AsthmaPhase 1NCT03479411
Safety, Tolerability and Pharmacokinetics of PUR1900 (Itraconazole Powder) in Healthy Volunteers and Adults With Asthma
A Phase 1 study testing Itraconazole Powder and Itraconazole 200 mg in people with Asthma, run by Pulmatrix Inc. at 2 sites in United Kingdom.
Trial summary
Phase 1, 3-part study to assess safety, tolerability and PK of single and multiple doses of itraconazole administered as a dry powder for inhalation (PUR1900) in healthy subjects (parts 1 and 2) and a 2-period crossover study of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and an… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- Itraconazole Powder and Itraconazole 200 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 9 Feb 2018to 28 Jun 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Part 1 (SAD) and Part 2 (MAD):
- Healthy males or non-pregnant, non-lactating healthy females.
- Age 18 to 60 years
- Screening forced expiratory volume in 1 sec (FEV1) ≥80% of the predicted value
- Screening FEV1/forced vital capacity (FVC) >0.70.
- Able to demonstrate the correct inhalation technique for use of delivery device during the study.
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- Part 3 (Asthmatic Subjects):
- Males or non-pregnant, non-lactating females with a physician-confirmed diagnosis of asthma for at least 3 months. Asthma must be assessed by investigator as being stable for at least 4 weeks prior to screening.
- Age 18 to 60 years
- Subject is being treated with either inhaled corticosteroids (ICS) or inhaled corticosteroids plus long-acting beta-agonists (ICS/LABA). Only GINA STEP 2 and 3 patients will be enrolled.
- Pre-bronchodilator, clinic measured, FEV1 ≥70% of predicted normal at screening
- Able to perform the required spirometric testing.
- Able to produce a sputum sample of a quality required for drug concentration assessments (a single repeat is permitted).
Who cannot join
- Subjects who have received any IMP in a clinical research study within the previous 3 months prior to dosing on this study
- Subjects who have previously received IMP in this study. Subjects who have participated in Part 1 are not permitted to participate in Part 2 or Part 3.
- History of any drug or alcohol abuse in the past 2 years prior to screening.
- Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
- Females of childbearing potential who are pregnant or lactating, or who plan to become pregnant during the study (all female subjects must have a negative pregnancy test at screening). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or is postmenopausal (had no menses for 12 months without an alternative medical cause (will be re-assessed at admission/pre-dose).
- Positive drugs of abuse test result at screening or admission
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- Subjects with congestive heart failure or a history of congestive heart failure
- History of severe cough or bronchospasm upon inhalation of any dry powder inhalation product
- Subjects who are taking or have taken any herbal remedies or CYP3A4 inducers in the 28 days prior to the first IMP administration
- Upper respiratory tract infection (excluding otitis media), fever, acute or chronic cough within 14 days of the first IMP administration, or lower respiratory tract infection within the last 3 months prior to IMP administration
- Recent (last 4 weeks prior to IMP administration) clinically significant bacterial, viral or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals or antifungals; topical treatments, other than antifungals, are allowed.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Medicines Evaluation Unit
Manchester
Quotient Sciences
Nottingham
About this study
Official title: Phase 1, 3-Part, Open-Label Study to Assess Safety, Tolerability and PK of Single and Multiple Doses of PUR1900 in Healthy Subjects and Crossover Study of Single Doses of PUR1900 and Sporanox in Adult Subjects With Mild to Moderate Asthma
Phase 1, 3-part study to assess safety, tolerability and PK of single and multiple doses of itraconazole administered as a dry powder for inhalation (PUR1900) in healthy subjects (parts 1 and 2) and a 2-period crossover study of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and an oral solution (Sporanox) in adults with mild to moderate, stable asthma (part 3)
Read the detailed description
Phase 1, multi-center, 3-part, open-label study in healthy adults (Parts 1 and 2) and adults with mild to moderate, stable asthma (Part 3).
Safety, tolerability and PK will be assessed following either single ascending (SAD) or multiple ascending (MAD) dosing of itraconazole administered as a dry powder for inhalation (PUR1900; Part 1 and Part 2, respectively). Part 1 will comprise 3 separate cohorts planned to receive single doses of 5, 10 and 25 mg itraconzaole, respectively. The study will have an interleaved design; Part 2 will comprise 2 separate cohorts planned to receive daily doses of itraconazole 10 and 20 mg per day for 14 days, respectively. Part 2, Cohort 1 will commence after a review of safety data from Part 1 Cohort 2 suggests it is safe to do so.
