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Pharmacokinetic Study With a Loading Dose of Clofazimine in Adult Patients With Nontuberculous Mycobacterial Disease

NCT05294146 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 12

Last updated 2023-08-16

No results posted yet for this study

Summary

Clofazimine (CFZ) is a promising drug for the treatment of NTM diseases. CFZ is highly active in vitro against M. abscessus and M. avium, the most common NTM pathogens, and shows synergy with macrolides and amikacin. The results from limited clinical studies with CFZ-based treatment regimens are promising. CFZ is currently considered an alternative drug for patients with M. avium complex infections, who are intolerant of first-line drugs. CFZ is a first-line oral drug for treatment of M. abscessus infections.

CFZ might prove to be a cornerstone in NTM treatment, but its optimal dosage is not known. The current dose for adults is 100 mg oncedaily. However, due to the complex pharmacokinetics (PK) of CFZ - it is highly protein bound, extremely lipophilic and accumulates in fatty tissues resulting in a long elimination half-life of \~30 days - it takes several months before steady state, and presumably effective, concentrations are achieved. With the use of a loading dose regimen concentrations similar to those at steady state could be reached faster, possibly leading to improved early treatment efficacy.

The overarching aim of this study is to contribute to dose optimization of CFZ in the treatment of NTM diseases. It will be an explorative, single-center, one-arm, open label, pharmacokinetic study. A number of 10 patients with pulmonary or extrapulmonary NTM disease will be included. Patients will receive a loading dose regimen of 300 mg once daily for 4 weeks and will then continue with a standard dose of 100 mg once daily until a total 4 months of treatment with CFZ.

The primary objective of this study is to describe the PK of CFZ, after 4 weeks of treatment with a loading dose regimen of 300 mg once daily, in adult patients with pulmonary or extrapulmonary NTM disease

Conditions

  • Nontuberculous Mycobacterial Diseases

Interventions

DRUG

Clofazimine

All participants will receive an (experimental) oral loading dose regimen of 300 mg clofazimine once daily (= 3 capsules of 100 mg) for 4 weeks. Afterwards, all participants will continue with a standard oral dose of 100 mg clofazimine once daily (= 1 capsule of 100 mg) until a total 4 months of treatment with CFZ. Blood samples will be taken at Day 28 (+/- 2 days), Day 29 (Day 28 +1) and after 4 months of treatment to assess the pharmacokinetics of CFZ, both with the loading dose and the standard dose. In addition, the safety/tolerability of CFZ will monitored.

Sponsors & Collaborators

  • Radboud University Medical Center

    lead OTHER

Principal Investigators

  • Prof. dr. R.E. Aarnoutse, PharmD, PhD · Radboud University Medical Center

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SEQUENTIAL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-02-14
Primary Completion
2023-05-01
Completion
2023-08-08

Countries

  • Netherlands

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05294146 on ClinicalTrials.gov