Minocycline treatment for pulmonary nontuberculous mycobacterial disease

Pharmacokinetic Study of Minocycline in Patients With Pulmonary Nontuberculous Mycobacterial Disease

This study is testing how well the antibiotic minocycline works for people with a lung infection caused by Mycobacterium avium complex when taken with another common medication.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Radboud University Medical Center (Academic / other)
• Locations: 1 site (Nijmegen, Gelderland)
• Trial ID: NCT05861258 on ClinicalTrials.gov

What this trial studies

This study evaluates the pharmacokinetics of minocycline, an antibiotic with potential effectiveness against Mycobacterium avium complex pulmonary disease (MAC-PD). It aims to determine the appropriate dosing of minocycline when used alongside rifampicin, a common treatment for MAC-PD, which can affect drug metabolism. The study is open-label and involves a one-arm, two-period design to assess drug exposure in patients meeting specific diagnostic criteria for MAC-PD. The goal is to improve treatment regimens for patients suffering from this challenging condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who have been diagnosed with pulmonary nontuberculous mycobacterial disease and are eligible for rifampicin-based treatment.

Not a fit: Patients with chronic gastrointestinal, renal, or hepatic diseases, or those diagnosed with cystic fibrosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more effective and tolerable treatment options for patients with pulmonary nontuberculous mycobacterial disease.

How similar studies have performed: While pharmacokinetic studies of antibiotics are common, the specific combination of minocycline and rifampicin in this context is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* 2020 guideline (ATS/ERS/ESCMID/IDSA) diagnostic criteria for nontuberculous mycobacterial pulmonary disease 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 bronchoalveolar lavage culture of the same M. avium complex species.
* At least one of the positive cultures must be done in the last 4 months before inclusion.
* The subject is eligible to start the guideline-recommended rifampicin-based regimen according to the treating physician.
* Age ≥ 18 years.
* Signed and dated patient informed consent.

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, adequate contraceptive measures are abstinence from sexual activities and barrier methods).
* 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 and drugs besides rifampicin that are strong inducers of metabolic enzymes, including barbiturates, carbamazepin and phenytoin (as judged by the investigators).
* 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.

Where this trial is running

Nijmegen, Gelderland

• Radboud University Medical Center — Nijmegen, Gelderland, Netherlands (Recruiting)

Study contacts

• Principal investigator: Wouter Hoefsloot, MSc, PhD — Radboud University Medical Center
• Study coordinator: Arthur Lemson, MSc

Conditions Mycobacterium Avium Complex Pulmonary Disease; Pharmacokinetics; Minocycline; Rifampicin