Part 3 is a 2-period, randomised, crossover study in adult subjects with mild to moderate stable asthma to assess the safety, tolerability and PK of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and administered as an oral solution (Sporanox® Oral Solution).
- Conditions
- Asthma
- Being tested
- Itraconazole Powder, Itraconazole 200 mg
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Itraconazole PowderDrug
Also called PUR1900
Itraconazole administered as a dry powder for inhalation (PUR1900)
Itraconazole 200 mgDrug
Also called Sporanox®
Sporanox® Oral Solution
| Study group | Role | What they receive |
|---|---|---|
| Part 1 single ascending dose | Experimental | Intervention: drug Itraconzaole powder: single dose of 5mg, 10mg or 25 mg Other name: PUR1900 Receives: Drug: Itraconazole Powder |
| Part 2 multiple ascending dose | Experimental | Intervention: drug Itraconzaole powder: 10 mg or 20 mg daily for 14 days Other name: PUR1900 Receives: Drug: Itraconazole Powder |
| Part 3 2-period crossover single dose | Active comparator | Intervention: drug Itraconzaole powder: 20 mg single dose and Itraconzaole oral solution 200 mg single dose Other names: PUR1900, Sporanox Receives: Drug: Itraconazole Powder; Drug: Itraconazole 200 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0
Safety and tolerability will be assessed by evaluating the number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Secondary outcomes (7)
Area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf) of single dose of itraconazole
The area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf)
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Time of the maximum measured serum concentration (Tmax) of single dose of itraconazole
Time of the maximum measured serum concentration (Tmax)
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Area under the serum concentration vs time curve within the dosing interval (AUCtau) of single dose of itraconazole
The area under the serum concentration vs time curve within the dosing interval (AUCtau)
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent first-order terminal elimination half-life (t1/2 ) of single dose of itraconazole
Apparent first-order terminal elimination half-life (t1/2 )
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the serum concentration vs time curve (Kel) of single dose of itraconazole
Apparent first-order terminal elimination rate constant calculated from a semi-log plot of
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent clearance (CL/F) of single dose of itraconazole
Apparent clearance (CL/F)
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent volume of distribution (Vz/F) of single dose of itraconazole
Apparent volume of distribution (Vz/F)
Measured: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start9 Feb 2018
- Primary completion28 Jun 2018
- Study completion28 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- The study has 3 parts: 1) Single Ascending Dose Escalation and 2) Multiple Ascending Dose Escalation to be conducted in Normal Healthy Volunteers and 3) A two-period crossover study of single doses of PUR1900 and Sporanox in Adults with Asthma
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pulmatrix Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Roach, MD, Study director, Pulmatrix Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03479411
- Sponsor's protocol ID
- 601-0013
- Status last verified
- Jul 2018
- First submitted
- 5 Feb 2018
- Last updated
- 27 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bergagnini-Kolev M, Kane K, Templeton IE, Curran AK. Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data. AAPS J. 2023 Jun 21;25(4):62. doi: 10.1208/s12248-023-00828-z.
PubMed 37344751
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, 3-Part, Open-Label Study to Assess Safety, Tolerability and PK of Single and Multiple Doses of PUR1900 in Healthy Subjects and Crossover Study of Single Doses of PUR1900 and Sporanox in Adult Subjects With Mild to Moderate Asthma
- ClinicalTrials.gov ID
- NCT03479411
- Acronym / sponsor ID
- 601-0013
- Conditions
- Asthma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Pulmatrix Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Feb 2018 (actual)
- Primary completion
- 28 Jun 2018 (actual)
- Study completion
- 28 Jun 2018 (actual)
- First posted
- 27 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1, 3-part study to assess safety, tolerability and PK of single and multiple doses of itraconazole administered as a dry powder for inhalation (PUR1900) in healthy subjects (parts 1 and 2) and a 2-period crossover study of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and an oral solution (Sporanox) in adults with mild to moderate, stable asthma (part 3)
Detailed description
Phase 1, multi-center, 3-part, open-label study in healthy adults (Parts 1 and 2) and adults with mild to moderate, stable asthma (Part 3).
