CTRI/2019/08/020764 [Registered on: 19/08/2019] Trial Registered Prospectively
Last Modified On:
10/09/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A randomized, phase 2 study to evaluate Safety, Tolerability and pharmacokinetics of Itraconazole as Dry Powder for Inhalation in adult Asthmatic Patients
Scientific Title of Study
A Randomized, Double-Blind, Multicenter, Placebo-Controlled, Phase 2
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of
Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) in
Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
2018-002949-11
EudraCT
601-0014 dated 06Feb2019
Protocol Number
NCT03960606
ClinicalTrials.gov
version 2.0 Amendment 1 dated 06/02/2019
DCGI
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Rashmi Chitgupi
Designation
Associate Director - Clinical Management
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
PPD Pharmaceutical Development India Private Limited, 101, A
Wing, Fulcrum, Hiranandani Business Park Sahar Road, Andheri
East,Mumbai 101, A
Wing, Fulcrum, Hiranandani Business Park Sahar Road, Andheri
East,Mumbai Mumbai MAHARASHTRA 400099 India
Phone
912266022900
Fax
912266022999
Email
Rashmi.Chitgupi@ppdi.com
Details of Contact Person Public Query
Name
Rashmi Chitgupi
Designation
Associate Director - Clinical Management
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
PPD Pharmaceutical Development India Private Limited. 101, A
Wing, Fulcrum, Hiranandani Business Park Sahar Road, Andheri
East, Mumbai 101, A
Wing, Fulcrum, Hiranandani Business Park Sahar Road, Andheri
East, Mumbai Mumbai MAHARASHTRA 400099 India
Phone
912266022900
Fax
912266022999
Email
Rashmi.Chitgupi@ppdi.com
Source of Monetary or Material Support
Pulmatrix, Inc.
99 Hayden Avenue, Suite 390
Lexington, MA 02421
Primary Sponsor
Name
Pulmatrix Inc
Address
99 Hayden Avenue, Suite 390
Lexington, MA 02421
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
PPD Pharmaceuticals Development India Private Limited
101, A Wing, Fulcrum, Hiranandani Business
Park, Sahar Road, Andheri East, Mumbai 400099,
Maharashtra, India
Countries of Recruitment
Australia India Poland United Kingdom United States of America
Sites of Study
No of Sites = 4
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Ritesh Agarwal
Post Graduate Institute of Medical Education and
New Outpatient Block, 3rd Floor, Sector 12 Chandigarh CHANDIGARH
9478402976
agarwal.ritesh@outlook.in
Dr Narendra Khippal
Sawai Man Singh (SMS) Medical College and Hospital
Department of Clinical Research, Ground Floor, Institute of Respiratory Diseases,
B-2 Subhash Nagar Shopping Center,
Shastri Nagar
Jaipur RAJASTHAN
9829017619
drnkhippal@rediffmail.com
Dr Akash Balki
Shree Hospital and Critical Care Centre -Hospital
3rd Floor, Clinical Research Room, Shree Hospital Unit, 799, Om Nagar, Opp Tajshree Building,Sakkardara Square
Nagpur MAHARASHTRA
9890812215
akash_balki@yahoo.com
Dr Venkata Nagarjuna Maturu
Yashoda Hospital
Department of Clinical Research, Room No 310, B- Block, Rajbhavan Road, Somajiguda
Hyderabad TELANGANA
Placebo will be administered orally using Dry Powder Inhaler, once daily for 28 days
Intervention
PUR1900
10mg, 20mg or 35mg of PUR1900 using Dry Powder Inhaler, once daily for 28 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
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) (Section 13.3).
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
outlined in Section 5.8.4 of this protocol.
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.
ExclusionCriteria
Details
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 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 disorder, as judged by the investigator.
20. 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.
21. 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.
22. 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.
23. 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.
24. Has a serious adverse reaction or serious hypersensitivity to any of the formulation
excipients.
25. Has a history of allergies to or hypersensitivity reactions after dosing of itraconazole or other antifungal azoles.
26. Had a major trauma or surgery within the last 28 days before screening.
27. 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.
28. Has donated or had a loss of greater than 400 mL of blood within the 3 months before
screening.
29. Has the presence of hoarseness or oropharyngeal candidiasis at screening.
30. 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
The Primary outcome to evaluate safety and tolerability will be measured by:
• 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
Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose)
Secondary Outcome
Outcome
TimePoints
To characterize the pharmacokinetics of multiple
doses of inhaled PUR1900 in plasma and sputum
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
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
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
To evaluate the effect of PUR1900 on pulmonary
function following single- and multiple-dose
administration of PUR1900
Change from baseline (Day 1) to Day 28 in FEV1
Change from baseline (Day 1) to Day 28 in FVC, PEF, and FEV1/FVC
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
To evaluate the effect of PUR1900 on the
Aspergillus fumigatus burden in the sputum, as
assessed by quantitative PCR and sputum culture
Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum as assessed by quantitative PCR and sputum culture
Target Sample Size
Total Sample Size="64" Sample Size from India="12" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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.