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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04576325




Registration number
NCT04576325
Ethics application status
Date submitted
25/09/2020
Date registered
6/10/2020
Date last updated
1/04/2021

Titles & IDs
Public title
Pharmacokinetic Profile of Voriconazole Inhalation Powder in Adult Subjects With Asthma
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetic Profile of Voriconazole Inhalation Powder in Adult Subjects With Asthma
Secondary ID [1] 0 0
TFF-V1-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Voriconazole Inhalation Powder
Treatment: Drugs - Placebo

Experimental: Voriconazole Inhalation Powder - Investigational drug will be supplied as capsules, each capsule contains 10 mg of Voriconazole Inhalation Powder. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.

Placebo Comparator: Placebo - Placebo will be supplied as capsules, each capsule will contain no active ingredient. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.


Treatment: Drugs: Voriconazole Inhalation Powder
For each dose, multiple inhalations will be required (4 capsules in Cohort 1 and 8 capsules in Cohort 2). All capsules for a given dose must be inhaled over a maximum 10-minute period. Cohort 1 will receive 40 mg BID and Cohort 2 will receive 80 mg BID. Both Cohorts will administer study drug for 3.5 days (7 days total).

Treatment: Drugs: Placebo
For each dose, multiple inhalations will be required (4 capsules in Cohort 1 and 8 capsules in Cohort 2). All capsules must be inhaled over a maximum 10-minute period. Cohort 1 will receive 4 capsules of inactive BID and Cohort 2 will receive 8 capsules of inactive BID. Both Cohorts will administer placebo capsules for 3.5 days (7 days total).

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants who experience Adverse Events (AEs), Serious Adverse Events (SAEs) and withdrawals due to AEs - Frequency of AEs, SAEs, and discontinuations due to AEs
Timepoint [1] 0 0
Through study completion, an average of 14 days
Primary outcome [2] 0 0
Number of participants who experience vital sign abnormalities - Number of participants with potentially clinically significant vital sign values
Timepoint [2] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [3] 0 0
Number of participants who experience pulse oximetry abnormalities - Number of participants with potentially clinically significant pulse oximetry values
Timepoint [3] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [4] 0 0
Mean change from baseline in forced expiratory volume (FEV1) - Spirometry used to measure FEV1 lung function
Timepoint [4] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [5] 0 0
Mean change from baseline in forced vital capacity (FVC) - Spirometry used to measure FVC lung function
Timepoint [5] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [6] 0 0
Mean change from baseline in forced expiratory flow over the middle 1/2 of the FVC (FEF25-75%) - Spirometry used to measure FVC and FEF25-75% lung function
Timepoint [6] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [7] 0 0
Mean change from baseline in FEV1/FVC ratio - Spirometry used to measure FEV1 and FVC lung function
Timepoint [7] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [8] 0 0
Mean change from baseline in QTcF changes via ECG - Number of participants with potentially clinically significant ECG values
Timepoint [8] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [9] 0 0
Number of participants who experience physical examination abnormalities - Number of participants with potentially clinically significant physical examination findings
Timepoint [9] 0 0
Baseline through study completion, an average of 14 days
Primary outcome [10] 0 0
Number of participants who experience laboratory test abnormalities - Number of participants with potentially clinically significant laboratory test results
Timepoint [10] 0 0
Baseline through study completion, an average of 14 days
Secondary outcome [1] 0 0
PK of VIP in plasma: Area under the plasma-concentration time curve (AUC) - Blood samples will be collected for plasma analysis
Timepoint [1] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [2] 0 0
PK of VIP in plasma: Area under the plasma-concentration time curve over the first 12 hours after dosing (AUC0-12) - Blood samples will be collected for analysis
Timepoint [2] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [3] 0 0
PK of VIP in plasma: Area under the concentration time curve, from time 0 to the last observed non-zero concentration (AUC0-tlast) - Blood samples will be collected for analysis
Timepoint [3] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [4] 0 0
PK of VIP in plasma: Area under the concentration time curve from time 0 extrapolated to infinity (AUC8) - Blood samples will be collected for analysis
Timepoint [4] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [5] 0 0
PK of VIP in plasma: Maximum observed concentration (Cmax) - Blood samples will be collected for analysis
Timepoint [5] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [6] 0 0
PK of VIP in plasma: Time to maximal observed concentration (tmax) - Blood samples will be collected for analysis
Timepoint [6] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [7] 0 0
PK of VIP in plasma: Termination elimination half-life (t½) - Blood samples will be collected for analysis
Timepoint [7] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [8] 0 0
PK of VIP in plasma: Apparent total body clearance (CL/F) - Blood samples will be collected for analysis
Timepoint [8] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)
Secondary outcome [9] 0 0
PK of VIP in plasma: Apparent volume of distribution during the terminal elimination phase (Vz/F) - Blood samples will be collected for analysis
Timepoint [9] 0 0
Predose Day 1 and through 12 hours post last dose (day 4)

Eligibility
Key inclusion criteria
1. Provide written informed consent to participate and is willing and able to participate
in the study and abide by study restrictions in the judgement of the Investigator.

2. Males or non-pregnant, non-lactating females.

3. Well-controlled Step 2 or Step 3 asthma defined by the GINA guidelines.

4. Body mass index (BMI) = 18.0 and = 35.0 kg/m2 at Screening.

5. Normal blood pressure at Screening and Check-In.

6. Normal clinical laboratory tests at Screening and Check-In.

7. Negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody, human
immunodeficiency virus (HIV) I and II antibodies, tuberculosis (TB), or COVID-19 at
Screening.

8. Able to successfully perform spirometry and use the inhalation device, as demonstrated
at Screening and Check-In.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History or presence of clinically significant medical, ophthalmic, or psychiatric
conditions or diseases in the opinion of the Investigator or designee.

2. History or current evidence of any chronic upper or lower respiratory conditions other
than asthma or allergic (seasonal or perennial), or non-allergic rhinitis. History of
mild acute upper or lower respiratory conditions are allowed, provided that it has
been at least 3 months since the condition resolved and provided that in the
Investigator's judgement, this occurrence poses no additional risk for this subject.

3. History of any illness or surgery within 6 months of Screening that, in the opinion of
the Investigator, might confound the results of the study or that poses an additional
risk to the subject by their participation in the study.

4. Current or former smokers, users of e-cigarettes or nicotine replacement products who
have more than a 10-pack year history of smoking and who have used these products
within the 6 months prior to Screening.

5. History or presence of alcoholism or drug abuse within the past 2 years prior to
Screening.

6. History or presence of hypersensitivity or idiosyncratic reaction to voriconazole or
any triazole antifungal.

7. Received any marketed or investigational biologic within 4 months or 5 half-lives
prior to dosing, whichever is longer.

8. Received treatment with investigational study drug (or device) in another clinical
study within 30 days or five half-lives of dosing, whichever is longer.

9. Subjects who have taken any of the protocol prohibited medications within 30 days of
the first dose or who are expected to require these medications during the study.

10. ECG with a QTcF interval >450 msec for males or QTcF interval > 470 msec for females
or ECG findings deemed clinically significantly abnormal by the Investigator prior to
the first dose.

11. Unable to refrain from or anticipates the use of any vitamin supplements,
prescription, over-the-counter (OTC), herbal preparations or medications other than
those specified for asthma or allergic rhinitis medications, or topical ophthalmic
drops beginning 14 days prior to the first dose and throughout the study.

12. Females requiring hormone replacement therapy within 30 days of Screening or during
the study.

13. Allergy or sensitivity to lactose or milk products.

14. Donation of blood or blood products within the last 2 months.

15. Loss of 50 to 500 mL whole blood within the past two months.

Study design
Purpose of the study
Basic Science
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Q-Pharm Pty Ltd (Nucleus Networks) - Brisbane
Recruitment postcode(s) [1] 0 0
4006 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
TFF Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1b, randomized, double-blind, placebo-controlled trial to evaluate the
safety, tolerability, and pharmacokinetic profiles of voriconazole inhalation powder in adult
subjects with well-controlled asthma. This study will involve 2 cohorts.
Trial website
https://clinicaltrials.gov/show/NCT04576325
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dale Christensen, PhD
Address 0 0
TFF Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Michelle Widmann
Address 0 0
Country 0 0
Phone 0 0
9196001819
Fax 0 0
Email 0 0
mwidmann@tffpharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04576325