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 II)

NCT00776984 | Completed Phase 3 Results

• 2 other identifiers: 205.4172008-001414-25
• Study Type: interventional
• Target: 453
• Locations: 15 countries
• Sites: 75

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 inhalation solution

tiotropium 5mcg/day

placebo DRUG

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

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 postbronchodilator 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 (75)

205.417.01061 Boehringer Ingelheim Investigational Site

Fountain Valley, California, United States

Location

205.417.01052 Boehringer Ingelheim Investigational Site

Fresno, California, United States

Location

205.417.01051 Boehringer Ingelheim Investigational Site

Stockton, California, United States

Location

205.417.01056 Boehringer Ingelheim Investigational Site

Waterbury, Connecticut, United States

Location

205.417.01065 Boehringer Ingelheim Investigational Site

Pensacola, Florida, United States

Location

205.417.01059 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

205.417.01068 Boehringer Ingelheim Investigational Site

Normal, Illinois, United States

Location

205.417.01063 Boehringer Ingelheim Investigational Site

Louisville, Kentucky, United States

Location

205.417.01064 Boehringer Ingelheim Investigational Site

New Orleans, Louisiana, United States

Location

205.417.01066 Boehringer Ingelheim Investigational Site

Omaha, Nebraska, United States

Location

205.417.01069 Boehringer Ingelheim Investigational Site

Ocean City, New Jersey, United States

Location

205.417.01062 Boehringer Ingelheim Investigational Site

Albany, New York, United States

Location

205.417.01058 Boehringer Ingelheim Investigational Site

Great Neck, New York, United States

Location

205.417.01055 Boehringer Ingelheim Investigational Site

Rockville Centre, New York, United States

Location

205.417.01067 Boehringer Ingelheim Investigational Site

High Point, North Carolina, United States

Location

205.417.01070 Boehringer Ingelheim Investigational Site

Canton, Ohio, United States

Location

205.417.01053 Boehringer Ingelheim Investigational Site

Upland, Pennsylvania, United States

Location

205.417.01054 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

Location

205.417.61051 Boehringer Ingelheim Investigational Site

Concord, New South Wales, Australia

Location

205.417.02051 Boehringer Ingelheim Investigational Site

Mississauga, Ontario, Canada

Location

205.417.02053 Boehringer Ingelheim Investigational Site

Ottawa, Ontario, Canada

Location

205.417.02052 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

205.417.45052 Boehringer Ingelheim Investigational Site

Aalborg, Denmark

Location

205.417.45051 Boehringer Ingelheim Investigational Site

Aarhus C, Denmark

Location

205.417.49052 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

205.417.49054 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

205.417.49053 Boehringer Ingelheim Investigational Site

Lübeck, Germany

Location

205.417.49051 Boehringer Ingelheim Investigational Site

Rüdersdorf, Germany

Location

205.417.49055 Boehringer Ingelheim Investigational Site

Weinheim, Germany

Location

205.417.39052 Boehringer Ingelheim Investigational Site

Bussolengo (vr), Italy

Location

205.417.39054 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

205.417.39051 Boehringer Ingelheim Investigational Site

Pavia, Italy

Location

205.417.39053 Boehringer Ingelheim Investigational Site

Pietra Ligure (sv), Italy

Location

205.417.81063 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, Japan

Location

205.417.81056 Boehringer Ingelheim Investigational Site

Hiroshima, Hiroshima, Japan

Location

205.417.81051 Boehringer Ingelheim Investigational Site

Itabashi-ku, Tokyo, Japan

Location

205.417.81059 Boehringer Ingelheim Investigational Site

Kagoshima, Kagoshima, Japan

Location

205.417.81053 Boehringer Ingelheim Investigational Site

Kishiwada, Osaka, Japan

Location

205.417.81057 Boehringer Ingelheim Investigational Site

Kitakyusyu, Fukuoka, Japan

Location

205.417.81058 Boehringer Ingelheim Investigational Site

Koga, Fukuoka, Japan

Location

205.417.81055 Boehringer Ingelheim Investigational Site

Kurashiki, Okayama, Japan

Location

205.417.81064 Boehringer Ingelheim Investigational Site

Kurume, Fukuoka, Japan

Location

205.417.81062 Boehringer Ingelheim Investigational Site

Morioka, Iwate, Japan

Location

205.417.81052 Boehringer Ingelheim Investigational Site

Osaka-sayama, Osaka, Japan

Location

205.417.81066 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, Japan

Location

205.417.81065 Boehringer Ingelheim Investigational Site

Seto, Aichi, Japan

Location

205.417.81060 Boehringer Ingelheim Investigational Site

Urasoe, Okinawa, Japan

Location

205.417.81061 Boehringer Ingelheim Investigational Site

Urasoe, Okinawa, Japan

Location

205.417.81054 Boehringer Ingelheim Investigational Site

Wakayama, Wakayama, Japan

Location

205.417.31051 Boehringer Ingelheim Investigational Site

Groningen, Netherlands

Location

205.417.31053 Boehringer Ingelheim Investigational Site

Leeuwarden, Netherlands

Location

205.417.31052 Boehringer Ingelheim Investigational Site

Schiedam, Netherlands

Location

205.417.64054 Boehringer Ingelheim Investigational Site

Auckland NZ, New Zealand

Location

205.417.64053 Boehringer Ingelheim Investigational Site

Christchurch, New Zealand

Location

205.417.64052 Boehringer Ingelheim Investigational Site

Newtown Wellington NZ, New Zealand

Location

205.417.64051 Boehringer Ingelheim Investigational Site

Tauranga, New Zealand

Location

205.417.07051 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.417.07052 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.417.07053 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.417.38153 Boehringer Ingelheim Investigational Site

Belgrade, Serbia

Location

205.417.38152 Boehringer Ingelheim Investigational Site

Kamenitz, Serbia

Location

205.417.38151 Boehringer Ingelheim Investigational Site

Niš, Serbia

Location

205.417.27051 Boehringer Ingelheim Investigational Site

Bellville, South Africa

Location

205.417.27052 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

205.417.27053 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

205.417.27054 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

205.417.90052 Boehringer Ingelheim Investigational Site

Ankara, Turkey (Türkiye)

Location

205.417.90053 Boehringer Ingelheim Investigational Site

Ankara, Turkey (Türkiye)

Location

205.417.90051 Boehringer Ingelheim Investigational Site

İzmit, Turkey (Türkiye)

Location

205.417.38053 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

Location

205.417.38051 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

Location

205.417.38052 Boehringer Ingelheim Investigational Site

Vinnytsia, Ukraine

Location

205.417.44051 Boehringer Ingelheim Investigational Site

Chertsey, United Kingdom

Location

205.417.44053 Boehringer Ingelheim Investigational Site

Exeter, United Kingdom

Location

205.417.44052 Boehringer Ingelheim Investigational Site

Windsor, 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 22, 2008
• Study Start: October 1, 2008
• Primary Completion: July 1, 2011
• Last Updated: September 10, 2014
• Results First Posted: September 27, 2012

Record last verified: 2014-09

Locations

NZ (4); AU (1); GB (3); US (18); UA (3); IT (4); DE (5); TU (3); JP (16); ZA (4); DK (2); SE (3); CA (3); NL (3); RU (3)