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Trial registered on ANZCTR


Registration number
ACTRN12618000693224
Ethics application status
Approved
Date submitted
12/04/2018
Date registered
27/04/2018
Date last updated
29/03/2019
Date data sharing statement initially provided
29/03/2019
Date results information initially provided
29/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Investigation of Nasal Deposition using a Medical Device (Nasal Mesh Nebuliser -NMN)
Scientific title
A single center, randomized, controlled, four way cross-over clinical study investigating the deposition of aerosol generated by the Nasal Mesh Nebulizer (NMN) prototype into the nasal cavity using radio-labelled saline at different pulse frequency in healthy volunteers.
Secondary ID [1] 294543 0
AFT-MD-01
Universal Trial Number (UTN)
U1111-1212-1284
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic rhino-sinusitis 307324 0
Condition category
Condition code
Respiratory 306432 306432 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is the treatment of a single intranasal dose of 2ml radio-labelled saline (an isotonic saline solution will be mixed and delivered together with the technetium labelled diethylene triamine petaacetic acid (99m Tc-DTPA). delivered by a nasal mesh nebulizer (NMN) device applied to both nostrils (starting with left nostril and the alternating both nostrils) at different pulse frequencies under the supervision of the study staff:
Treatment A; No pulse (continuous mode)
Treatment B: 10 Hz pulse
Treatment C: 50 Hz pulse
Treatment D: 100 Hz pulse

Between each two treatments, there will be at least 72 -hours washout period.
Participants will receive each treatment in a cross-over way.

For each eligible subject, they will be randomly allocated to a treatment sequence. according to the site master randomization list kept by the study staff.

The healthy subject will be trained by the site staff to use the medical device, and then the subject will administer the treatment under the site staff's supervision (different pulse frequency has already been programmed and labelled for each medical device-the site staff will supply the medical device with the correct pulse frequency labelled to the subject).

The treatment administration will alternate between left and right nostrils (the device will be activated by exhaling and deliver the aresol) -starting with the left nostril and continue the administration until a " beep" like sound will be heard (approximately 20 times of breathing).

To complete all the four study periods and the follow up, each subject will need about 4 weeks to complete the study.
Intervention code [1] 300872 0
Treatment: Devices
Comparator / control treatment
Treatment A No Pulsing (0 Hz)
Control group
Active

Outcomes
Primary outcome [1] 305491 0
The primary endpoint is a composite outcome that the total area of distribution (mm2) of radio-labelled saline immediately after the administration by the NMN (t0) in the different regions of the sinus cavity (Maxillary, frontal, ethmoidal, sphenoidal).

Timepoint [1] 305491 0
T0-immediately after the administration
Secondary outcome [1] 345439 0
The clearance of the radio-labelled saline over 1 hours (at 0, 20 and 60 minutes post-administration) after its administration assessed by the decrement in total radioablled saline between T0, T20 and T60. Clearance will be evaluated for each subiste and compared between treatments (A-D).
Timepoint [1] 345439 0
T0-immediately after the administration
T20-20 minutes after the administration
T60-60 minutes after the administration
Secondary outcome [2] 345440 0
The retention of radio-labelled saline (Area under the curve between T0 and T6) by assessing:
the Total area of deposition of radio-labelled saline
Timepoint [2] 345440 0
T0-immediately after the administration
T60-60 minutes after the administration
Secondary outcome [3] 345441 0
Safety Assessment: Adverse events (AEs) will be collected (including subject-reported AEs during the follow up phone call contact or direct observation during the site visit) for all randomized participants (from receiving the first treatment to the end of follow up) and will be listed with
-type of AE,
-severity
-relationship for each treatment group.
Adverse events data will be summarized for each treatment groups using frequencies and percentages (% of participants with each specific AE)

The anticipated adverse events related to the device may include mild discomfort during the treatment (such as mild nose irritation).
Timepoint [3] 345441 0
AEs will be monitored throughout the study alone with a 24 hour follow up after each treatment.
Secondary outcome [4] 345804 0
The retention of radio-labelled saline (Area under the curve between T0 and T6) by assessing the intensity of radio-labelled saline
Timepoint [4] 345804 0
T0-immediately after the administration
T60-60 minutes after the administration

Eligibility
Key inclusion criteria
Healthy Caucasian male
Aged >20 years
No history of smoking
No history of chronic lung diseases including asthma, cystic fibrosis, tuberculosis, chronic obstructive lung disease
Normal lung function with stable and reproducible baseline FEV1 of > 80% of predicted value following adjustment for height, age and gender according to the Global Lung Initiative equation.
No history of chronic sinusitis or rhinitis
Agree that CT scan data can be used post-study to generate an anatomically correct model of the upper respiratory tract
Minimum age
20 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Significant upper and lower respiratory infection within the previous 4 weeks
History of chronic sinusitis or rhinitis
History of recurrent lung infections.
History of chronic lung diseases
History of severe or multiple allergies, including hay-fever and perennial rhinitis
History of nasal fracture, nasal deformities or nasal polyps
History of disease, surgery, or abnormality of the upper respiratory tract, especially the nasal cavity.
History of significant nose bleeds
Participants using topical nasal medication e.g. decongestant, within the last 14 days of the first study day
Participants unable to perform pulmonary function test according to ATS/ERS criteria
Participants with documented or suspected, clinically significant alcohol or drug abuse
Current malignant or cardiovascular disease
Any serious or active medical or psychiatric illness
Current smokers, i.e. those who had smoked within the last 12 months and 6 hours prior to the scan. A negative Cotinine test must be demonstrated at each visit.
Participants who have any non-removable metal objects such as pacemakers, insulin/infusion pumps, cochlear and ear implant, metal plates, screws etc. in their head, neck, chest or abdominal area that may interfere with the /PET/SPECT/CT.
Nasal jewellery or nasal piercing
Participants with tattoos or permanent makeup above shoulder
Participants for whom participation in this study will exceed the limit of total radiation exposure allowed in any 12 months period (5 mSv), or will exceed 10 mSv over the last five-year period

