Chest
Volume 131, Issue 5, May 2007, Pages 1461-1466
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Original Research: Cystic Fibrosis
Inhalation of Moli1901 in Patients With Cystic Fibrosis

https://doi.org/10.1378/chest.06-2085Get rights and content

Background

In cystic fibrosis (CF) patients, the absence or dysfunction of the chloride channel CF transmembrane conductance regulator (CFTR) results in reduced chloride ion transport in respiratory epithelial cells. Moli1901 stimulates an alternative chloride channel and may thus compensate for the CFTR deficiency in the airway epithelium of CF patients.

Methods

A phase II, placebo-controlled, double-blinded, single-center, multiple (5 consecutive days), rising-dose (daily dose, 0.5, 1.5, or 2.5 mg of Moli1901) study was conducted to investigate the safety and tolerability of multiple doses of aerosolized inhaled Moli1901 in 24 patients with CF and stable lung disease.

Results

Moli1901 was well tolerated in all but one CF patient, in whom a transient significant decrease in FEV1 developed following inhalation, which resolved spontaneously, and in a second patient in whom transient throat numbness developed during drug inhalation. A significant improvement of FEV1 was observed in the group receiving treatment with 2.5 mg/d Moli1901 compared to the group receiving placebo (p = 0.01 [Wilcoxon test]). Moli1901 was not detected in the plasma of the highest dose group.

Conclusions

The inhalation of Moli1901 up to a total cumulative dose of 12.5 mg appears to be safe in adult patients with CF. In addition, Moli1901 had a sustained beneficial effect on pulmonary function, which supports further studies of its efficacy in CF patients.

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)

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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.

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