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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00776984




Registration number
NCT00776984
Ethics application status
Date submitted
13/10/2008
Date registered
22/10/2008
Date last updated
10/09/2014

Titles & IDs
Public title
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)
Scientific title
A Phase III Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (5 mcg/Day) Over 48 Weeks as add-on Controller Therapy on Top of Usual Care in Patients With Severe Persistent Asthma
Secondary ID [1] 0 0
2008-001414-25
Secondary ID [2] 0 0
205.417
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tiotropium 5mcg/day
Treatment: Drugs - placebo

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

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


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

Treatment: Drugs: placebo
Intervention = Randomisation: patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 24 Weeks.
Timepoint [1] 0 0
Baseline and 24 weeks
Primary outcome [2] 0 0
Trough FEV1 Response Determined After a Treatment Period of 24 Weeks.
Timepoint [2] 0 0
Baseline and 24 weeks
Primary outcome [3] 0 0
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).
Timepoint [3] 0 0
48 weeks
Secondary outcome [1] 0 0
Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 24-week Treatment Period.
Timepoint [1] 0 0
Baseline and 24 weeks
Secondary outcome [2] 0 0
Trough FVC Response at the End of the 24-week Treatment Period.
Timepoint [2] 0 0
Baseline and 24 weeks
Secondary outcome [3] 0 0
FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 24-week Treatment Period.
Timepoint [3] 0 0
Baseline and 24 weeks
Secondary outcome [4] 0 0
FVC (AUC0-3h) Response at the End of the 24-week Treatment Period.
Timepoint [4] 0 0
Baseline and 24 weeks
Secondary outcome [5] 0 0
Peak FEV1 0-3h Response at the End of the 48-week Treatment Period.
Timepoint [5] 0 0
Baseline and 48 weeks
Secondary outcome [6] 0 0
Trough FEV1 Response at the End of the 48-week Treatment Period.
Timepoint [6] 0 0
Baseline and 48 weeks
Secondary outcome [7] 0 0
AUC0-3h FEV1 Response at the End of the 48-week Treatment Period.
Timepoint [7] 0 0
Baseline and 48 weeks
Secondary outcome [8] 0 0
Peak FVC 0-3h Response at the End of the 48-week Treatment Period.
Timepoint [8] 0 0
Baseline and 48 weeks
Secondary outcome [9] 0 0
Trough FVC Response at the End of the 48-week Treatment Period.
Timepoint [9] 0 0
Baseline and 48 weeks
Secondary outcome [10] 0 0
FVC AUC0-3h Response at the End of the 48-week Treatment Period.
Timepoint [10] 0 0
Baseline and 48 weeks
Secondary outcome [11] 0 0
Mean Pre-dose Morning Peak Expiratory Flow (PEFa.m.) Response (Diary Data) of Last-7-days-before-week-24-visit .
Timepoint [11] 0 0
Baseline and last 7 days before week 24 visit
Secondary outcome [12] 0 0
Mean Pre-dose Evening Peak Expiratory Flow (PEFp.m.) Response (Diary Data) of Last-7-days-before-week 24-visit.
Timepoint [12] 0 0
Baseline and last 7 days before week 24 visit
Secondary outcome [13] 0 0
Mean Pre-dose FEV1 a.m. Response (Diary Data) of Last-7-days-before-week 24-visit.
Timepoint [13] 0 0
Baseline and last 7 days before week 24 visit
Secondary outcome [14] 0 0
Mean Pre-dose FEV1-p.m.Response (Diary Data) of Last-7-days-before-week 24-visit.
Timepoint [14] 0 0
Baseline and last 7 days before week 24 visit
Secondary outcome [15] 0 0
Mean PEF Variability Response (Absolute Difference Between Morning and Evening PEF Value Divided by Their Mean) of Last-7-days-before-week 24-visit.
Timepoint [15] 0 0
Baseline and last 7 days before week 24 visit
Secondary outcome [16] 0 0
Time to First Severe Asthma Exacerbation During the 48-week Treatment.
Timepoint [16] 0 0
48 weeks
Secondary outcome [17] 0 0
Number of Asthma Exacerbations Per Patient During the 48-week Treatment Period.
Timepoint [17] 0 0
48 weeks
Secondary outcome [18] 0 0
Number of Severe Asthma Exacerbations Per Patient During the 48-week Treatment Period.
Timepoint [18] 0 0
48 weeks
Secondary outcome [19] 0 0
Number of Patients With at Least One Asthma Exacerbation During the 48-week Treatment Period.
Timepoint [19] 0 0
48 weeks
Secondary outcome [20] 0 0
Number of Patients With at Least One Severe Asthma Exacerbation During the 48-week Treatment Period.
Timepoint [20] 0 0
48 weeks
Secondary outcome [21] 0 0
Time to First Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.
Timepoint [21] 0 0
48 weeks
Secondary outcome [22] 0 0
Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period.
Timepoint [22] 0 0
48 weeks
Secondary outcome [23] 0 0
Number of Patients With at Least One Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.
Timepoint [23] 0 0
48 weeks
Secondary outcome [24] 0 0
Quality of Life as Assessed by Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) at the End of the 24-week Treatment Period.
Timepoint [24] 0 0
24 weeks
Secondary outcome [25] 0 0
AQLQ(S) Total Score at the End of the 48-week Treatment Period.
Timepoint [25] 0 0
48 weeks
Secondary outcome [26] 0 0
Asthma Control as Assessed by Asthma Control Questionnaire (ACQ) at the End of the 24-week Treatment Period.
Timepoint [26] 0 0
24 weeks
Secondary outcome [27] 0 0
ACQ Score at the End of the 48-week Treatment Period.
Timepoint [27] 0 0
48 weeks
Secondary outcome [28] 0 0
Asthma Symptom Free Days Response During the Last-7-days-before-week-24-visit .
Timepoint [28] 0 0
Baseline and last 7 days before week 24 visit
Secondary outcome [29] 0 0
Mean Pro Re Nata (as Needed, PRN) Rescue Medication Use Response During the Last-7-days-before-week-24-visit .
Timepoint [29] 0 0
Baseline and last 7 days before week 24 visit

