Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I)

NCT00772538 | Completed Phase 3 Results

• 2 other identifiers: 205.4162008-001413-14
• Study Type: interventional
• Target: 459
• Locations: 14 countries
• Sites: 73

Brief Summary

The trial is a randomised, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of 5 µg tiotropium over a 48-week treatment period as compared to placebo. Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined as add-on controller therapy on top of usual care in patients with severe persistent asthma. The primary objective of each trial is to evaluate the long term efficacy of tiotropium over placebo on top of usual care in patients with severe persistent asthma as determined by pulmonary function testing, effects on asthma exacerbations, effects on quality of life, on asthma control and health care resource utilisation. The secondary objective of each trial is to compare the long term safety of tiotropium with placebo in this patient population.

Conditions

Asthma

Outcome Measures

Primary Outcomes (3)

• Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 24 Weeks.

  Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

  Baseline and 24 weeks

• Trough FEV1 Response Determined After a Treatment Period of 24 Weeks.

  The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 24 weeks and the FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment\*visit and baseline\*visit.

  Baseline and 24 weeks

• Time to First Severe Asthma Exacerbation During the 48-week Treatment of the Pooled Data From the Two Twin Trials 205.416 (NCT00772538) and the Present 205.417 (NCT00776984).

  Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.

  48 weeks

Secondary Outcomes (29)

• Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 24-week Treatment Period.

  Baseline and 24 weeks

• Trough FVC Response at the End of the 24-week Treatment Period.

  Baseline and 24 weeks

• FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 24-week Treatment Period.

  Baseline and 24 weeks

• FVC (AUC0-3h) Response at the End of the 24-week Treatment Period.

  Baseline and 24 weeks

• Peak FEV1 0-3h Response at the End of the 48-week Treatment Period.

  Baseline and 48 weeks

Study Arms (2)

tiotropium 5mcg/day

EXPERIMENTAL

patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Drug: tiotropium 5mcg/day

placebo

EXPERIMENTAL

patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Drug: placebo

Interventions

tiotropium 5mcg/day DRUG

Intervention = randomisation: Patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo

tiotropium 5mcg/day

placebo DRUG

Matching placebo

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).
• Male or female patients aged at least 18 years but not more than 75 years.
• All patients must have at least a 5-year history of asthma at the time of enrolment into the trial and the diagnosis of asthma must have been made before the patient´s age of 40.
• All patients must have a diagnosis of severe persistent asthma and must be symptomatic despite treatment with high, stable doses of inhaled corticosteroids and a long-acting beta adrenergic agent
• All patients must have a history of one or more asthma exacerbation in the past year.
• Patients must have evidence of treated, severe, persistent asthma in postbronchodilatory pulmonary function tests.
• Patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment and who have a smoking history of less than 10 pack years
• Patients must be able to use the Respimat® inhaler correctly
• Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the electronic diary/peak flow meter.

You may not qualify if:

• Patients with a significant disease other than asthma. A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient´s ability to participate in the trial.
• Patients with clinically relevant abnormal screening haematology or blood chemistry.
• Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1).
• Patients using oral corticosteroid medication at stable doses exceeding 5 mg prednisolone or prednisolone equivalent every day or 10 mg prednisolone or prednisolone equivalent every second day.
• Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.
• Pregnant or nursing women or women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.
• Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.
• Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®), beta-blocker medication, oral beta-adrenergics, other non-approved and according to international guidelines not recommended ´experimental´ drugs for routine asthma therapy (e.g. TNF-alpha blockers, methotrexate, cyclosporin) within four weeks prior to the Screening Visit (Visit 1) or during the screening period.
• Patients with any asthma exacerbation or respiratory tract infection in the four weeks prior to the trial.
• Patients who have previously been randomised in this trial or in the respective twin trial (205.416 versus 205.417) or are currently participating in another trial.
• Patients with a known narrow-angle glaucoma.
• Note:
• As with other anticholinergic drugs, tiotropium should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.
• As with all predominantly renally excreted drugs, patients with moderate to severe renal impairment (known creatinine clearance of \<= 50 mL/min) treated with tiotropium should be monitored closely.

