluate Safety, Tolerability and pharmacokinetics of Itraconazole as Dry Powder for Inhalation in adult Asthmatic Patients

Phase 2

Active, not recruiting

• Conditions: Other pulmonary aspergillosis,

• Registration Number: CTRI/2019/08/020764
• Lead Sponsor: Pulmatrix Inc

Brief Summary

This is a study in Adult Asthmatic Patients with Allergic Bronchopulmonary Aspergillosis.

This is randomized, double-blind, multicenter and placebo controlled, multiple-arm study. Following the screening and confirmation of eligibility, the subjects will be randomized (1:1:1:1) into 4 arms of 16 subjects each and will receive the 10mg, 20mg, or 35 mg of PUR1900 or Placebo, administered via dry powder inhalation daily for 28 days.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-08-26
• Last Update Posted: 2023-10-09

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• Can provide written informed consent before the performance of any study-specific procedures.
• Is a male or female, 18 to 75 years old (inclusive) at the time of signing the informed consent.
• Has a body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
• Has a historical diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update.
• Has a confirmed historical diagnosis of ABPA, as per the Modified International Society for Human and Animal Mycology (ISHAM) working group 2013 criteria.
• 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) (Section 13.3).
• Has a serum immunoglobulin (Ig) E ≥1000 IU/mL during screening (Visit 1 or Visit 2).
• 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.
• 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.
• 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 outlined in Section 5.8.4 of this protocol.
• Can demonstrate the correct inhalation technique for the use of the delivery device at screening and before dosing on Day 1.
• 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.

Exclusion Criteria

• 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.
• 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).
• 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).
• Is taking or has taken any herbal remedies or CYP3A4 inducers in the 28 days before first dose of study drug.
• Has used any systemic azole antifungal agent in the 6 months before first dose of study drug.
• 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.
• Had an occurrence of asthma or ABPA exacerbations within the 28 days before screening or during the 28-day period before Day 1.
• 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.
• Received any investigational medical product in a clinical research study within the previous 3 months before dosing in this study.
• Is a study site employee, an immediate family member of a study site employee, or a sponsor employee.
• Has previously received PUR1900.
• Has a history of any significant drug or alcohol abuse in the past 2 years before screening, as judged by the investigator.
• Has current tobacco or inhaled marijuana use or history of smoking tobacco or marijuana within the last 6 months before screening.
• Is a current user of e-cigarettes or has used these products within the last 6 months before screening.
• Has the absence of suitable veins for multiple venipunctures/cannulation as assessed by the investigator or designee at screening.
• 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).
• 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).
• 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.
• Has evidence or a history of clinically significant cardiovascular, renal, hepatic, or gastrointestinal disease or neurological or psychiatric disorder, as judged by the investigator.
• Has evidence or a history of endocrine, immunological, or autoimmune disease that would affect the subject’s safety or confound the assessment of study endpoints in the opinion of the investigator.
• Has a current diagnosis of any chronic airway disease other than asthma, ABPA, or bronchiectasis believed to be related to ABPA, such as chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, or Churg-Strauss syndrome.
• A subject whose predominating clinical disease burden is related to bronchiectasis (eg, a subject with 2 or more infective exacerbations of bronchiectasis in the past 12 months or a subject with chronic colonization with Pseudomonas aeruginosa) will be excluded.
• Has evidence of ventricular dysfunction, such as congestive cardiac failure, or a history of congestive cardiac failure.
• N-terminal pro B-type natriuretic peptide (NT-pro BNP) will be checked at screening only.
• A subject with a confirmed value of >400 pg/mL will not be eligible to participate.
• Has a 12-lead ECG demonstrating a mean QT interval corrected by the Fridericia formula (QTcF) >450 ms for a male subject or >470 ms for a female subject at screening.
• A repeat triplicate ECG is allowed if a mean QTcF >450 ms is recorded at Visit 1 or Visit 2.
• Has a serious adverse reaction or serious hypersensitivity to any of the formulation excipients.
• Has a history of allergies to or hypersensitivity reactions after dosing of itraconazole or other antifungal azoles.
• Had a major trauma or surgery within the last 28 days before screening.
• Has a planned or elective surgery, hospitalizations, or participation in other interventional studies any time during the study that may interfere with study logistics or safety.
• Has donated or had a loss of greater than 400 mL of blood within the 3 months before screening.
• Has the presence of hoarseness or oropharyngeal candidiasis at screening.
• Has other social, psychiatric, surgical, or medical conditions or screening laboratory abnormalities that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the investigator, would make the subject inappropriate for entry into the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The Primary outcome to evaluate safety and tolerability will be measured by:	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
• Incidence of treatment-emergent adverse	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
events	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
• Incidence of intraday FEV1 declines (from predose to postdose) of ≥10%, ≥15%, and ≥20%	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
• Vital sign measurements (respiratory rate,	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
blood pressure, heart rate, oxygen saturation	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
by pulse oximetry, oral or tympanic	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
temperature)	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
• Physical examination findings	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
• Clinical laboratory parameters	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
• 12-Lead electrocardiogram findings	Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)

Secondary Outcome Measures

Name	Time	Method
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)	Change from baseline (Day -9 to Day -6) to Day 28 in sputum eosinophil count
To evaluate the effect of PUR1900 on the	Aspergillus fumigatus burden in the sputum, as
To evaluate the effect of PUR1900 on pulmonary	function following single- and multiple-dose
To evaluate the impact of PUR1900 on respiratory symptoms, as measured by the ACQ-6	Change from baseline (Day 1) to Day 28 in ACQ-6 score

Trial Locations

Locations (4)

Post Graduate Institute of Medical Education and; 🇮🇳 Chandigarh, CHANDIGARH, India

Sawai Man Singh (SMS) Medical College and Hospital; 🇮🇳 Jaipur, RAJASTHAN, India

Shree Hospital and Critical Care Centre -Hospital; 🇮🇳 Nagpur, MAHARASHTRA, India

Yashoda Hospital; 🇮🇳 Hyderabad, TELANGANA, India

Post Graduate Institute of Medical Education and

🇮🇳Chandigarh, CHANDIGARH, India

Dr Ritesh Agarwal

Principal investigator

9478402976

agarwal.ritesh@outlook.in