Minocycline use in pulmonary infections with mycobacterium avium complex

Phase 1

• Conditions: Pulmonary disease caused by Mycobacterium avium complex. Mycobacterium avium complex is a nontuberculous mycobacterium.; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2019-000938-20-NL
• Lead Sponsor: Radboudumc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-04-08
• Last Update Posted: 26 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

- ATS diagnostic criteria for NTM-PD are met, i.e. the patient is symptomatic, has nodules, bronchiectasis or fibro-cavitary lesions seen on (HR)CT scan of the lungs and =2 positive sputum cultures or one positive BAL culture of the same M. avium complex species.
- The subject is eligible to start the guideline-recommended rifampicin-based regimen according to the treating physician.
- At least one of the positive cultures must be done in the last 4 months before inclusion.
- Age = 18 years.
- Signed and dated patient informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

- A relevant medical history or current condition that might interfere with drug absorption, distribution, metabolism or excretion (i.e. chronic gastro-intestinal disease, renal or hepatic disease).
- Diagnosed with cystic fibrosis (as this may affect the pharmacokinetics of drugs).
- Pregnant or breastfeeding (contra-indications for minocycline) or inadequate contraceptive measures (in view of the administration of rifampicin which interacts with oral contraceptive drugs).
- Use of drugs that cause a relevant drug interaction with minocycline, i.e. oral magnesium, bismuth, aluminium, calcium, zinc or iron containing formulations (antacid drugs, multivitamin and mineral-containing drugs) and other drugs besides rifampicin that induce metabolic enzymes, including but not limited to barbiturates, carbamazepin and phenytoin. The investigators refer to the ‘Flockhart’table for check of presence of possible inducers (https://drug-interactions.medicine.iu.edu/Main-Table.aspx).
- ALAT > 3 times the upper limit of normal (normal <45 U/l).
- ASAT > 3 times the upper limit of normal (normal <35 U/l).
- An abnormal serum creatinine level (defined as a level that is higher than the upper limit of normal, i.e. >110 umol/l).
- Active alcohol abuse.
- Hypersensitivity to minocycline or to other tetracycline antibiotics.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To describe the pharmacokinetics of a single dose of minocycline in patients with M. avium complex pulmonary disease.;Secondary Objective: To evaluate the effect of rifampicin on the pharmacokinetics of a single dose of minocycline in patients with MAC-PD. ;Primary end point(s): Total exposure (area under the concentration versus time curve from T=0 up to infinity, after a single dose of minocycline, AUC0-8) and peak serum concentration (Cmax) of minocycline before and after start of a rifampicin containing regimen.;Timepoint(s) of evaluation of this end point: Blood is taken before and after both single doses of minocycline. Blood is taken for pharmacokinetic sampling at t=0 (before minocycline intake), 1, 2, 3, 4, 8, 24, 48 hours. Pharmacokinetic parameters are calculated by applying standard noncompartmental pharmacokinetic data analyses.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Other pharmacokinetic parameters of minocycline, i.e. clearance, volume of distribution and half-life to the given dosage before and after start of a rifampicin containing regimen<br>- Pharmacokinetic parameters of rifampicin.<br>- A population PK model of minocycline suitable for dosing regimen simulations<br>;Timepoint(s) of evaluation of this end point: Blood is taken before and after both single doses of minocycline. Blood is taken for pharmacokinetic sampling at t=0 (before minocycline intake), 1, 2, 3, 4, 8, 24, 48 hours. Pharmacokinetic parameters are calculated by applying standard noncompartmental pharmacokinetic data analyses.