Eligibility
Key inclusion criteria
Inclusion criteria:

1. 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).
2. Male or female patients aged at least 18 years but not more than 75 years.
3. 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.
4. 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
5. All patients must have a history of one or more asthma exacerbation in the past year.
6. Patients must have evidence of treated, severe, persistent asthma in postbronchodilator pulmonary function tests.
7. 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
8. Patients must be able to use the Respimat® inhaler correctly
9. 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. 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.
2. Patients with clinically relevant abnormal screening haematology or blood chemistry.
3. Patients with a recent history (i.e. six months or less) of myocardial infarction, hospitalisation for cardiac failure during the past year, any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year, known active tuberculosis, malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (treated basal cell carcinoma allowed), lung diseases other than asthma (e.g. COPD), significant alcohol or drug abuse within the past two years, patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1.
4. 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).
5. 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.
6. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.
7. 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.
8. Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.
9. 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.
10. Patients with any asthma exacerbation or respiratory tract infection in the four weeks prior to the trial.
11. 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.
12. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
453
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
205.417.61051 Boehringer Ingelheim Investigational Site - Concord
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Nebraska
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Denmark
State/province [16] 0 0
Aalborg
Country [17] 0 0
Denmark
State/province [17] 0 0
Aarhus C
Country [18] 0 0
Germany
State/province [18] 0 0
Berlin
Country [19] 0 0
Germany
State/province [19] 0 0
Hamburg
Country [20] 0 0
Germany
State/province [20] 0 0
Lübeck
Country [21] 0 0
Germany
State/province [21] 0 0
Rüdersdorf
Country [22] 0 0
Germany
State/province [22] 0 0
Weinheim
Country [23] 0 0
Italy
State/province [23] 0 0
Bussolengo (vr)
Country [24] 0 0
Italy
State/province [24] 0 0
Milano
Country [25] 0 0
Italy
State/province [25] 0 0
Pavia
Country [26] 0 0
Italy
State/province [26] 0 0
Pietra Ligure (sv)
Country [27] 0 0
Japan
State/province [27] 0 0
Himeji, Hyogo
Country [28] 0 0
Japan
State/province [28] 0 0
Hiroshima, Hiroshima
Country [29] 0 0
Japan
State/province [29] 0 0
Itabashi-ku, Tokyo
Country [30] 0 0
Japan
State/province [30] 0 0
Kagoshima, Kagoshima
Country [31] 0 0
Japan
State/province [31] 0 0
Kishiwada, Osaka
Country [32] 0 0
Japan
State/province [32] 0 0
Kitakyusyu, Fukuoka
Country [33] 0 0
Japan
State/province [33] 0 0
Koga, Fukuoka
Country [34] 0 0
Japan
State/province [34] 0 0
Kurashiki, Okayama
Country [35] 0 0
Japan
State/province [35] 0 0
Kurume, Fukuoka
Country [36] 0 0
Japan
State/province [36] 0 0
Morioka, Iwate
Country [37] 0 0
Japan
State/province [37] 0 0
Osaka-sayama, Osaka
Country [38] 0 0
Japan
State/province [38] 0 0
Sendai, Miyagi
Country [39] 0 0
Japan
State/province [39] 0 0
Seto, Aichi
Country [40] 0 0
Japan
State/province [40] 0 0
Urasoe, Okinawa
Country [41] 0 0
Japan
State/province [41] 0 0
Wakayama, Wakayama
Country [42] 0 0
Netherlands
State/province [42] 0 0
Groningen
Country [43] 0 0
Netherlands
State/province [43] 0 0
Leeuwarden
Country [44] 0 0
Netherlands
State/province [44] 0 0
Schiedam
Country [45] 0 0
New Zealand
State/province [45] 0 0
Auckland NZ
Country [46] 0 0
New Zealand
State/province [46] 0 0
Christchurch
Country [47] 0 0
New Zealand
State/province [47] 0 0
Newtown Wellington NZ
Country [48] 0 0
New Zealand
State/province [48] 0 0
Tauranga
Country [49] 0 0
Russian Federation
State/province [49] 0 0
St. Petersburg
Country [50] 0 0
Serbia
State/province [50] 0 0
Belgrade
Country [51] 0 0
Serbia
State/province [51] 0 0
Nis
Country [52] 0 0
Serbia
State/province [52] 0 0
Sremska Kamenica
Country [53] 0 0
South Africa
State/province [53] 0 0
Bellville
Country [54] 0 0
South Africa
State/province [54] 0 0
Cape Town
Country [55] 0 0
Turkey
State/province [55] 0 0
Ankara
Country [56] 0 0
Turkey
State/province [56] 0 0
Izmit
Country [57] 0 0
Ukraine
State/province [57] 0 0
Kharkov
Country [58] 0 0
Ukraine
State/province [58] 0 0
Kiev
Country [59] 0 0
Ukraine
State/province [59] 0 0
Vinnytsya
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Chertsey
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Exeter
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Windsor

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Pfizer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00776984
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00776984