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Study in Adult Asthmatic Patients With Allergic Bronchopulmonary Aspergillosis

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ClinicalTrials.gov Identifier: NCT03960606
Recruitment Status : Recruiting
First Posted : May 23, 2019
Last Update Posted : October 3, 2019
Sponsor:
Information provided by (Responsible Party):
Pulmatrix Inc.

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Asthma Combination Product: PUR1900 Phase 2

Detailed Description:

This is a randomized, double-blind, multicenter, placebo controlled, multiple-arm study.

Following screening and confirmation of eligibility, subjects will be randomly assigned (1:1:1:1) into 4 arms of 16 subjects each and will receive 10 mg, 20 mg, or 35 mg of PUR1900 or placebo, administered via dry powder inhalation daily for 28 days. The doses of PUR1900 are stated in this protocol as the respective nominal doses of itraconazole.

Subject eligibility for the study will be determined within 28 days before the first dose of study drug (Day 1) and will be confirmed between 9 and 6 days before dosing and again on Day 1.

Eligible subjects will begin daily dosing with study drug (PUR1900 or placebo) on Day 1.

Subjects will return to the study site for visits on Days 2, 7, 14, and 28 and will be dosed at the study site. The remaining daily doses of study drug will be self-administered at home.

A follow-up visit will occur 7 to 10 days after the last dose of study drug.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Following screening and confirmation of eligibility, subjects will be randomly assigned (1:1:1:1) into 4 arms of 16 subjects each and will receive 10 mg, 20 mg, or 35 mg of PUR1900 or placebo, administered via dry powder inhalation daily for 28 days.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: The study will be performed in a double-blind manner. All study drug will be supplied in identical packaging and will be similar in color, smell, taste, and appearance to enable double-blind conditions. All study personnel will remain blinded until after database lock, unless the nature of their activities in the study specifically requires them to be unblinded. Any study documents, supplies, and tools will be reviewed to identify components that have the potential to unblind the study, and blinding restrictions will be applied where appropriate.
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability, & Pharmacokinetics of Itraconazole Administered as a Dry Powder for Inhalation (PUR1900) in Asthmatic Patients With ABPA
Actual Study Start Date : July 31, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: 10 mg PUR1900
Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

Experimental: 20 mg PUR1900
Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

Experimental: 35 mg PUR1900
Study drug (PUR1900) will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.

Placebo Comparator: Placebo
Placebo will be administered orally, using a Dry Powder Inhaler (DPI) specific to the study (RS01 Monodose inhaler)
Combination Product: PUR1900
PUR1900 contains itraconazole as the active ingredient, and it is formulated as a dry powder for oral inhalation.




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
  2. Incidence of intraday FEV1 declines [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
  3. Respiratory rate [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
  4. Blood pressure [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Systolic pressure over diastolic pressure

  5. Heart rate [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Beats per minute

  6. Oxygen saturation [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    As a percentage

  7. Physical examination findings [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Physician's notes

  8. Clinical laboratory test results [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    Lab reports with any out of range results flagged

  9. 12-Lead electrocardiogram findings [ Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) ]
    ECG report and tracing


Secondary Outcome Measures :
  1. Sputum concentrations of itraconazole and hydroxy-itraconazole [ Time Frame: Day 2 to Day 28 ]
  2. Sputum eosinophils [ Time Frame: (Day -9 to Day -6) to Day 28 ]
  3. To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900 [ Time Frame: Day 1 to Day 28 ]
  4. Asthma Control Questionnaire-6 (ACQ 6) [ Time Frame: Day 1 to Day 28 ]
    Scores range between 0 (totally controlled) and 6 (severely uncontrolled).

  5. Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum [ Time Frame: Day 1 to Day 28 ]
    As assessed by quantitative PCR and sputum culture

  6. Cmax (maximum observed concentration in plasma) [ Time Frame: Day 1 to Day 28 ]
  7. Tmax (time to maximum concentration in plasma) [ Time Frame: Day 1 to Day 28 ]
  8. AUC (area under the concentration-time curve) [ Time Frame: Day 1 to Day 28 ]
  9. CL/F (clearance) [ Time Frame: Day 1 to Day 28 ]
  10. Vz/F (apparent volume of distribution) [ Time Frame: Day 1 to Day 28 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  • 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 (Quanjer et al 2012) 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 of this protocol.
  • Can demonstrate the correct inhalation technique for the use of the delivery device at screening and before dosing.

