A Randomised, Double-blind, Double-dummy, Crossover Efficacy and Safety Comparison of 6-week Treatment Periods of the Free Combination of Tiotropium Inhalation Powder Capsule (18 μg) + Formoterol Inhalation Powder Capsule (12 μg) QD, Tiotropium Inhalation Powder Capsule (18 μg) QD and Formoterol Inhalation Powder Capsule (12 μg) BID in Patients With COPD

Boehringer Ingelheim0 sites74 target enrollmentFebruary 2002

ConditionsPulmonary Disease, Chronic Obstructive

InterventionsTiotropium + formoterol combination Tiotropium Formoterol

DrugsTiotropium + formoterol combination Tiotropium Formoterol

Overview

Phase: Phase 2
Intervention: Tiotropium + formoterol combination
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: Boehringer Ingelheim
Enrollment: 74
Primary Endpoint: Change in area under the curve from pre-dose to 12 hours of the forced expiratory volume in one second (FEV1 AUC0-12h)
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

Study to evaluate the lung function response to the free once-daily combination of tiotropium + formoterol compared to formoterol BID and tiotropium QD

Registry

clinicaltrials.gov

Start Date

February 2002

End Date

August 2002

Last Updated

11 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•All patients had to sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which included medication washout and restrictions
•All patients had to have a diagnosis of chronic obstructive pulmonary disease and had to meet the following spirometric criteria:
•Patients had to have relatively stable moderate to severe airway obstruction with an FEV1 ≤ 60% of predicted normal and FEV1 ≤ 70% of FVC (Visits 1 and 2)
•Male or female patients 40 years of age or older
•Patients had to be current or ex-smokers with a smoking history of more than 10 pack-years (Patients who had never smoked cigarettes had to be excluded)
•Patients had to be able to perform technically acceptable pulmonary function tests and had to be able to maintain records (Patient Daily Diary Record) during the study period as required in the protocol
•Patients had to be able to inhale medication in a competent manner from the HandiHaler® device, the Blue Inhaler device and from a metered dose inhaler (MDI)

Exclusion Criteria

•Patients with significant diseases other than COPD had to be excluded. A significant disease was defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
•Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis if the abnormality defined a disease listed as an exclusion criterion
•All patients with an serum glutamate oxaloacetate transaminase (SGOT) \> 80 IU/L, serum glutamate pyruvate transaminase (SGPT) \> 80 IU/L, bilirubin \> 17 μmol/L or creatinine \> 110 μmol/L (males) / 95 μmol/L (females) had to be excluded regardless of clinical condition
•Patients with a recent history (i.e., six months or less) of myocardial infarction
•Patients with any cardiac arrhythmia requiring drug therapy or who had been hospitalised for heart failure within the past three years
•Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma were allowed
•Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction.
•Patients with prostatic hypertrophy controlled by medication were allowed
•Patients with known narrow-angle glaucoma
•Patients with a history of asthma, allergic rhinitis or who had a total blood eosinophil count ≥600 mm3

Arms & Interventions

tiotropium + formoterol

Intervention: Tiotropium + formoterol combination

tiotropium

Intervention: Tiotropium

formoterol

Intervention: Formoterol

Outcomes

Primary Outcomes

Change in area under the curve from pre-dose to 12 hours of the forced expiratory volume in one second (FEV1 AUC0-12h)

Time Frame: after 6 weeks of each treatment

Change in FEV1 AUC0-24h

Time Frame: after 6 weeks of each treatment

Secondary Outcomes

Change in FEV1 AUC12-24h(after 6 weeks of each treatment)
Change in AUC of the forced vital capacity (FVC AUC0-12h)(after 6 weeks of each treatment)
Change in FVC AUC0-24h(after 6 weeks of each treatment)
Change in FVC AUC12-24h(after 6 weeks of each treatment)
Change in peak FEV1 response(after 6 weeks of each treatment)
Change in trough FEV1 response(after 6 weeks of each treatment)
Change in peak FVC response(after 6 weeks of each treatment)
Change in trough FVC response(after 6 weeks of each treatment)
Individual FEV1measurements at each time point(up to 6 weeks)
Individual FVCmeasurements at each time point(up to 6 weeks)
Peak expiratory flow rate (PEFR)(weeks 4 to 6 of each treatment period)
Number of inhalations of rescue salbutamol therapy used per day(weeks 4 to 6 of each treatment period)
Assessment of daytime COPD symptom score rated on a 6-point rating scale(weeks 4 to 6 of each treatment period)
Assessment of nighttime COPD symptom score rated on a 5-point rating scale(weeks 4 to 6 of each treatment period)
Number of patients with adverse events(up to 23 weeks)