12-Week Tiotropium 18?g q.d. in Patients With COPD and a Concomitant Diagnosis of Asthma for Safety and Efficacy

Condition(s) targeted: Pulmonary Disease, Chronic Obstructive; Asthma

Intervention: Tiotropium inhalation capsules (Drug); Placebo inhalation capsules (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Boehringer Ingelheim Pharmaceuticals

Official(s) and/or principal investigator(s):
Boehringer Ingelheim Study Coordinator, Study Chair, Affiliation: B.I. Pharma GmbH & Co. KG

The primary objective of this study is to demonstrate the superiority of tiotropium compared to plac ebo in the treatment of patients with COPD and a concomitant diagnosis of asthma

Official title: A 12-Week Randomized, Double Blind, Placebo Controlled, Parallel Group Trial Evaluating the Safety and Efficacy of Tiotropium 18 ?g qd in Patients With COPD and a Pre-Existing Diagnosis of Asthma

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: The primary efficacy endpoint is defined as area under the curve of change in FEV1 from baseline at visit 2 (day 1) for the time period from pre-dose to 6 hours post dose (AUC(0-6hours)FEV1) after 12 weeks of randomised treatment on visit 4 (day 85).

Secondary outcome: Secondary endpoints include additional FEV1 and FVC endpoints, morning and evening exspiratory flow rate (PEFR), number of puffs of rescue medication (salbutamol), adverse events, pulse rate, systolic and diastolic blood pressure

Detailed description: The objective of this trial is to evaluate the efficacy and safety of tiotropium in a subgroup of pa tients with COPD and pre-existing (concomitant) diagnosis of asthma. This is a 12-week, multi-centre

, multi-national, prospective, randomised, placebo controlled clinical trial. Following an initial s creening at Visit 1, all patients enter a two-week screening period. Patients pretreated with commer cially available Spiriva? have to be switched to ipratropium MDI q. i.d. four weeks before Visit 1. A t Visit 1, reversibility testing will be performed to determine eligibility. Patients who meet all inclusion and exclusion criteria will be randomised into the 12 week, double b lind portion of the study in which they will receive either tiotropium or placebo powder capsules to be inhaled via HandiHaler? once daily in the morning. In addition, patients are allowed to continue LABAs and steroids as concomitant medication. Salbutamol (100?g per puff) will be provided as rescu e medication. Patients have to record daily rescue salbutamol use on the Patient Daily Diary Card.

Pulmonary function testing will be conducted at - 30 and -10 minutes prior to administration

of study drug and thereafter at 30, 60 minutes and 2, 3, 4 and 6 hours post-dosing at visit 2 (day 1), visit 3 (day 29) and day 4 (day 85). Blood samples for laboratory testing will be collected at visit 1. Adverse events will be tracked th roughout the entire screening period and 12-week treatment period

Study Hypothesis:

The objective of this study, demonstrating the superiority of 18 ?g tiotropium c ompared to placebo in the treatment of patients with COPD and a concomitant diag nosis of asthma can be

tested using the hypotheses given below. H0: delta(T) - delta(P) = 0 versus HA: delta(T) -

delta(P) not equal to 0 where delta(T) and delta(P) represent the overall mean for the primary endpoint for tiotropium (T) and placebo (P), respectively. Testing of the null hypothesis will be performed using a 2 sided test of significance at an alpha level (type I error rate) of 0. 05.

Comparison(s):

Efficacy and Safety of tiotropium inhalation capsules is compared with placebo

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion criteria:

Diagnosis of COPD and diagnosis of asthma before the age of 30 Current or ex-smokers with a cigarette smoking history of at least 10 pack-years Treatment with inhaled steroids at least 1 year before study entry FEV1 increase of more than 12% 30 min. after 400 mcg salbutamol or documented re sersibility of 12% documented during the past 5 years FEV1 increase of more than 200 mL 30 min. after 400 mcg salbutamol or documented increase of 200 mL after reversibility test within the last 5 years Post bronchodilator FEV1 less than 80% predicted normal (ECCS) at visit 1 Post bronchodilator FEV1 less than 70% of FVC at visit 1

Exclusion criteria:

Respiratory infection or exacerbation 6 weeks prior to Visit 1 or during run-in period. Significant diseases other than COPD or asthma Myocardial infarction within the last 6 months Unstable or life-threatening cardiac arrhythmia requiring intervention or change in therapy in the last year Hospitalisation for heart failure (NYHA Class III or IV) within the last year History of life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis Known active tuberculosis History of thoracotomy with pulmonary resection History of cancer within the last 5 years (excluding treated basal cell carcinom

a) Patients requiring oxygen therapy for more than 1 hour per day Patients currently in a pulmonary rehabilitation programme or who have completed such a programme within 4 weeks before Visit 1 Known hypersensitivity to anticholinergic drugs or lactose

