Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001643369
Ethics application status
Approved
Date submitted
13/11/2017
Date registered
19/12/2017
Date last updated
5/04/2024
Date data sharing statement initially provided
5/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Inhaled rifampicin study in healthy individuals
Scientific title
Inhaled rifampicin safety and dose finding proof of concept study 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
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 at sequential doses starting from 25 mg and higher will be administered to groups 1, 2, 3, 4 and 5 respectively through inhalation route once daily for seven days. The higher doses will include a maximum of 50, 100, 200 and 300 mg of inhaled rifampicin for groups 2, 3, 4 and 5, respectively.
Group 6 will receive oral (standard dose, 600 mg) plus inhaled rifampicin (dose to be determined from pharmacokinetic analysis of data from groups 1-5) 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
There is no control treatment group as this is a phase 1 study. The pharmacokinetic data obtained will be compared with the literature data on pharmacokinetics of oral standard rifampicin.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303929 0
Safety and tolerability assessment by liver function test, pulmonary function test and electrocardiogram (ECG)
Timepoint [1] 303929 0
The primary time point will be of 14 days. Blood samples for liver function test will be collected at baseline, and twice a week during and after drug administration. And pulmonary function tests will also be performed at baseline and twice a week during and after drug administration. ECG test will be performed at baseline and on days 1, 3, 7, 9 and 14 of treatment.
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 and 8 hours.
Secondary outcome [2] 433670 0
Participant reported tolerability measured using participant's responses to questionnaire designed specifically for this study.
Timepoint [2] 433670 0
Secondary outcome [3] 433671 0
Participant reported tolerability measured using participant's responses to questionnaire designed specifically for this study.
Timepoint [3] 433671 0
14 days after the first dose

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.
3. Ability to take oral and inhaled medication
Minimum age
18 Years
Maximum age
55 Years
Sex
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. 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 process.
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
3/02/2025
Actual
Date of last data collection
Anticipated
20/02/2025
Actual
Sample size
Target
50
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
Government body
Name [1] 297968 0
Health Research Council of New Zealand
Country [1] 297968 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
Approved
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
09/11/2023
Approval date [1] 299009 0
23/02/2024
Ethics approval number [1] 299009 0
2024 FULL 18939

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
+64 3 477 6246
Email 78986 0
[email protected]
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 3 556 8539
Fax 78987 0
Email 78987 0
[email protected]
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 3 556 8539
Fax 78988 0
Email 78988 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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.