Pharmacokinetic Study of Minocycline in Patients With Pulmonary Nontuberculous Mycobacterial Disease

NCT05861258 | Terminated Phase 2

• 1 other identifier: NL69313.091.19
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Antimycobacterial treatment of M. avium complex pulmonary disease (MAC-PD) has suboptimal cure rates and is challenging due to frequent adverse drug reactions and drug-drug interactions. Hence, there is an urgent need for improved treatment regimens with effective and tolerable antibiotics. Minocycline is a well-tolerated, orally administered tetracycline-type antibiotic with in vitro activity against MAC, but pharmacokinetic data in the target population is lacking. Moreover, rifampicin, a strong inducer of cytochrome P450 enzymes involved in drug metabolism and of various drug transporters, is part of the current first-line MAC-PD treatment regimen and has a substantial interaction with doxycycline, a related tetracycline. Pharmacokinetic data in the target population will allow us to propose an appropriate dose of minocycline when co-administered with or without rifampicin Mino-PK is an open label, one-arm, two-period, fixed-order pharmacokinetic study that will assess exposure to minocycline in MAC-PD patients with and without concurrent use of rifampicin. Subjects will receive two 5-day dosing periods of minocycline; the first without and second with concurrent use of rifampicin. Minocycline plasma concentrations will be determined after both dosing periods.

Conditions

Mycobacterium Avium Complex Pulmonary Disease

Keywords

Pharmacokinetics; Minocycline; Rifampicin

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.

  The area under the curve (AUC0-24h)

  Day 5 of the first minocycline dosing period

• Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.

  The peak plasma concentration (Cmax)

  Day 5 of the first minocycline dosing period

• Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.

  The plasma trough concentration (Cmin)

  Day 5 of the first minocycline dosing period

Secondary Outcomes (5)

• Pharmacokinetic parameters of minocycline in MAC-PD patients with concurrent use of rifampicin.

  Day 5 of the second minocycline dosing period

• Pharmacokinetic parameters of minocycline in MAC-PD patients with concurrent use of rifampicin.

  Day 5 of the second minocycline dosing period

• Pharmacokinetic parameters of minocycline in MAC-PD patients with concurrent use of rifampicin.

  Day 5 of the second minocycline dosing period

• Pharmacokinetic parameters of rifampicin in MAC-PD patients

  Day 5 of the second minocycline dosing period

• Adverse Events

  Through study completion, an average of 6 weeks

Interventions

Minocycline DRUG

Patients with M. avium complex pulmonary disease will receive 200 mg of minocycline for 5 days before starting rifampicin and after 1 month (±1 week) of receiving rifampicin. Antimycobacterial drugs other than rifampicin can be started prior to or simultaneous with the first minocycline dosing period as part of standard care. At day 5 of both minocycline dosing periods, blood will be sampled for minocycline plasma concentration measurements at T = 0, 1, 2, 3, 4, 6, 8 and 24 hours.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud University Medical Center

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (1)

• Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ Jr, Andrejak C, Bottger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020 Jul 7;56(1):2000535. doi: 10.1183/13993003.00535-2020. Print 2020 Jul.

  PMID: 32636299 BACKGROUND

MeSH Terms

Conditions

cyclopia sequence

Interventions

Minocycline

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Wouter Hoefsloot, MSc, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A single group, two-period, fixed-order pharmacokinetic study

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: May 16, 2023
• Study Start: May 8, 2023
• Primary Completion: May 14, 2025
• Study Completion: June 11, 2025
• Last Updated: June 29, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will become available for 15 years after the first study report has been published.
• Access Criteria: To be determined

Locations

NL (1)