The objective of this trial is to compare the total and regional deposition of aerosol in the lungs and oropharynx of patients with COPD at 3 different inspiratory flow rates following inhalation of Berodual® delivered via the Respimat® inhaler and Berodual® delivered via an HFA-metered dose inhaler.

Condition	Intervention	Phase
Pulmonary Disease, Chronic Obstructive Asthma	Device: Berodual HFA-MDI  Device: Berodual Respimat	Phase IV

Further Study Details: 

Primary Outcomes: Primary Endpoint: The primary endpoint is whole lung deposition.
Secondary Outcomes: Secondary Endpoint: The Respimat® inhaler will also be compared with the MDI in terms of o Central lung zone deposition o Intermediate lung zone deposition o Peripheral lung zone deposition o Ratio of peripheral to central zone deposition
Expected Total Enrollment:  18

This is a single dose, randomised, active-controlled, six period, open-label cross-over trial in adult patients with COPD.

Berodual® (fenoterol hydrobromide 50 µg + ipratropium bromide 20µg) will be delivered via the Respimat® inhaler and the MDI at 3 different inspiratory flow rates: 15 L/min, 30 L/min and 90 L/min. The optimal flow rate is expected to be 30 L/min for both inhalers.

On each test day patients will practise the inhalation manoeuvre with either a placebo Respimat® or MDI inhaler. When patients can perform the inhalation technique correctly and they can obtain the required inspiratory flow rates the placebo will be replaced with the radio-labelled formulation.

The primary analysis will be carried out using the Sign Test. This is a non-parametric analysis in which no assumptions are made about the shape of the distribution of the responses from the Respimat® inhaler and from the MDI under the null hypothesis.

Study Hypothesis:

The null hypothesis is that flow rate has the same effect on the Respimat® and MDI inhalers. The alternative hypothesis is that flow rate has a different effect on the Respimat® inhaler than on the MDI inhaler.

This means that under the null hypothesis the median of the differences between the Respimat® inhaler and MDI pairs is zero i.e. the differences are equally likely to be positive or negative. Under the alternative hypothesis the median of the differences between the Respimat® inhaler and MDI pairs is not zero i.e. the frequencies of the positive and negative signs are different.

Comparison(s):

For the primary comparison the whole lung deposition achieved for each patient at the 90 L/min flow rate will be expressed as a percentage of the whole lung deposition achieved by that patient at the 30 L/min flow rate for the Respimat® and MDI inhalers separately. The difference between each pair of observations ((Respimat® 90 L/min / Respimat® 30 L/min) - (MDI 90 L/min / MDI 30 L/min)) will then be calculated and the sign of the direction of the difference noted i.e. positive or negative.

The probability associated with the occurrence of the observed number of positive and negative differences will then be determined by reference to the binomial distribution with the probability of a positive or negative difference equal to 0.5 under the null hypothesis. If the alternative hypothesis is, however, true and flow rate does in fact have less effect on the Respimat® inhaler than on the MDI inhaler, then there is likely to be a statistically significant greater number of positive differences.

Ages Eligible for Study:  40 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

oCOPD patients FEV1 less or equal 65 % pre FEV1 less or equal 70 % of FVC

Exclusion Criteria Patients with any upper respiratory infection in the past 14 days prior to the Screening Visit (Visit 1) Patients with any unstable or life-threatening cardiac arrhythmia

Please refer to this study by ClinicalTrials.gov identifier  NCT00153075

Bettina Hederer, Dr.      +49 (6132) 77-3236  Ext. 3236    HEDERER@ing.boehringer-ingelheim.com

Germany
      Inamed Research GmbH & Co. KG, Gauting,  82131,  Germany

Study chairs or principal investigators

Bettina Hederer, Dr.,  Study Chair,  B.I. Pharma GmbH & Co. KG   

Study ID Numbers:  215.1364
Last Updated:  September 9, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00153075
Health Authority: Germany: Federal Institute for Drugs and Medicinal Devices; Germany: Bundesamt für Strahlenschutz
ClinicalTrials.gov processed this record on 2005-09-13