Sponsors & Collaborators

• Boehringer Ingelheim: lead
• Pfizer: collaborator

Study Sites (73)

205.416.01007 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Location

205.416.01012 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

205.416.01018 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

205.416.01016 Boehringer Ingelheim Investigational Site

Riverside, California, United States

Location

205.416.01008 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Location

205.416.01004 Boehringer Ingelheim Investigational Site

Walnut Creek, California, United States

Location

205.416.01010 Boehringer Ingelheim Investigational Site

Stamford, Connecticut, United States

Location

205.416.01023 Boehringer Ingelheim Investigational Site

Tallahassee, Florida, United States

Location

205.416.01002 Boehringer Ingelheim Investigational Site

Elk Grove Village, Illinois, United States

Location

205.416.01003 Boehringer Ingelheim Investigational Site

Lexington, Kentucky, United States

Location

205.416.01014 Boehringer Ingelheim Investigational Site

Wheaton, Maryland, United States

Location

205.416.01025 Boehringer Ingelheim Investigational Site

North Dartmouth, Massachusetts, United States

Location

205.416.01022 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

Location

205.416.01021 Boehringer Ingelheim Investigational Site

Boys Town, Nebraska, United States

Location

205.416.01011 Boehringer Ingelheim Investigational Site

Cherry Hill, New Jersey, United States

Location

205.416.01001 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

Location

205.416.01024 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

205.416.01017 Boehringer Ingelheim Investigational Site

Lake Oswego, Oregon, United States

Location

205.416.01019 Boehringer Ingelheim Investigational Site

El Paso, Texas, United States

Location

205.416.01009 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

Location

205.416.61001 Boehringer Ingelheim Investigational Site

Daw Park, South Australia, Australia

Location

205.416.61002 Boehringer Ingelheim Investigational Site

Woodville, South Australia, Australia

Location

205.416.61003 Boehringer Ingelheim Investigational Site

Nedlands, Western Australia, Australia

Location

205.416.02001 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

205.416.02002 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

205.416.02003 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

205.416.02004 Boehringer Ingelheim Investigational Site

Québec, Quebec, Canada

Location

205.416.45001 Boehringer Ingelheim Investigational Site

Hvidovre, Denmark

Location

205.416.45002 Boehringer Ingelheim Investigational Site

Odense C, Denmark

Location

205.416.49002 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.416.49003 Boehringer Ingelheim Investigational Site

