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: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Neupharma Srl
• Collaborators: Aptuit Srl; Centro Ricerche Cliniche di Verona; Pari Pharma GmbH; Sintesi Research Srl
• Treatments: Teicoplanin

Criteria

INCLUSION CRITERIA:

1. Male or female patients, aged ≥18 years with a confirmed diagnosis of cystic fibrosis.

2. Patients with body weight ≥50 kg and ≤100 kg

3. Patients with body mass index (BMI) between 18.0 and 30 kg/m2.

4. Patients with FEV1 > 50% of predicted.

5. Patients with regular mucus production due to cystic fibrosis.

6. Patients who are able to understand the nature of the study and willing to comply with the protocol requirements.

7. Patients who have signed written informed consent to participate to the study after risks have been fully explained.

EXCLUSION CRITERIA:

1. Patients treated with nebulized antibiotics within 14 days or mucolytic agents, hypertonic saline solution within 48 hours before administration of the Investigational Product or during the study.

2. Patients with medical history of hemoptysis (> 300 cc in 30 days).

3. Patients with decreased liver function (AST or ALT > 3 times higher in comparison to reference values).

4. Patients with eGFR < 60 mL/min/1.73 m2

5. Patients on the waiting list for lung transplantation.

6. Patients with known or suspected allergy or hypersensitivity to glycopeptides.

7. Patients treated with Teicoplanin for inhalation and systemic within 4 weeks before each dosing occasion.

8. Patients with known episodes of bronchoconstriction after drug inhalation.

9. Patients who are participating or have participated in other clinical studies within the 30 days before the study enrolment.

10. Female patients who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical study and for one months later.

11. Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception. * * Methods at low risk of contraceptive failure (less than 1% per year) when used consistently, including: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), some intra-uterine devices, abstinence or vasectomized partner. Contraception should be maintained until 1 month after the last visit.