Date: 2015-12-16
Type of
information: Results
phase: 2
Announcement: results
Company: Pharmaxis (Australia)
Product: Bronchitol® (mannitol)
Action
mechanism: Bronchitol® is a precision spray-dried form of mannitol, delivered to the lungs by a specially designed, portable inhaler.
Disease: cystic fibrosis
Therapeutic
area: Rare diseases - Genetic diseases
Country: Belgium, Canada, France, Germany, Italy, Netherlands, Switzerland, UK
Trial
details: The DPM-CF-204 trial is a multicentre, randomised, double-blind, crossover, placebo-controlled study determining the efficacy of dry powder mannitol in improving lung function in subjects with cystic fibrosis aged six to seventeen years. (NCT01883531)
Latest
news:
- • On December 16, 2015, Pharmaxis announced positive results of its recently completed Phase II trial of Bronchitol® (mannitol) in children and adolescents with cystic fibrosis (CF). The trial, conducted across 39 global centres, met its primary endpoint and confirms that Bronchito®l is efficacious in young patients, regardless of concomitant dornase alfa use.
- The trial was conducted in centres in Belgium, Canada, France, Germany, Italy, Netherlands, Switzerland, and the United Kingdom. It was designed in consultation with the EMEA as a condition of the marketing authorisation granted for Bronchitol for treating adult cystic fibrosis patients in Europe. To meet the condition in full Pharmaxis will submit a detailed study report to the EMEA in 2016. Based on the positive trial results Pharmaxis will consider an application to extend the European Union marketing authorisation to include children and adolescents but it is not yet known if the trial results alone will be sufficient to gain an approval.
The trial (CF204) was a crossover design with patients aged 6 to 17 years receiving either 400mg of Bronchitol or a placebo twice a day for eight weeks on top of standard of care before a washout period of eight weeks followed by a further eight week treatment period on the alternate treatment. During the Bronchitol treatment period patients had a statistically significant improvement in lung function compared to placebo showing an absolute improvement of 3.42% (p=0.004) in FEV1 (% predicted) which equates to a relative change in FEV1 (% predicted) of 4.97% (p=0.005). This treatment improvement in the primary endpoint occurred irrespective of whether patients were taking dornase alfa.
Secondary endpoints in the trial included absolute change in FEF25-75 (% predicted) which is thought to have particular significance in younger patients. Bronchitol produced an absolute improvement of 5.75% (p=0.005) in FEF25-75 equating to a relative improvement of 10.5%. In other secondary endpoints, treatment induced sputum weight was significantly increased (p=0.012) and a positive trend was seen in FVC. Although not recorded as an endpoint, patients on Bronchitol experienced approximately 25% fewer lung infections and exacerbations of CF which is supportive of the improvements seen in earlier studies despite the short duration of this study.
The 92 subjects randomized and treated had a mean age of 12 years. The mean lung function on entry to the trial was 72.2% of the predicted normal FEV1, and 60% of the population were female. 69% of the patients were taking dornase alfa and 70% were on antibiotics.
In the trial subjects, Bronchitol was well-tolerated overall and had a favourable safety profile. There was no difference in the rate of adverse events or serious adverse events between the treatment groups. The most common adverse event was cough, which was mild to moderate in most cases and similar between the treatment arms. Three patients experienced haemoptysis on Bronchitol and two on placebo. All haemoptysis events were categorised as either scant or mild and the overall level is below background rates reported in other comparable studies.
- The first scientific presentation of the results will be made at the European Cystic Fibrosis Society meeting in Switzerland in June 2016.
Is
general: Yes
