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Trial registered on ANZCTR


Registration number
ACTRN12617001643369p
Ethics application status
Not yet submitted
Date submitted
13/11/2017
Date registered
19/12/2017
Date last updated
19/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Inhaled rifampicin study in healthy individuals
Scientific title
Safety and dose finding study for inhaled rifampicin in healthy volunteers
Secondary ID [1] 293347 0
None
Universal Trial Number (UTN)
U1111-1205-0201
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberculosis 305451 0
Meningitis 305452 0
Condition category
Condition code
Infection 304723 304723 0 0
Other infectious diseases
Respiratory 304777 304777 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Rifampicin dry powder 100 mg, 200 mg and 300 mg will be administered to groups 1, 2 and 3 respectively through inhalation route once daily for seven days.
Drug administration will be witnessed and documented by the site investigator at each dosing.
Intervention code [1] 299599 0
Treatment: Drugs
Comparator / control treatment
Reference group will receive 600 mg rifampicin once daily for seven days, administered through oral route
Control group
Active

Outcomes
Primary outcome [1] 303929 0
Safety and tolerability assessment by liver function test and pulmonary function test
Timepoint [1] 303929 0
The primary time point will be of 14 days. Blood samples for liver function test will be collected twice a week. And pulmonary function tests will also be performed twice a week.
Secondary outcome [1] 340479 0
Pharmacokinetics parameters Cmax, Tmax and AUC will be assessed.
Timepoint [1] 340479 0
The secondary time point is of seven days. The blood samples will be collected for pharmacokinetic assessment on the seventh day at baseline, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours.

Eligibility
Key inclusion criteria
1. Provision of signed and dated informed consent form.
2. In good general health as evidenced by medical history, no current prescription medication usage, normal FEV1 (forced expiratory volume in 1 second, ), FVC (forced vital capacity) values, normal baseline liver function test values.
5. Ability to take oral and inhaled medication
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Current use of prescription medications or use in the past one month
2. Pregnancy or lactation.
3. History of asthma, or past respiratory condition and previous known exposure to TB.
4. Abnormalities on pulmonary function tests on screening and abnormalities in baseline liver function tests with ALT, ALP, BILI values > 3x ULN.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The study will be performed in a sequential manner i.e. reference group and lowest dose inhalation group will participate in and complete the study first, which will be followed by higher inhalation dose groups after a review by an internal data and safety monitoring board.
Phase
Not Applicable
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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 outside Australia
Country [1] 9351 0
New Zealand
State/province [1] 9351 0
Otago

Funding & Sponsors
Funding source category [1] 297968 0
University
Name [1] 297968 0
University of Otago
Address [1] 297968 0
University of Otago, School of pharmacy (18 Frederick Street, Dunedin 9054, New Zealand) will provide in-kind support.
Country [1] 297968 0
New Zealand
Funding source category [2] 298148 0
University
Name [2] 298148 0
Otago respiratory research unit (Dunedin School of Medicine)
Address [2] 298148 0
Dunedin Hospital (PO Box 56, Dunedin 9058, New Zealand) will provide clinic facilities for the study.
Country [2] 298148 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
School of Pharmacy
University of Otago
18 Frederick street
North Dunedin
Dunedin Otago 9016
Country
New Zealand
Secondary sponsor category [1] 297236 0
None
Name [1] 297236 0
Address [1] 297236 0
Country [1] 297236 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 299009 0
Health and Disability Ethics Committee
Ethics committee address [1] 299009 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 299009 0
New Zealand
Date submitted for ethics approval [1] 299009 0
15/01/2018
Approval date [1] 299009 0
Ethics approval number [1] 299009 0

Summary
Brief summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a disease mainly of the lungs. Rifampicin, a first-line anti-TB medicine, is given orally for 6 months, and only a small fraction of the dose goes to the lung. Direct delivery of rifampicin to the lungs by inhalation can achieve high drug levels in the lung and in blood to kill M. tuberculosis more effectively throughout the body.This is a proof of concept study in healthy human participants to confirm safety and determine the optimal dose for inhalation. This will enable design of clinical studies combining inhaled and oral rifampicin in TB patients. Adjunct inhaled rifampicin combined with standard oral dose rifampicin has potential to change the way TB is managed worldwide by offering the prospect of a shortened treatment course from 6 months to 3-4 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78986 0
Dr Jack Dummer
Address 78986 0
Department of Medicine
University of Otago
PO Box 56, Dunedin 9054
Country 78986 0
New Zealand
Phone 78986 0
+64 3 470 9362
Fax 78986 0
Email 78986 0
jack.dummer@otago.ac.nz
Contact person for public queries
Name 78987 0
Mr Prakash Khadka
Address 78987 0
School of Pharmacy
University of Otago
PO Box 56, Dunedin 9054
Country 78987 0
New Zealand
Phone 78987 0
+64 3 479 5285
Fax 78987 0
Email 78987 0
khapr090@student.otago.ac.nz
Contact person for scientific queries
Name 78988 0
Mr Prakash Khadka
Address 78988 0
School of Pharmacy
University of Otago
PO Box 56, Dunedin 9054
Country 78988 0
New Zealand
Phone 78988 0
+64 3 479 5285
Fax 78988 0
Email 78988 0
khapr090@student.otago.ac.nz

No data has been provided for results reporting
Summary results
Not applicable