Randomised, Double- Blind, Cross-over Efficacy and Safety Comparison of Three Different Doses of Tiotropium Administered Once Daily Versus Placebo in Patients With Moderate Persistent Asthma.

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01233284
First received: November 2, 2010
Last updated: November 27, 2013
Last verified: September 2013
Results First Received: December 14, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Asthma
Interventions: Drug: tiotropium bromide 2.5µg once daily
Drug: Tiotropium matching Placebo once daily
Drug: tiotropium bromide high dose once daily
Drug: tiotropium bromide 1.25µg once daily

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 149 patients were randomised and treated, 141 patients completed the trial.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomised, double-blind, placebo controlled, cross-over design without washout phase between the four periods. Patients were randomized to one of the 4 sequences (ABCD, DCBA, BDAC, CADB). For one patient treatment 2 and treatment 3 were interchanged (resulting sequence DBCA).

Reporting Groups
  Description
Tio R5 Once Daily(qd)/Tio R1.25 qd/Placebo/Tio R2.5 qd Patients treated with Tiotropium 5 mcg in period 1 (evening), with Tiotropium 1.25 mcg in period 2 (evening), with a matching Placebo in period 3 (evening) and with Tiotropium 2.5 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to inhaled corticosteroids (ICS). No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
Tio R2.5 qd/Placebo/Tio R1.25 qd/Tio R5 qd Patients treated with Tiotropium 2.5 mcg in period 1 (evening), with a matching Placebo in period 2 (evening), with Tiotropium 1.25 mcg in period 3 (evening) and with Tiotropium 5 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
Tio R1.25 qd/Tio R2.5 qd/Tio R5 qd/Placebo Patients treated with Tiotropium 1.25 mcg in period 1 (evening), with Tiotropium 2.5 mcg in period 2 (evening), with Tiotropium 5 mcg in period 3 (evening) and with a matching placebo in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to inhaled corticosteroid ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
Placebo/Tio R5 qd/Tio R2.5 qd/Tio R1.25 qd Patients treated with a matching Placebo in period 1 (evening), with Tiotropium 5 mcg in period 2 (evening), with Tiotropium 2.5 mcg in period 3 (evening) and with Tiotropium 1.25 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.
Placebo/Tio R2.5 qd/Tio R5 qd/Tio R1.25 qd Patient treated with a matching Placebo in period 1 (evening), with Tiotropium 2.5 mcg in period 2 (evening), with Tiotropium 5 mcg in period 3 (evening) and with Tiotropium 1.25 mcg in period 4 (evening). All products were delivered by the Respimat inhaler as add-on therapy to ICS. No washouts (off-treatment periods) between treatments. Duration of each treatment period was 4 weeks.

Participant Flow for 4 periods

Period 1:   Period 1 (4 Weeks)
    Tio R5 Once Daily(qd)/Tio R1.25 qd/Placebo/Tio R2.5 qd     Tio R2.5 qd/Placebo/Tio R1.25 qd/Tio R5 qd     Tio R1.25 qd/Tio R2.5 qd/Tio R5 qd/Placebo     Placebo/Tio R5 qd/Tio R2.5 qd/Tio R1.25 qd     Placebo/Tio R2.5 qd/Tio R5 qd/Tio R1.25 qd  
STARTED     37     38     38     35     1  
COMPLETED     36     37     37     35     1  
NOT COMPLETED     1     1     1     0     0  
Lost to Follow-up                 1                 0                 0                 0                 0  
Withdrawal by Subject                 0                 1                 0                 0                 0  
Unknown                 0                 0                 1                 0                 0  

Period 2:   Period 2 (4 Weeks)
    Tio R5 Once Daily(qd)/Tio R1.25 qd/Placebo/Tio R2.5 qd     Tio R2.5 qd/Placebo/Tio R1.25 qd/Tio R5 qd     Tio R1.25 qd/Tio R2.5 qd/Tio R5 qd/Placebo     Placebo/Tio R5 qd/Tio R2.5 qd/Tio R1.25 qd     Placebo/Tio R2.5 qd/Tio R5 qd/Tio R1.25 qd  
STARTED     36     37     37     35     1  
COMPLETED     36     37     36     35     1  
NOT COMPLETED     0     0     1     0     0  
Withdrawal by Subject                 0                 0                 1                 0                 0  

Period 3:   Period 3 (4 Weeks)
    Tio R5 Once Daily(qd)/Tio R1.25 qd/Placebo/Tio R2.5 qd     Tio R2.5 qd/Placebo/Tio R1.25 qd/Tio R5 qd     Tio R1.25 qd/Tio R2.5 qd/Tio R5 qd/Placebo     Placebo/Tio R5 qd/Tio R2.5 qd/Tio R1.25 qd     Placebo/Tio R2.5 qd/Tio R5 qd/Tio R1.25 qd  
STARTED     36     37     36     35     1  
COMPLETED     36     37     35     34     1  
NOT COMPLETED     0     0     1     1     0  
Withdrawal by Subject                 0                 0                 1                 0                 0  
Unknown                 0                 0                 0                 1                 0  

Period 4:   Period 4 (4 Weeks)
    Tio R5 Once Daily(qd)/Tio R1.25 qd/Placebo/Tio R2.5 qd     Tio R2.5 qd/Placebo/Tio R1.25 qd/Tio R5 qd     Tio R1.25 qd/Tio R2.5 qd/Tio R5 qd/Placebo     Placebo/Tio R5 qd/Tio R2.5 qd/Tio R1.25 qd     Placebo/Tio R2.5 qd/Tio R5 qd/Tio R1.25 qd  
STARTED     36     37     35     34     1  
COMPLETED     36     36     35     33     1  
NOT COMPLETED     0     1     0     1     0  
Adverse Event                 0                 1                 0                 0                 0  
Lost to Follow-up                 0                 0                 0                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Baseline Total Total number of patients randomised and treated in the study.

Baseline Measures
    Baseline Total  
Number of Participants  
[units: participants]
  149  
Age  
[units: years]
Mean ± Standard Deviation
  49.3  ± 13.3  
Gender  
[units: Participants]
 
Female     82  
Male     67  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Forced Expiratory Volume in One Second (FEV1) Peak Within 0-3 Hours Post-dose Response   [ Time Frame: 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration ]

2.  Secondary:   Trough FEV1 Response   [ Time Frame: Baseline and 4 weeks ]

3.  Secondary:   FEV1 Area Under the Curve 0-3 Hours (AUC0-3h) Response   [ Time Frame: 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration ]

4.  Secondary:   Forced Vital Capacity (FVC) Peak Within 0-3 Hours Post-dose Response   [ Time Frame: 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration ]

5.  Secondary:   Trough FVC Response   [ Time Frame: Baseline and 4 weeks ]

6.  Secondary:   FVC AUC0-3h Response   [ Time Frame: 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration ]

7.  Secondary:   Individual FEV1 Over Time (at Each Timepoint at Visits) Response   [ Time Frame: Baseline and 4 weeks ]

8.  Secondary:   Individual FVC Over Time (at Each Timepoint at Visits) Response   [ Time Frame: Baseline and 4 weeks ]

9.  Secondary:   Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response   [ Time Frame: Baseline and 4 weeks ]

10.  Secondary:   Mean Pre-dose Morning PEF (PEF a.m.) Response During the Last Week on Treatment   [ Time Frame: Baseline and 4 weeks ]

11.  Secondary:   Mean Pre-dose Evening PEF (PEF p.m.) Response During the Last Week on Treatment   [ Time Frame: Baseline and 4 weeks ]

12.  Secondary:   PEF Variability Response (Last Week on Treatment)   [ Time Frame: Baseline and 4 weeks ]

13.  Secondary:   Mean Number of Puffs of Rescue Medication During the Whole Day (Last Week on Treatment, Response Values)   [ Time Frame: Baseline and 4 weeks ]

14.  Secondary:   Mean Number of Puffs of Rescue Medication During Daytime (Last Week on Treatment, Response Values)   [ Time Frame: Baseline and 4 weeks ]

15.  Secondary:   Mean Number of Puffs of Rescue Medication During Nighttime (Last Week on Treatment, Response Values)   [ Time Frame: Baseline and 4 weeks ]

16.  Secondary:   Mean Number of Night Awakenings During the Last Week on Treatment (Score, Response Values)   [ Time Frame: Baseline and 4 weeks ]

17.  Secondary:   FEV1 Area Under the Curve Within 24 Hours (h) Response (FEV1 AUC0-12h, FEV1 AUC12-24h, FEV1 AUC0-24h)   [ Time Frame: 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h, 4h, 11h 50min, 12h 30min, 13h, 14h, 15h, 16h, 18h, 20h, 22h, 23h, 23h 50min after drug administration ]

18.  Secondary:   FVC Area Under the Curve Within 24 Hours (h) Response (FVC AUC0-12h, FVC AUC12-24h, FVC AUC0-24h)   [ Time Frame: 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h, 4h, 11h 50min, 12h 30min, 13h, 14h, 15h, 16h, 18h, 20h, 22h, 23h, 23h 50min after drug administration ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided by Boehringer Ingelheim

Publications automatically indexed to this study:

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01233284     History of Changes
Other Study ID Numbers: 205.380, 2010-018471-26
Study First Received: November 2, 2010
Results First Received: December 14, 2012
Last Updated: November 27, 2013
Health Authority: Austria: Federal Office for Safety in Health Care
Germany: Federal Institute for Drugs and Medical Devices
Ukraine: State Pharmacological Center - Ministry of Health