None listed
Conditions
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.
Interventions
Rifampicin solution for nebulisation 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 se
Rifampicin solution for nebulisation 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.
Sponsors
University of Otago
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
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.
Outcome results
None listed