Approved ciclesonide effectively reaches the small airways in the lungs of asthma patients where it is needed, whether or not a spacer (a device to aid the patient in delivering medication from a metered-dose inhaler to the lungs) is used.

High lung deposition is a desirable characteristic for an inhaled corticosteroid with targeted therapeutic activity. The higher the lung deposition, the more of the drug reaches its target in the airways and the lungs. In the case of ciclesonide, it is primarily “activated” in the lung to exert its therapeutic effect. This leaves a relatively small inactive amount of the drug remaining in the oropharynx.

In a study conducted by Dr. Stephen Newman, the deposition of ciclesonide in the lungs, oropharynx, oesophagus and stomach was analyzed after 12 adult asthma patients inhaled a single dose of 320µg of radiolabeled ciclesonide via metered-dose inhaler. Fifty-two percent (52%) of the dose was deposited in the lung with over half of that amount deposited in the target small airways in the periphery of the lungs. A second, related study showed no difference in the pharmacokinetics of the activated drug measured in the serum after 30 asthma patients received a single 320µg dose of ciclesonide either directly from a metered-dose inhaler or using a spacer. This indicates that ciclesonide has similar lung deposition with and without a spacer.

Taken together, these studies add information about how ciclesonide is distributed in the body. The drug is delivered to the small airways of the lung where the inflammation is, independent of use of a spacer. While many patients across the age spectrum master the skill of using a metered-dose inhaler, with or without a spacer, some continue to have difficulty. Ciclesonide is effectively delivered either way.

Trial Designs and Results

2D gamma-scintigraphy and 3D single photon emission computed tomography imaging was used to determine the portion of a single 320µg dose of radiolabeled ciclesonide inhaled by patients with mild asthma. The mean percentage of the ciclesonide dose was highest in the lung (52 percent), with 56 percent of that amount reaching the small airways in the periphery of the lungs. Less ciclesonide was detected in other organs including the oropharynx (33 percent), oesophagus (6 percent) and stomach (5 percent). An exhaled air filter captured 4 percent of the dose.

The second study was a randomized, open-label, two-period crossover study which compared the pharmacokinetics of the active ciclesonide metabolite (which is formed through bioactivation of ciclesonide by esterases in the lungs) when ciclesonide was dosed with or without a spacer. Pharmacokinetic analysis served as a measure of pulmonary deposition and absorption. All measured pharmacokinetic characteristics (area under the serum concentration time curve, maximum concentration in serum and elimination half-life) were comparable, suggesting that a spacer is generally not required, nevertheless some patients may benefit from such a device.

About Asthma

Asthma is a chronic lung disease caused by airway inflammation and results in airway constriction in response to certain stimuli. It is characterized by a variety of symptoms including wheezing, coughing and a tightening of the airways, which causes shortness of breath and can be life-threatening. According to the Global Initiative for Asthma (GINA), more than 300 million people worldwide suffer from asthma. The prevalence of asthma is increasing by approximately 50 percent every decade and worldwide deaths from asthma total more than 180,000 annually.

About Ciclesonide

Ciclesonide 160µg has a UK marketing authorization for the management of persistent asthma in patients 18 years of age and older. Ciclesonide is an inhaled corticosteroid with novel release and distribution properties resulting in lung-targeted anti-inflammatory effects. Inhaled corticosteroids, considered to be the foundation of asthma treatment, work by reducing inflammation – the underlying disease process – in the lungs and airways. In clinical trials, ciclesonide was shown to improve lung function, asthma symptoms, and reduce the need for medications necessary to treat acute asthma attacks. The most frequently reported adverse events seen in ciclesonide clinical trials were nasopharyngitis, headache and upper respiratory tract infection. Ciclesonide was approved in Australia and the United Kingdom this year, and has been submitted for approval in other countries around the world. Additionally, ALTANA’s US partner, Aventis, applied to the FDA for approval of the asthma drug ciclesonide at the end of 2003. Teijin, ALTANA’s partner in Japan, submitted an application for approval for ciclesonide in January 2004. Ciclesonide is not yet available for prescription.