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Sponsored by: |
Boehringer Ingelheim Pharmaceuticals |
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Information provided by: | Boehringer Ingelheim Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT00239421 |
This is a six-week, randomized, double-blind, quadruple-dummy parallel group multiple dose study comparing the efficacy and safety of tiotropium inhalation capsules (18 µg per day) plus formoterol inhalation capsules (12 µg twice daily) to salmeterol inhalation aerosol (50 µg b.i.d.) plus fluticasone inhalation aerosol (500 µg b.i.d.) in patients with chronic obstructive pulmonary disease (COPD). Diagnosis and main criteria for inclusion were the following: Outpatients of either sex, aged >= 40 years with a diagnosis of COPD (GOLD criteria); post-bronchodilator FEV1 < 80% predicted [ECSC criteria] and post-bronchodilator FEV1/FVC < 70% at Visit 1, pre-bronchodilator FEV1 <= 65% [ECSC criteria] at Visit 2, smoking history of > 10 pack-years, no history of asthma. Duration of treatment was 42 days.
Criteria for evaluation are the following: FEV1AUC(0-12) and peak FEV1 (obtained within the first three hours of testing) after six weeks, FEV1, FVC, PEFR, rescue medication use, adverse events, pulse rate, blood pressure, physical examination.
Statistical methods: Analysis of covariance with terms for treatment, pooled centre (country) and baseline reading. Descriptive statistics.
Condition | Intervention | Phase |
---|---|---|
Pulmonary Disease, Chronic Obstructive |
Drug: Test: Tiotropium 18 µg per day (one inhalation capsule) plus 12 µg formoterol twice daily (two times one
inhalation capsule) Drug: Reference: Salmeterol MDI 50 µg (2 puffs of 25 µg each) b.i.d., plus fluticasone propionate MDI 500 µg (2 puffs of 250 µg each) b.i.d. |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A Six-Week, Randomized, Double-Blind, Quadruple-Dummy Parallel Group Multiple Dose Study Comparing the Efficacy and Safety of Tiotropium Inhalation Capsules Plus Formoterol Inhalation Capsules to Salmeterol Inhalation Aerosol Plus Fluticasone Inhalation Aerosol in Patients With Chronic Obstructive P |
Estimated Enrollment: | 492 |
Study Start Date: | November 2003 |
Estimated Study Completion Date: | September 2004 |
Tiotropium (Spiriva®) is a once-daily inhaled anticholinergic for the treatment of COPD. A six-week, multicentre, randomized, double-blind, parallel group study was conducted to compare the efficacy and safety of the free combination of tiotropium 18 µg once daily plus formoterol 12 µg b.i.d. [Tio+For] to salmeterol 50 µg b.i.d. plus fluticasone 500 µg b.i.d. [Sal+Flu] in COPD patients. Information regarding the differential efficacy and safety of the two different combinations may be essential for physicians to make informed choices of therapy for COPD patients considered candidates for combination therapy. Following an initial screening visit, subjects entered a two or four-week run-in period in which they received ipratropium (Atrovent®) on a regular basis. At the second visit (Baseline), subjects were randomized into the six-week, double blind portion of the study in which they received either Tio+For or Sal+Flu. After three weeks of treatment, an interim visit was scheduled. After six weeks of treatment, a 12-hour profile of pulmonary function testings (FEV1, FVC) was obtained. Spirometric measurements were performed at pre-dose and 30 minutes,
1, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing. There were two co-primary endpoints: FEV1 area under the curve for the time period 0 to 12 hours (FEV1 AUC0-12) and peak FEV1. The efficacy evaluation (intention-to-treat) comprised 592 patients [Tio+For: N=297, Sal+Flu: N=295]. The two treatment groups were comparable with regard to demographic data and baseline disease characteristics [Baseline FEV1 (±SE): Tio+For: 1.310 L (±0.026 L); Sal+Flu: 1.325 L (±0.025 L)]. Adjustment was done for baseline and centre-effects.
