Chest
Original Research: Cystic FibrosisInhalation of Moli1901 in Patients With Cystic Fibrosis
Section snippets
Study Design
The study (Moli1901–008) was designed as a phase II, placebo-controlled, double-blinded, single center, multiple, rising-dose study. The study was approved by the Institutional Review Board of the University of Duisburg-Essen, Germany. Written informed consent was obtained from each CF patient and/or their parents.
Inclusion and Exclusion Criteria
Patients were eligible for participation if they were ≥ 16 years of age, had a confirmed diagnosis of CF (ie, positive sweat chloride value of ≥ 60 mEq/L and/or two identified CFTR
Demographic and Baseline Characteristics
The majority of CF patients were CFTR ΔF508 homozygous (n = 14), compound heterozygous (n = 6), or ΔF508/unknown (n = 3). Demographics and baseline characteristics of the study groups are given in Table 1. The median screening FEV1 was 90% predicted (range, 58 to 121% predicted). A nonsignificant tendency toward lower values in the group receiving a dose of 1.5 mg/d was observed (p = 0.2). Significant differences were seen for screening pulse oximetry (median, 96.5%; range, 95 to 100%; p =
Discussion
The inhalation of nebulized Moli1901 was well-tolerated by the CF patients included in this phase II trial. Although a transient significant decrease in FEV1 following the inhalation of Moli1901 occurred in one patient in the 1.5 mg/d treatment group, this resolved spontaneously. While this study was not primarily powered to assess efficacy, the present data additionally suggest that inhaled Moli1901 may result in a dose-dependent increase in pulmonary function in patients with CF.
The
Acknowledgment
The authors wish to acknowledge the valuable support of this study by Christine Bauer, Manuela Groch, and Dr. Peter Tinschmann.
References (19)
- et al.
Cystic fibrosis
Lancet
(2003) - et al.
A phase I trial of intranasal Moli1901 for cystic fibrosis
Chest
(2004) - et al.
Determination of the tissue distribution and excretion by accelerator mass spectrometry of the nonadecapeptide 14C-Moli1901 in beagle dogs after intratracheal instillation
Chem Biol Interact
(2005) - et al.
Extracellular ATP and UTP induce chloride secretion in nasal epithelia of cystic fibrosis patients and normal subjectsin vivo.
Chest
(1992) - et al.
Interaction of duramycin with artificial and natural membranes
Biochemistry
(1985) - et al.
Duramycin enhances chloride secretion in airway epithelium
Am J Physiol
(1990) - et al.
Duramycin increases intracellular calcium in airway epithelium
Membr Biochem
(1993) - et al.
Method of treating retained pulmonary secretions
US patent 5 512 269
(1996) - et al.
Bioelectric and fluid transport effects of the nonadecapeptide 2622U90 (duramycin) in normal human cystic fibrosis airway epithelium and canine airways [abstract]
Pediatr Pulm
(1998)
Cited by (0)
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).
This work was performed at the Children's Hospital, University of Duisburg-Essen, Essen, Germany.
Drs. Grasemann, Stehling, and Ratjen have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Dr. Molina is the founder and Chief Executive Officer of Lantibio Inc and holds equity in the company. Ms. Laliberte is a member of the management team of Lantibio Inc and holds equity in the company. Dr. Widmann is founder and Chief Executive Officer of AOP Orphan Pharmaceuticals AG, and holds equity in the company; Dr. Brunar is employed with AOP Orphan Pharmeceuticals AG. Consequently, both have a financial interest in the subject matter. Dr. Döring has received consultancy fees from AOP Orphan Pharmaceuticals AG.