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed (open label)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using a randomization table generated by the study statistician via computerized sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Nil
Phase
Phase 1
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary endpoint of this study is the total area of distribution (mm2) of radiolabelled saline immediately after administration by the NMN (T0). This will be evaluated for each of subsites (surgically expanded ostia of the paranasal sinuses and oropharynx) and compared between treatments (A-D) which correspond to the different pulse frequencies tested. Between-treatment differences in total area of deposition of radiolabelled saline at each subsite will be compared by means of one-way analysis of variance (ANOVA) with application method as a factor.
Pairwise comparisons will be performed between each of the pulsed application methods and the continuous application (no pulse). Pairwise comparisons will be tested using a two-tailed p-value of <0.05.
Clearance will be calculated by the decrement in total radiolabelled saline between T0,, T2 0and T60. Clearance will be evaluated for each subsite and compared between treatments (A-D). As with the primary efficacy endpoint, between-treatment differences in radiolabelled clearance will be tested by means of one-way analysis of variance (ANOVA) with application method as a factor. Pair-wise comparisons will be made between each of the pulsed application methods and the continuous application (no pulse).
The retention of radiolabelled saline will be evaluated as the Area Under the Curve between T0 and T60 (AUC0-60) of the following assessments:
-the total area of deposition of radiolabelled saline
-the intensity of radiolabelled saline
The AUCs will be evaluated for each subsite and compared between treatments (A-D). Between-treatment differences in AUCs will be tested by means of one-way analysis of covariance (ANCOVA) with application method as a factor and the value at T0 as covariate. Pair-wise comparisons will be made between each of the pulsed application methods and the continuous application (no pulse).

Recruitment
Recruitment status
Active, not recruiting
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)
NSW
Recruitment hospital [1] 10637 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 22356 0
2065 - St Leonards
Recruitment postcode(s) [2] 22357 0
2065 - Royal North Shore Hospital

Funding & Sponsors
Funding source category [1] 299167 0
University
Name [1] 299167 0
Woolcock Institute of Medical Research
Address [1] 299167 0
431 Glebel Point Road, Glebe NSW 2037
Country [1] 299167 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
AFT Pharmaceuticals Ltd.
Address
Level 1, 129 Hurstmere Road, Takapuna, Auckland, 0622, New Zealand
Country
New Zealand
Secondary sponsor category [1] 298461 0
None
Name [1] 298461 0
Address [1] 298461 0
Country [1] 298461 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300092 0
Human Research Ethics Committee-Northern Sydney Local Health District
Ethics committee address [1] 300092 0
Kolling Building, Level 13
Royal North Shore Hospital
St Leonards NSW 2065
Australia
Tel: (02) 9926 4590
Fax: (02) 9926 6179
Ethics committee country [1] 300092 0
Australia
Date submitted for ethics approval [1] 300092 0
27/06/2016
Approval date [1] 300092 0
24/10/2016
Ethics approval number [1] 300092 0
HREC/16/HAWKE/256

Summary
Brief summary
This is an exploratory study using a new clinical NMN prototype to determine the regional depositions in the nasal cavity of aerosols using different pulse frequency modes in healthy volunteers.
The main objective of the study is to determine the optimal frequency for the NMN that will provide the basis for future in vivo sinus targeting of drug delivery systems. The primary endpoint of this study is the total area of distribution (mm2) of radiolabelled saline immediately after administration by the NMN (T0) in the different regions of the sinus cavity.
Trial website
Not applicable
Trial related presentations / publications
Not applicable
Public notes
Attachments [3] 2590 2590 0 0

Contacts
Principal investigator
Name 82542 0
A/Prof Gregory King
Address 82542 0
Department of Respiratory Medicine
Royal North Shore Hospital
Pacific Highway
St Leonards, NSW 2065
Australia
Country 82542 0
Australia
Phone 82542 0
+ 61 2 9463 2935
Fax 82542 0
Email 82542 0
gregory.king@sydney.edu.au
Contact person for public queries
Name 82543 0
Dr Maliheh Ghadiri
Address 82543 0
Discipline of Pharmacology | Sydney Medical School| Woolcock Institute of Medical Research|

THE UNIVERSITY OF SYDNEY

431 Glebe Point Road | Glebe | NSW | 2037
Country 82543 0
Australia
Phone 82543 0
+61 2 91140366
Fax 82543 0
Email 82543 0
maliheh.ghadiri@sydney.edu.au
Contact person for scientific queries
Name 82544 0
Dr Maliheh Ghadiri
Address 82544 0
Discipline of Pharmacology | Sydney Medical School| Woolcock Institute of Medical Research|

THE UNIVERSITY OF SYDNEY

431 Glebe Point Road | Glebe | NSW | 2037
Country 82544 0
Australia
Phone 82544 0
+61 2 91140366
Fax 82544 0
Email 82544 0
maliheh.ghadiri@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Statistical analysis will be conducted for the data collected from all the 11 participants enrolled. Presenting individual participant data is not making sense.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary