Open-label, Dose-escalation Study to Evaluate the Pharmacokinetics of Inhaled Teicoplanin in Cystic Fibrosis Patients
Status:
Completed
Trial end date:
2020-09-30
Target enrollment:
Participant gender:
Summary
Cystic Fibrosis (CF) is the most common autosomal recessive lethal disorders affecting
1:2.500 newborns among Caucasians. CF patients are peculiarly susceptible to infection and
colonization of the respiratory tract with pathogens. In particular, Methicillin-resistant
Staphylococcus aureus (MRSA) has become the third most prevalent bacterium in CF in the U.S.
and has been increasing in other countries. Apart from the difficulty of treating the
infection because of its antimicrobial resistances, MRSA is transmissible between individuals
with and without CF. Chronic MRSA infection is associated with worse outcomes, and
treatment/eradication is challenging. Antibiotic dosing and choices should be optimized to
minimize further resistance and to maximize chances of successful therapy. Yet, MRSA has
several mechanisms to escape clearance by the immune system and antibiotic killing. For these
reasons, a better understanding of preventive measures and early therapy is of key
importance. In consideration of all these assessments there is an emerging consensus that
MRSA is an important pathogen in CF rather than simply a marker of severe disease. However,
to date there are no guidelines or recommendations on the choice of antibiotics for MRSA in
CF. Glycopeptides are an important class of antibiotics active against Gram-positive
pathogens. These include teicoplanin and vancomycin, which are currently in widespread use
and are active against MRSA. Teicoplanin is often preferred to vancomycin for intravenous
treatment because of its better safety profile but its use in MRSA lung infection is limited
by its limited lung penetration. Teicoplanin is mainly used for injection/infusion.
Inhalation of anti-microbial drugs is a cornerstone in the treatment of patients with CF,
since inhaled antibiotics decrease the rate of decline of lung function, improve the quality
of life, and reduce the frequency of exacerbations and hospital admissions. It is expected
that, using inhalation route, efficacy would be improved and risk of resistance reduced. At
present, no antibiotic active against MRSA is available as an inhaled formulation. The
objective of this phase I, first-in-man clinical study is to identify the dose providing,
after single inhalation administration, a sputum Teicoplanin concentrations exceeding the
drug concentration required to inhibit bacterial growth for at least 8 hours, while
minimizing the development of resistance.
Phase:
Phase 1
Details
Lead Sponsor:
Neupharma Srl
Collaborators:
Aptuit Srl Centro Ricerche Cliniche di Verona Pari Pharma GmbH Sintesi Research Srl