None listed
Conditions
Brief summary
It is estimated that in Australia 12% of cystic fibrosis patients are infected with Mycobacterium abscessus, a non-tuberculous mycobacteria (NTM) which is associated with a decline in lung function and increased mortality. Treatment is expensive, toxic and is unsuccessful in most patients. Mycobacterium abscessus is found more commonly in CF patients from Queensland than from more temperate southern states. Another common NTM infection is Mycobacterium avium-intracellulare which has a better cure rate however treatment is for at least twelve months and requires multiple antibiotics some of which cannot be used with newer gene therapies for CF. Despite this being a research priority in CF there have been no randomised trials carried out to determine optimum therapy. In the absence of these clinical trials, pharmacokinetics – the study of how drugs move through the body - is a key means of discovering the best dose to use in different groups. We believe that the current doses of mycobacterial drugs being used in CF are too low and may be contributing to high rates of treatment failure. We will test the blood levels of important drugs given to patients with CF with NTM infection and compare to the drug levels in people without cystic fibrosis published in other studies. In this way we can help determine whether the doses we are using are correct or need to be changed. If the doses of antibiotics being used in CF are too low this could lead to new dosing regimens being used in future drug trials.
Interventions
To describe first dose pharmacokinetics of antimycobacterials in cystic fibrosis (CF) patients including rifampicin, ethambutol, minocycline, clofazimine, azithromycin and clarithromycin. This study will be in subjects who do not have mycobacterial infection.
Unless contraindicated based on allergies, potential drug-drug interactions or other exclusions subjects will receive single concurrent oral doses of (1) rifampicin 600mg tablet, (2) ethambutol 15 mg/kg tablet, (3) clofazimine 100mg tablet
To describe first dose pharmacokinetics of antimycobacterials in cystic fibrosis (CF) patients including rifampicin, ethambutol, minocycline, clofazimine, azithromycin and clarithromycin. This study will be in subjects who do not have mycobacterial infection. Unless contraindicated based on allergies, potential drug-drug interactions or other exclusions subjects will receive single concurrent oral doses of (1) rifampicin 600mg tablet, (2) ethambutol 15 mg/kg tablet, (3) clofazimine 100mg tablet, (4) minocycline 200mg tablet, and either (5) clarithromycin 500mg tablet or (6) azithromycin 500mg tablet. If a subject is already on long term azithromycin for biofilm inhibition then they will receive clarithromycin. If they are not on azithromycin they will receive azithromycin as a study drug. This will be determined by chief investigator. Study drugs will be administered by a registered nurse. Subjects will then have intensive plasma sampling to allow for pharmacokinetic analysis.
Sponsors
University of Queensland
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Age greater or equal to 18 years and able to give consent or under 18 with the consent of a substitute decision maker. • A negative screen for mycobacteria within the last 6 months for those who are being given a single dose of antibiotics. • Availability of suitable intravenous access to facilitate sample collection • Written informed consent has been obtained from the patient or substitute decision maker (according to local regulatory statements for ethical conduct of research at each study site) • able to tolerate full diet without nasogastric or PEG feeding
Exclusion criteria
• Known adverse reaction to anti-mycobacterial drug being used in study • On a non-study drug which may have clinically significant interactions with study drug • Unavailability of intravenous access device for blood collection • Treating clinicians concerns that the total of volume of blood to be collected may be worsen pre-existing anaemia defined as haemoglobin < 70 g/L. • Abnormal liver function, at screening, defined as greater than or equal to (>=) 3 time upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), total bilirubin • Renal impairment with eGFR less than 30 mls/min • Prolonged QTc of >500ms on ECG or history of cardiac arrhythmia
Outcome results
None listed