Exclusion Criteria:

  • Is a female of childbearing potential who is pregnant or lactating or who plans to become pregnant during the study. 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).
  • 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.
  • 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 a positive urine test result for drugs of abuse, alcohol, or cotinine at screening
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03960606


Contacts
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Contact: Russel G. Clayton, DO 781-357-2333 rclayton@Pulmatrix.com

Locations
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United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: Allen Stevens    720-862-6613    stevensa@njhealth.org   
United States, Florida
Integrity Clinical Research Center Inc. Recruiting
Hialeah, Florida, United States, 33015
Contact: Yamilet Cantero    786-953-6263    ycanterocma@integrityresearchcenter.com   
Contact: Yaimary Diaz    786-953-6263    ydiaz@integrityresearchcenter.com   
Heuer M.D Research Inc. Recruiting
Miami Lakes, Florida, United States, 32819
Contact: Maria Arias       marias@heuermd.com   
San Marcus Research Clinic, Inc. Recruiting
Miami Lakes, Florida, United States, 33014
Contact: Yoeisi Lozada       ylozada@sanmarcusrc.com   
United States, Georgia
Infinite Clinical Trials Recruiting
Roswell, Georgia, United States, 30076
Contact: Bridgette Hall-Maynor    770-558-2873    blmaynor04@gmail.com   
United States, Illinois
University Consultants In Allergy and Immunology Recruiting
Chicago, Illinois, United States, 60612
Contact: Ben Xu    312-563-5987    ben_xu@rush.edu   
United States, Indiana
Laporte County Institute for Clinical Research Recruiting
Michigan City, Indiana, United States, 46360
Contact: Cynthia Gonzalez       cynthiagonzalez.lcicr@gmail.com   
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Contact: Mydalyn Beronilla    929-263-3262    mberonil@montefiore.org   
United States, Texas
University of Texas Medical Branch at Galveston Recruiting
Galveston, Texas, United States, 77555
Contact: Cindy Mitchell    409-772-5508    cimitche@utmb.edu   
Australia, New South Wales
John Hunter Hospital Recruiting
New Lambton, New South Wales, Australia, 2305
Contact: Douglas Dorahy    +610240420133    douglas.dorahy@newcastle.edu.au   
Australia, Queensland
Mater Private Hospital Brisbane Recruiting
Brisbane, Queensland, Australia, 4101
Contact: Rebecca Ward    07 3163 1365    Rebecca.Ward@mater.org.au   
Contact: Courtney Moloney    07 31636 2585    Courtney.Moloney@mater.org.au   
India
Yashoda Hospital Recruiting
Hyderabad, Andhra Pradesh, India, 500082
Contact: Anita Mallepaka    +918186019040    mallepaka66@gmail.com   
Shree Hospital And Critical Care Centre Recruiting
Nagpur, Maharashtra, India, 440009
Contact: Iti Ujjainkar    +917387518389    itiujjainkar@gmail.com   
Poland
Centrum Medycyny Oddechowej Mroz sp. j. Recruiting
Bialystok, Podlaskie, Poland, 15-044
Contact: Marta Augustynowicz    +48857323078    m-augustynowicz@wp.pl   
Uniwersyteckie Centrum Kliniczne - PPDS Recruiting
Gdansk, Pomorskie, Poland, 80-952
Contact: Aleksandra Wozny    +48583492568    awozny@uck.gda.pl   
PULMAG Arkadiusz Brodowski, Grzegorz Gasior S. C. Recruiting
Sosnowiec, Slaskie, Poland, 41-200
Contact: Monika Jaskolska    +48518256508    jaskolska.bk@gmail.com   
United Kingdom
Birmingham Heartlands Hospital Recruiting
Birmingham, West Midlands, United Kingdom, B9 5SS
Contact: Adel Mansur, PhD    +441214242746    adel.mansur@heartofengland.nhs.uk   
Contact: Michael Newnham    +441214242744    michael.newnham@heartofengland.nhs.uk   
Wythenshawe Hospital - PPDS Recruiting
Manchester, United Kingdom, M23 9LT
Contact: Karen Rhodes    +44 01612 915768    karen.rhodes@mft.nhs.uk   
Sponsors and Collaborators
Pulmatrix Inc.
Investigators
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Principal Investigator: William J. Calhoun, MD University of Texas Medical Branch Galveston, TX 77555
Principal Investigator: David Denning, FRCP, FRC Path, FIDSA, FMedSci Director, National Aspergillosis Centre Manchester, Wythenshawe M23 9LT, UK

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Responsible Party: Pulmatrix Inc.
ClinicalTrials.gov Identifier: NCT03960606     History of Changes
Other Study ID Numbers: 601-0014
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: October 3, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pulmatrix Inc.:
Aspergillosis
Additional relevant MeSH terms:
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Aspergillosis
Mycoses
Itraconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors