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Trial registered on ANZCTR


Registration number
ACTRN12620000192987
Ethics application status
Approved
Date submitted
5/02/2020
Date registered
19/02/2020
Date last updated
12/07/2023
Date data sharing statement initially provided
19/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized, Single-Dose and Multiple Dose Dose-Ranging Safety and Pharmacokinetics Study of Tacrolimus Powder for Inhalation in Healthy Adult Subjects
Scientific title
A Randomized, Single-Dose and Multiple Dose Dose-Ranging Safety and Pharmacokinetics Study of Tacrolimus Powder for Inhalation in Healthy Adult Subjects
Secondary ID [1] 300318 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prophylactic therapy of organ rejection in patients receiving allogeneic lung transplants 315923 0
Condition category
Condition code
Respiratory 314195 314195 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 314230 314230 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part A:
This is a double-blinded, placebo-controlled, randomized, dose-ranging study evaluating five different dose levels (0.5, 1.0, 2.5, 5, and 10 mg).

On Day 1 of each period, subjects will receive a single dose of either TFF tacrolimus inhalation powder or a matching placebo. Participants will receive only one dose level of TFF tacrolimus. Participants will be required to fast overnight prior to dosing and for 2 hours following dosing, and will be domiciled at the clinical research center. Treatments will be administered by the clinic staff.

For the 2.5 mg dose level, subjects will be given two administrations, one fasted and one with a high fat meal (50%-60% fat), in a fixed sequence fashion separated by one week. Safety and PK will be monitored on both occasions.

Part B:
This is a double-blinded, placebo-controlled, randomized, multi-dose study evaluating three different dose levels (1.0, 2.5, and 5.0 mg BID). Participants who enrolled in Part A are not eligible to enroll in Part B.

Tacrolimus inhalation powder or matching placebo will be administered twice per day for 6.5 days for a total of 13 doses. Participants will receive only one dose level of TFF tacrolimus.
Participants will be domiciled at the clinical research center and treatments will be administered by the clinic staff.
Intervention code [1] 316594 0
Prevention
Comparator / control treatment
5 mg lactose monohydrate for inhalation
Control group
Placebo

Outcomes
Primary outcome [1] 322575 0
Part A:
To evaluate the safety and tolerability of a single inhalation dose of TFF tacrolimus administered in a dose-ranging sequence

Part B:
To evaluate the safety and tolerability of a multi-dose regimen of inhaled TFF tacrolimus

Safety and tolerability will be assessed using clinical labs, pulmonary function testing, cardiac monitoring, and physical examination for Part A and Part B.
Timepoint [1] 322575 0
Part A:
Day 3

Part B:
Day 9
Primary outcome [2] 322576 0
Part A:
To evaluate the pharmacokinetics (PK) of a single inhalation dose of TFF tacrolimus administered in a dose-ranging sequence

Part B:
To evaluate the pharmacokinetics (PK) of multidose inhalation TFF tacrolimus administered in a multiple dose dose-ranging sequence

Pharmacokinetic outcomes will be assessed using Tmax, Cmax, T 1/2, and AUC for both Part A and Part B.
Timepoint [2] 322576 0
Part A;
Peak, trough, other pharmacokinetic measures of blood levels of drug

Blood draws will be performed at the following timepoints for Part A: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 20, 24, 36, 48 hours.

Part B:
Peak, trough, other pharmacokinetic measures of blood levels of drug

Blood draws will be performed at the following timepoints for Part B Day 1: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 20, 24, 36, 48 hours.
On Day 7 blood draws will be performed at the following timepoints: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 20, 24, 36, 48 hours.
Secondary outcome [1] 378976 0
Nil
Timepoint [1] 378976 0
Nil


Eligibility
Key inclusion criteria
1. Healthy, adult, male or female (women of non-child bearing potential only),
2. Continuous non smoker who has not used nicotine containing products (including e vaping) for at least 3 months prior to the first dosing and throughout the study, based on subject’s self-reporting and urine cotinine levels at screening.
3. Medically healthy with no clinically significant medical history, physical and neurologic examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
4. A CKD-EPI Creatinine 2009 estimated creatinine clearance of >=80 mL/min
5. A non vasectomized, male subject must agree to use a highly effective method of birth control with female partners of childbearing potential during the study and for 120 days following dosing.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
2. History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
3. History or presence of hypersensitivity or idiosyncratic reaction to tacrolimus, cyclosporine, or any chemically related compound (everolimus, sirolimus).
4. History of lactase deficiency
5. Has had surgery or any medical condition within 6 months prior to first dosing which may affect the absorption, distribution, metabolism, or elimination of the study drug, in the opinion of the PI or designee.
6. Female subjects with a positive pregnancy test or who are lactating.
7. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
8 ECG findings are abnormal.
9. Blood pressure is abnormal.
10. Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.

Study design
Purpose of the study
Prevention
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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
WIthin each cohort of the study, 6 subjects will be randomized to receive tacrolimus and the other 2 subjects will receive placebo.
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/03/2020
Actual
29/06/2020
Date of last participant enrolment
Anticipated
16/11/2020
Actual
10/08/2021
Date of last data collection
Anticipated
18/11/2020
Actual
19/08/2021
Sample size
Target
64
Accrual to date
Final
64
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 17534 0
Nucleus Network - Melbourne
Recruitment hospital [2] 17535 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 31267 0
4006 - Herston
Recruitment postcode(s) [2] 31268 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 304743 0
Commercial sector/Industry
Name [1] 304743 0
TFF Pharmaceuticals Australia Pty Limited
Country [1] 304743 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
TFF Pharmaceuticals Australia Pty Limited
Address
Level 20, Suite 2003,
109 Pitt Street
SYDNEY NSW 2000
Country
Australia
Secondary sponsor category [1] 305056 0
None
Name [1] 305056 0
Address [1] 305056 0
Country [1] 305056 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305163 0
Alfred Hospital Human Research Ethics Comittee
Ethics committee address [1] 305163 0
Ethics committee country [1] 305163 0
Australia
Date submitted for ethics approval [1] 305163 0
15/05/2020
Approval date [1] 305163 0
29/05/2020
Ethics approval number [1] 305163 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 99450 0
Dr Jason Lickliter
Address 99450 0
Centre for Clinical Studies at Nucleus Network Pty. Ltd.,
Level 5, Burnet Tower, 89 Commercial Rd
Melbourne, VIC 3004
Country 99450 0
Australia
Phone 99450 0
+61 3 9089 8236
Fax 99450 0
Email 99450 0
[email protected]
Contact person for public queries
Name 99451 0
Jason Lickliter
Address 99451 0
Centre for Clinical Studies at Nucleus Network Pty. Ltd.,
Level 5, Burnet Tower, 89 Commercial Rd
Melbourne, VIC 3004
Country 99451 0
Australia
Phone 99451 0
+61 3 9089 8236
Fax 99451 0
Email 99451 0
[email protected]
Contact person for scientific queries
Name 99452 0
Jason Lickliter
Address 99452 0
Centre for Clinical Studies at Nucleus Network Pty. Ltd.,
Level 5, Burnet Tower, 89 Commercial Rd
Melbourne, VIC 3004
Country 99452 0
Australia
Phone 99452 0
+61 3 9089 8236
Fax 99452 0
Email 99452 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data cannot be shared because this information will be included in a new drug application approval. This study is also being conducted under a US IND, therefore the data needs to be kept with the filing, however any significant safety information will be shared in order for study subject to follow up with personal physician.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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