Argenta Discovery, a respiratory drug development company, presented data from a Phase II chronic obstructive pulmonary disease (COPD) trial at the European Respiratory Society meeting in Vienna.
The trial investigated the effect of ADC4022 (low-dose inhaled theophylline) in a co-administration study with inhaled budesonide.
Pre-clinical studies undertaken by Argenta indicated that ADC4022 and inhaled corticosteroids have little effect on lung inflammation when given separately, but are synergistic when given together.
The aim of the four-week Phase II study with ADC4022 was to assess whether the activity of inhaled corticosteroids in COPD - which are relatively ineffective when given alone - can be enhanced by the addition of ADC4022 and bring a meaningful improvement in the treatment of this condition.
The study showed that there was a significant beneficial treatment effect on lung function over the four-week period in COPD patients treated with ADC4022 and budesonide compared to those patients treated with placebo and budesonide.
Changes in the markers of inflammation in both sputum and biopsy were observed after the co-administration of ADC4022 and budesonide by the inhaled route.
Prof Neil Barnes, principal investigator for the study, said: 'These data are very encouraging, given the short treatment period and the relatively small number of subjects studied, and are supportive of an enhanced pharmacological effect for the inhaled combination therapy.
'If these findings can be confirmed in longer-term trials, they would also be expected to result in significant benefit for patients, including a reduction in the incidence and severity of exacerbations and an improvement in quality of life,' he added.
Dr Christopher Ashton, Argenta's chief executive officer, said: 'The development of a safe, well-tolerated and effective anti-inflammatory drug for COPD is one of the key goals for the pharmaceutical industry.
'This study emphasises the significant potential of an inhaled combination of low-dose theophylline with an inhaled corticosteroid to provide an effective therapy for COPD and steroid-resistant asthma.
'As part of our further development of this exciting approach, we are currently planning a follow-on three month dose-ranging study,' he added.
The study was conducted in patients with moderate-to-severe COPD.
Following a four-week pre-treatment period with nebulised budesonide (1mg twice daily), patients received either nebulised ADC4022 (12.5mg) or placebo twice daily in addition to budesonide for a further four weeks (n=91).
Data from the study demonstrated that, in the absence of long-acting bronchodilator therapy, there was a favourable treatment effect on pulmonary function in patients who received nebulised ADC4022 co-administered with budesonide, compared to patients who received placebo plus budesonide (treatment differences at four weeks for FEV1 and FVC were 142mL and 281mL respectively, p<0.05).
Consistent with this effect on lung function, 20 per cent less subjects required rescue medication (ipratropium) on ADC4022 treatment compared to placebo.
There were changes in inflammatory cell populations that were also indicative of a pharmacological effect of ADC4022 plus budesonide in the lung.
In the sputum, an increase in the percentage of sputum neutrophils (p=0.089) was observed that was associated with a concordant decrease in the percentage of macrophages in the ADC4022-plus-budesonide group compared to the placebo-plus-budesonide group.
In bronchial biopsies from a small cohort of patients (n=30), CD8+ T cells and CD68+ macrophages were reduced (p=0.141 and p=0.181 respectively), supporting the anti-inflammatory effect of ADC4022 when co-administered with budesonide.
There were no serious adverse events attributable to the co-administration of ADC4022 and budesonide.
The excellent tolerability for inhaled ADC4022 was reflected in the low systemic exposure of theophylline at concentrations that were at least 20-fold lower than those required for oral activity as a bronchodilator.
The clinical trial identifier was NCT00634413.