Safety, tolerability and PK will be assessed following either single ascending (SAD) or multiple ascending (MAD) dosing of itraconazole administered as a dry powder for inhalation (PUR1900; Part 1 and Part 2, respectively). Part 1 will comprise 3 separate cohorts planned to receive single doses of 5, 10 and 25 mg itraconzaole, respectively. The study will have an interleaved design; Part 2 will comprise 2 separate cohorts planned to receive daily doses of itraconazole 10 and 20 mg per day for 14 days, respectively. Part 2, Cohort 1 will commence after a review of safety data from Part 1 Cohort 2 suggests it is safe to do so.
Part 3 is a 2-period, randomised, crossover study in adult subjects with mild to moderate stable asthma to assess the safety, tolerability and PK of single doses of itraconazole administered as a dry powder for inhalation (PUR1900) and administered as an oral solution (Sporanox® Oral Solution).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study has 3 parts: 1) Single Ascending Dose Escalation and 2) Multiple Ascending Dose Escalation to be conducted in Normal Healthy Volunteers and 3) A two-period crossover study of single doses of PUR1900 and Sporanox in Adults with Asthma
| Arm | Type | Receives |
|---|---|---|
| Part 1 single ascending dose | Experimental | Drug: Itraconazole PowderIntervention: drug Itraconzaole powder: single dose of 5mg, 10mg or 25 mg Other name: PUR1900 |
| Part 2 multiple ascending dose | Experimental | Drug: Itraconazole PowderIntervention: drug Itraconzaole powder: 10 mg or 20 mg daily for 14 days Other name: PUR1900 |
| Part 3 2-period crossover single dose | Active comparator | Drug: Itraconazole Powder, Drug: Itraconazole 200 mgIntervention: drug Itraconzaole powder: 20 mg single dose and Itraconzaole oral solution 200 mg single dose Other names: PUR1900, Sporanox |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Healthy males or non-pregnant, non-lactating healthy females.
- Age 18 to 60 years
- Screening forced expiratory volume in 1 sec (FEV1) ≥80% of the predicted value
- Screening FEV1/forced vital capacity (FVC) >0.70.
- Able to demonstrate the correct inhalation technique for use of delivery device during the study.
Key exclusion criteria (11 listed)
- Subjects who have received any IMP in a clinical research study within the previous 3 months prior to dosing on this study
- Subjects who have previously received IMP in this study. Subjects who have participated in Part 1 are not permitted to participate in Part 2 or Part 3.
- History of any drug or alcohol abuse in the past 2 years prior to screening.
- Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
- Females of childbearing potential who are pregnant or lactating, or who plan to become pregnant during the study (all female subjects must have a negative pregnancy test at screening). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or is postmenopausal (had no menses for 12 months without an alternative medical cause (will be re-assessed at admission/pre-dose).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Itraconazole PowderAlso: PUR1900Itraconazole administered as a dry powder for inhalation (PUR1900) | Drug | Part 1 single ascending dose, Part 2 multiple ascending dose, Part 3 2-period crossover single dose |
| Itraconazole 200 mgAlso: Sporanox®Sporanox® Oral Solution | Drug | Part 3 2-period crossover single dose |
Primary outcome
Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Safety and tolerability will be assessed by evaluating the number of participants with treatment-related adverse events as assessed by CTCAE v4.0
7 secondary outcomes
Area under the serum concentration vs time curve from time 0 to infinity (AUC0-inf) of single dose of itraconazole
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Time of the maximum measured serum concentration (Tmax) of single dose of itraconazole
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Area under the serum concentration vs time curve within the dosing interval (AUCtau) of single dose of itraconazole
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent first-order terminal elimination half-life (t1/2 ) of single dose of itraconazole
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the serum concentration vs time curve (Kel) of single dose of itraconazole
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent clearance (CL/F) of single dose of itraconazole
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Apparent volume of distribution (Vz/F) of single dose of itraconazole
Time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2018.
- Derived from this study: PubMed 37344751Bergagnini-Kolev M, Kane K, Templeton IE, Curran AK. Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data. AAPS J. 2023 Jun 21;25(4):62. doi: 10.1208/s12248-023-00828-z.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Roach, MD study director
Pulmatrix Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Itraconazole Powder and Itraconazole 200 mg in people with Asthma, run by Pulmatrix Inc. at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0 (time frame: Part 1: Baseline through Day 14, Part 2 and 3: Baseline through Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03479411, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2018.