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Tiotropium+Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01431274
First received: September 8, 2011
Last updated: June 19, 2015
Last verified: June 2015
Results First Received: June 19, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Treatment
Condition: Pulmonary Disease, Chronic Obstructive
Interventions: Drug: tiotropium + olodaterol
Drug: tiotropium
Drug: olodaterol
Device: Respimat

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This trial was one of 2 confirmatory Phase III 52-week, multi-centre, multi-national, randomised,double-blind, parallel group studies to evaluate the long-term efficacy and safety of once daily treatment with orally inhaled Tio+Olo FDC (2.5/5μg; 5/5μg) compared with the individual components (2.5μg; 5μg Tiotropium, 5μg Olodaterol) in COPD patients

Reporting Groups
  Description
Olodaterol (5 μg) Oral inhalation of Olodaterol 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tiotropium (2.5 μg) Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tiotropium (5 μg) Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tio+Olo FDC (2.5/5 μg) Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tio+Olo FDC (5/5 μg) Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.

Participant Flow:   Overall Study
    Olodaterol (5 μg)   Tiotropium (2.5 μg)   Tiotropium (5 μg)   Tio+Olo FDC (2.5/5 μg)   Tio+Olo FDC (5/5 μg)
STARTED   528   525   527   522   522 
COMPLETED   431   448   455   462   466 
NOT COMPLETED   97   77   72   60   56 
Adverse Event                51                37                43                30                37 
Consent withdrawn not due to AE                29                20                17                20                11 
Non compliant with protocol                5                8                4                4                4 
Lost to Follow-up                6                7                1                4                0 
Other reason not stated above                6                5                7                2                4 



  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.
Treated set (TS): This patient set included all patients in the randomised set who were dispensed study medication and were documented to have taken any dose of study medication.

Reporting Groups
  Description
Olodaterol (5 μg) Oral inhalation of Olodaterol 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tiotropium (2.5 μg) Oral inhalation of Tiotropium 2.5 μg (1.25 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tiotropium (5 μg) Oral inhalation of Tiotropium 5 μg (2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tio+Olo FDC (2.5/5 μg) Oral inhalation of fixed dose combination (FDC) of Tiotropium 2.5 μg and Olodaterol 5 μg (Tiotropium: 1.25 μg per actuation and Olodaterol: 2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Tio+Olo FDC (5/5 μg) Oral inhalation of FDC of Tiotropium 5 μg and Olodaterol 5 μg (Tiotropium and Olodaterol: 2.5 μg per actuation) , 2 puffs from the RESPIMAT inhaler, once daily, in the morning.
Total Total of all reporting groups

Baseline Measures
   Olodaterol (5 μg)   Tiotropium (2.5 μg)   Tiotropium (5 μg)   Tio+Olo FDC (2.5/5 μg)   Tio+Olo FDC (5/5 μg)   Total 
Overall Participants Analyzed 
[Units: Participants]
 528   525   527   522   522   2624 
Age 
[Units: Years]
Mean (Standard Deviation)
 63.7  (8.0)   64.2  (8.6)   64.2  (8.5)   64.1  (8.0)   64.8  (8.2)   64.2  (8.3) 
Gender 
[Units: Participants]
           
Female   142   133   144   133   138   690 
Male   386   392   383   389   384   1934 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169. ]

2.  Primary:   Trough FEV1 Response on Day 170.   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170 ]

3.  Primary:   Saint George’s Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: Day 169 ]

4.  Secondary:   Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: Day 169 ]

5.  Secondary:   FEV1 AUC(0-3h) Response on Day 1   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment. ]

6.  Secondary:   FEV1 AUC(0-3h) Response on Day 85   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85. ]

7.  Secondary:   FEV1 AUC(0-3h) Response on Day 365   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365. ]

8.  Secondary:   Trough FEV1 Response on Day 15.   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15 ]

9.  Secondary:   Trough FEV1 Response on Day 43   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43. ]

10.  Secondary:   Trough FEV1 Response on Day 85   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 85. ]

11.  Secondary:   Trough FEV1 Response on Day 169   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on Day 169 ]

12.  Secondary:   Trough FEV1 Response on Day 365   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 365 ]

13.  Secondary:   FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment. ]

14.  Secondary:   FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85. ]

15.  Secondary:   FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 169   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169. ]

16.  Secondary:   FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365. ]

17.  Secondary:   Trough FVC Response on Day 15.   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15 ]

18.  Secondary:   Trough FVC Response on Day 43.   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43 ]

19.  Secondary:   Trough FVC Response on Day 85.   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85 ]

20.  Secondary:   Trough FVC Response on Day 170.   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170 ]

21.  Secondary:   Trough FVC Response on Day 365.   [ Time Frame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on Day 365. ]

22.  Secondary:   FEV1 AUC(0-12h) Response in the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169. ]

23.  Secondary:   FEV1 AUC(0-24h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169. ]

24.  Secondary:   FVC AUC(0-12h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169. ]

25.  Secondary:   FVC AUC(0-24h) Response in Sub-set of Patients With 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: 1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169. ]

26.  Secondary:   Saint George’s Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: Day 85 ]

27.  Secondary:   Saint George’s Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: Day 365 ]

28.  Secondary:   Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: Day 43 ]

29.  Secondary:   Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: Day 85 ]

30.  Secondary:   Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)   [ Time Frame: Day 365 ]


  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
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01431274     History of Changes
Other Study ID Numbers: 1237.5
2009-010668-40 ( EudraCT Number: EudraCT )
Study First Received: September 8, 2011
Results First Received: June 19, 2015
Last Updated: June 19, 2015
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Responsible Ethics Committee
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control
Denmark: The Danish Health and Medicines Authority
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Agence Nationale sécurité médicament et des produits santé
Germany: Federal Institute for Drugs and Medical Devices
Guatemala: Ministry of Public Health and Social Assistance
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Italy: Ethics Committee
Japan: Ministry of Health, Labor and Welfare
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Medsafe
Portugal: National Pharmacy and Medicines Institute
Russia: Pharmacological Committee, Ministry of Health
Slovenia: Agency for Medicinal Products - Ministry of Health
South Korea: Ministry of Food and Drug Safety (MFDS)
Turkey: Ministry of Health
United States: Food and Drug Administration