NEW YORK (Reuters Health) – A Phase III trial found that inhaled mannitol helped decrease respiratory symptoms in patients with cystic fibrosis.

In the study, published in the European Respiratory Journal, patients experienced a “clinically meaningful” improvement in airway function, regardless of whether or not they were also being treated with rhDNase.

Dr. Diana Bilton of Royal Brompton Hospital in London and colleagues note that the treatment is convenient and only takes a few minutes, and so might be ideal for young CF patients who may have difficulty with treatment adherence.

The trial involved 324 subjects in Australia, New Zealand, Ireland and the UK who were an average of 23 years old. Patients were randomized 3:2 to receive mannitol, a sugar alcohol (twice daily at 400 mg) or the control, which was a 50 mg subtherapeutic dose of mannitol.

All patients took a dose of the short acting bronchodilator salbutamol (400ug) between 5 and 15 minutes before taking each dose of the treatment medication.

The double-blind trial lasted 26 weeks, and was followed by a 26-week open label extension.

A total of 177 patients taking mannitol and 118 in the control group received at least one medication dose and were included in the intention to treat analysis.

By 6 weeks into the trial, an improvement in the primary endpoint, change in forced expiratory volume (FEV1), was already seen in the mannitol group compared to the control.

By the end of the double-blind phase, patients taking therapeutic mannitol had a 118.9 mL (6.5%) improvement in FEV1, compared to 26.0 mL (2.4%) in control patients.

Similar improvements were seen in patients who were and were not also being treated with rhDNase.

At 26 weeks, the odds of a clinically meaningful response were almost twice as high in patients taking mannitol as in controls, and there was a trend towards improvement in pulmonary exacerbation and respiratory, vitality, and physical domain scores in the intervention group.

The authors noted that during the open label phase of the study, control patients who began taking mannitol also showed a clinically and statistically significant improvement in FEV1. Patients who were initially randomized to mannitol maintained their increases in FEV1 during the 26-week extension.

Rates of adverse and serious adverse events were similar in the two groups, but treatment-related adverse events were more common in the mannitol group (40.7%) than in the control group (22%). The most common mannitol-related adverse events were cough, haemoptysis, and pharygolaryngeal pain.

However, Dr. Bilton and her colleagues said the drug was well tolerated.

They added that each of dose mannitol only took 2 to 5 minutes to administer, and that most patients who completed the double-blind trial on mannitol chose to continue taking it during the open-label phase of the study.

And the authors concluded that “inhaled mannitol appears to have an acceptable safety profile for patients with CF, and demonstrates that mannitol treatment, over and above existing standard care provides both early and sustained clinically meaningful improvements in airway function, irrespective of concomitant rhDNase use, in a representative population of cystic fibrosis subjects.”

European Respiratory Journal.