Study Hypothesis:
The following primary hypotheses (one-sided) were tested with regard to superiority (all means are adjusted means): H01: FEV1AUC(0-12 hours) (tiotropium+formoterol) <= FEV1AUC (0-12 hours) (salmeterol+fluticasone) versus H11: FEV1AUC(0-12 hours) (tiotropium+formoterol) > FEV1AUC 0-12 hours(salmeterol+fluticasone)
It was stipulated in the protocol that, if the null hypothesis H01 was rejected in favour of H11, then the following hypothesis would be tested: H01: Peak FEV1 (tiotropium+formoterol) <= Peak FEV1 (salmeterol+fluticasone) versus H11: Peak FEV1 (tiotropium+formoterol) > Peak FEV1 (salmeterol+fluticasone)
Each step was only considered confirmatory providing all previous steps were successful. If any of the previous steps were not successful, any analysis of the current step would have been considered descriptive.
Comparison(s):
Test therapy:
Test product: Tiotropium inhalation capsules plus formoterol inhalation capsules Dose: 18 µg tiotropium per day (one capsule), 12 µg formoterol twice daily (two times one capsule) Mode of administration: inhalation via the Handihaler device (tiotropium), inhalation via the Blue Inhaler device (formoterol)
Reference therapy:
Test product: Salmeterol plus fluticasone propionate Dose: Salmeterol 50 µg (2 puffs of 25 µg each) b.i.d., fluticasone propionate 500 µg (2 puffs of 250 µg each) b.i.d. Mode of administration: inhalation via MDI
The treatment duration was 42 days each. Primary endpoint measurements were performed on the last treatment day.
Ages Eligible for Study: | 40 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
1.
21. Patients who have been treated with inhaled steroids within two months prior to Visit 1, including combinations of inhaled steroids and long-acting beta-adrenergics.
22. Patients with known hypersensitivity to anticholinergic drugs, beta adrenergics, lactose or any other components of the inhalation capsule delivery system or any other components of the aerosol delivery systems.
23. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for the previous three months.
24. Patients with any respiratory infections in the six weeks prior to the Screening Visit (Visit 1) or during the run-in period.
25. Patients who are currently participating in another study.
26. Patients requiring more than eight puffs of salbutamol on three or more consecutive days during the run-in period.
Study Chair: | Boehringer Ingelheim Study Coordinator | B.I. Pharma GmbH & Co. KG |
Study ID Numbers: | 205.287 |
Study First Received: | October 14, 2005 |
Last Updated: | July 6, 2009 |
ClinicalTrials.gov Identifier: | NCT00239421 History of Changes |
Health Authority: | Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM); Austria: Federal Ministry for Health and Women; Belgium: Institutional Review Board; Denmark: Danish Medicines Agency; France: Afssaps - French Health Products Safety Agency; Netherlands: The Central Committee on Research Involving Human Subjects (CCMO); South Africa: Medicines Control Council |
Anti-Inflammatory Agents Neurotransmitter Agents Salmeterol Cholinergic Antagonists Adrenergic Agents Adrenergic beta-Agonists Respiration Disorders Anti-Asthmatic Agents Anti-Allergic Agents Cholinergic Agents Adrenergic Agonists |
Lung Diseases, Obstructive Respiratory Tract Diseases Lung Diseases Fluticasone Formoterol Chronic Disease Peripheral Nervous System Agents Tiotropium Bronchodilator Agents Pulmonary Disease, Chronic Obstructive |
Anti-Inflammatory Agents Parasympatholytics Respiratory System Agents Disease Attributes Neurotransmitter Agents Cholinergic Antagonists Adrenergic Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Cholinergic Agents Adrenergic Agonists Lung Diseases, Obstructive Pathologic Processes Respiratory Tract Diseases Therapeutic Uses |
Fluticasone Formoterol Tiotropium Dermatologic Agents Salmeterol Adrenergic beta-Agonists Respiration Disorders Anti-Asthmatic Agents Anti-Allergic Agents Pharmacologic Actions Autonomic Agents Lung Diseases Chronic Disease Peripheral Nervous System Agents Bronchodilator Agents |