a.Z. VUB, Brussel 1090, Belgium

Boehringer Ingelheim Investigational Site, Hasselt 3500, Belgium

Boehringer Ingelheim Investigational Site, Genk 3600, Belgium

Sint-Elisabethziekenhuis, Turnhout 2300, Belgium

St. Elisabethziekenhuis, Herentals 2200, Belgium

Clinique Reine Astrid, Malmedy 4960, Belgium

CHU Sart Tilman, Angleur 4031, Belgium

Lungemedicinsk Klinik, Hvidovre DK-2650, Denmark

H:S Bispebjerg Hospital, K?benhavn NV 2400, Denmark

Lungemedicinsk Forskning 2B, Aarhus DK-8000, Denmark

Lungemedicinsk afdeling Y, Hellerup 2900, Denmark

Lungemedicinsk Forskning, Odense C 5000, Denmark

Medicinsk afdeling B0642, Hiller?d 3400, Denmark

Boehringer Ingelheim Investigational Site, Montpellier 34070, France

Hopital Arnaud de Villeneuve, Montpellier 34295, France

Boehringer Ingelheim Investigational Site, Chamalieres 66400, France

Boehringer Ingelheim Investigational Site, Nice 06000, France

Hopital d'Annecy, Annecy 74000, France

Hopital Prive Antony, Antony cedex 92166, France

Boehringer Ingelheim Investigational Site, Nantes 44000, France

Centre Medical Erdre St Augustin, Nantes 44000, France

Hopital Maison blanche, Reims cedex 51092, France

Hopital Notre Dame de Bon Secours, Metz cedex 1 57038, France

Hopital Gabriel Montpied, Clermont Ferrand cedex 1 63003, France

Hopital Ambroise Pare, Marseille 13291, France

Boehringer Ingelheim Investigational Site, Bonn 53119, Germany

MEDARS GmbH, Berlin 14057, Germany

Boehringer Ingelheim Investigational Site, Gelnhausen 63571, Germany

Boehringer Ingelheim Investigational Site, Furth 90762, Germany

Pneumologisches Forschungsinstitut GmbH am Krankenhaus, Hamburg 20535, Germany

Boehringer Ingelheim Investigational Site, Munchen 80335, Germany

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

Boehringer Ingelheim Investigational Site, Minden 32423, Germany

Boehringer Ingelheim Investigational Site, Frankfurt/Main 60323, Germany

Boehringer Ingelheim Investigational Site, Rudersdorf 15562, Germany

Boehringer Ingelheim Investigational Site, Berlin 12687, Germany

Boehringer Ingelheim Investigational Site, Berlin 12203, Germany

ClinPharm Internat. GmbH & Co. KG, Gorlitz 02826, Germany

Med. Einrichtung der Universitat zu Koln, Koln 50924, Germany

A.O. Pisana, PISA 56100, Italy

A.O. S. Martino e Cliniche Universitarie di Genova, GENOVA 16132, Italy

Universita di Genova, GENOVA 16132, Italy

A. O. Universitaria di Ferrara - Arcispedale S. Anna, Ferrara 44100, Italy

Amphia ziekenhuis, Breda 4819 EV, Netherlands

Antonius Ziekenhuis, Sneek 8601 ZK, Netherlands

Maxima Medisch Centrum, Velthoven 5505 DB, Netherlands

Atrium medisch centrum, Heerlen 6419 PC, Netherlands

Medisch Centrum Leeuwarden, Leeuwarden 8934 AD, Netherlands

Ziekenhuisgroep Twent, Almelo 7609 PP, Netherlands

Ziekenhuigroep Twente, Hengelo 7555 DL, Netherlands

Boehringer Ingelheim Investigational Site, Cape Town 7700, South Africa

Boehringer Ingelheim Investigational Site, Bellville 7530, South Africa

Boehringer Ingelheim Investigational Site, Pretoria 0001, South Africa

Boehringer Ingelheim Investigational Site, George 6529, South Africa

Boehringer Ingelheim Investigational Site, Durban 4001, South Africa

Boehringer Ingelheim Investigational Site, Paarl 7646, South Africa

Boehringer Ingelheim Investigational Site, Cape Town 8001, South Africa

Boehringer Ingelheim Investigational Site, Somerset West 7130, South Africa

VGH Research Pavillion, Vancouver, British Columbia V5Z 1L8, Canada

BG 034, Room C2027, Winnipeg, Manitoba R2H 2A6, Canada

Department of Respiratory Medicine, Toronto, Ontario M6M 2J5, Canada

Respiratory Research Lab, Toronto, Ontario M5T 2S8, Canada

Department of Medicine, Health Sciences Centre, Hamilton, Ontario L8N 3Z5, Canada

Boehringer Ingelheim Investigational Site, Toronto, Ontario M6H 3M2, Canada

Boehringer Ingelheim Investigational Site, Toronto, Ontario M5S 2A5, Canada

Boehringer Ingelheim Investigational Site, Mississauga, Ontario L5B 1N1, Canada

Centre de Recherche Clinique -CUSE, Sherbrooke, Quebec J1H 5N4, Canada

Hopital Laval, Ste-Foy, Quebec G1V 4G5, Canada

Ending date: April 2006
Last updated: March 17, 2008