Inhalation of Moli1901 in patients with cystic fibrosis.
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 FEV(1) developed following inhalation, which resolved spontaneously, and in a second patient in whom transient throat numbness developed during drug inhalation. A significant improvement of FEV(1) 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.
Grasemann
Hartmut
H
The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada. hartmut.grasemann@sickkids.ca
Stehling
Florian
F
Brunar
Helmut
H
Widmann
Rudolf
R
Laliberte
Terry W
TW
Molina
Luis
L
Döring
Gerd
G
Ratjen
Felix
F
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020545:Respiratory Mucosa / Q000502:physiology
D018118:Chloride Channels; C477246:Moli1901; D010456:Peptides, Cyclic; D019005:Cystic Fibrosis Transmembrane Conductance Regulator