Gelnhausen, Germany

Location

205.416.49005 Boehringer Ingelheim Investigational Site

Koblenz, Germany

Location

205.416.49004 Boehringer Ingelheim Investigational Site

Oschersleben, Germany

Location

205.416.39001 Boehringer Ingelheim Investigational Site

Pisa, Italy

Location

205.416.39002 Boehringer Ingelheim Investigational Site

Sesto S. Giovanni (MI), Italy

Location

205.416.81007 Boehringer Ingelheim Investigational Site

Hachioji, Tokyo, Japan

Location

205.416.81004 Boehringer Ingelheim Investigational Site

Inashiki-gun, Ibaraki, Japan

Location

205.416.81006 Boehringer Ingelheim Investigational Site

Kamogawa, Chiba, Japan

Location

205.416.81012 Boehringer Ingelheim Investigational Site

Maebashi, Gunma, Japan

Location

205.416.81008 Boehringer Ingelheim Investigational Site

Minato-ku, Tokyo, Japan

Location

205.416.81009 Boehringer Ingelheim Investigational Site

Minato-ku, Tokyo, Japan

Location

205.416.81001 Boehringer Ingelheim Investigational Site

Naka-gun, Ibaraki, Japan

Location

205.416.81014 Boehringer Ingelheim Investigational Site

Noda, Chiba, Japan

Location

205.416.81015 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, Japan

Location

205.416.81016 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, Japan

Location

205.416.81002 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, Japan

Location

205.416.81010 Boehringer Ingelheim Investigational Site

Shinagawa-ku, Tokyo, Japan

Location

205.416.81005 Boehringer Ingelheim Investigational Site

Tsukuba, Ibaraki, Japan

Location

205.416.81011 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, Japan

Location

205.416.81003 Boehringer Ingelheim Investigational Site

Yonezawa, Yamagata, Japan

Location

205.416.31005 Boehringer Ingelheim Investigational Site

Breda, Netherlands

Location

205.416.31001 Boehringer Ingelheim Investigational Site

Groningen, Netherlands

Location

205.416.31004 Boehringer Ingelheim Investigational Site

Helmond, Netherlands

Location

205.416.31003 Boehringer Ingelheim Investigational Site

Zutphen, Netherlands

Location

205.416.07001 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.416.07002 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.416.07003 Boehringer Ingelheim Investigational Site

Reutov - Moscow Region, Russia

Location

205.416.38101 Boehringer Ingelheim Investigational Site

Belgrade, Serbia

Location

205.416.38102 Boehringer Ingelheim Investigational Site

Kragujevac, Serbia

Location

205.416.38103 Boehringer Ingelheim Investigational Site

Zemun, Serbia

Location

205.416.27001 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

205.416.27002 Boehringer Ingelheim Investigational Site

Durban, South Africa

Location

205.416.27003 Boehringer Ingelheim Investigational Site

Durban, South Africa

Location

205.416.27004 Boehringer Ingelheim Investigational Site

Pretoria, South Africa

Location

205.416.90001 Boehringer Ingelheim Investigational Site

Istanbul, Turkey (Türkiye)

Location

205.416.90002 Boehringer Ingelheim Investigational Site

Izmir, Turkey (Türkiye)

Location

205.416.38002 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

Location

205.416.38001 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

205.416.38003 Boehringer Ingelheim Investigational Site

Vinnytsia, Ukraine

Location

205.416.44003 Boehringer Ingelheim Investigational Site

Brighton, United Kingdom

Location

205.416.44002 Boehringer Ingelheim Investigational Site

Leicester, United Kingdom

Location

205.416.44004 Boehringer Ingelheim Investigational Site

Nottingham, United Kingdom

Location

205.416.44005 Boehringer Ingelheim Investigational Site

Nottingham, United Kingdom

Location

Related Publications (4)

• Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

  PMID: 36472162 DERIVED

• Halpin DMG, Meltzer EO, Pisternick-Ruf W, Moroni-Zentgraf P, Engel M, Zaremba-Pechmann L, Casale T, FitzGerald JM. Peak expiratory flow as an endpoint for clinical trials in asthma: a comparison with FEV1. Respir Res. 2019 Jul 18;20(1):159. doi: 10.1186/s12931-019-1119-6.

  PMID: 31319851 DERIVED

• Casale TB, Bateman ED, Vandewalker M, Virchow JC, Schmidt H, Engel M, Moroni-Zentgraf P, Kerstjens HAM. Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype. J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):923-935.e9. doi: 10.1016/j.jaip.2017.08.037. Epub 2017 Nov 22.

  PMID: 29174062 DERIVED

• Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 27;367(13):1198-207. doi: 10.1056/NEJMoa1208606. Epub 2012 Sep 2.

  PMID: 22938706 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2008
• First Posted: October 15, 2008
• Study Start: October 1, 2008
• Primary Completion: July 1, 2011
• Last Updated: August 18, 2014
• Results First Posted: September 27, 2012

Record last verified: 2014-07

Locations

GB (4); AU (3); CA (4); US (20); NL (4); DE (4); SE (3); ZA (4); JP (15); TU (2); RU (3); IT (2); DK (2); UA (3)