Respimat® Combivent Trial in Chronic Obstructive Pulmonary Disease (COPD) - Study Results

Study Type:	Interventional
Condition:	Pulmonary Disease, Chronic Obstructive
Interventions:	Drug: Atrovent Respimat (20 mcg) plus placebo COMBIVENT MDI Drug: COMBIVENT MDI (36/206 mcg ) plus placebo Combivent Respimat Drug: Combivent Respimat (20 mcg/100 mcg) plus placebo COMBIVENT MDI

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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	COMBIVENT Respimat 20/100 Mcg	COMBIVENT CFC-MDI 36/206 Mcg	Ipratropium Respimat 20 Mcg
STARTED	486	491	483
COMPLETED	438	436	422
NOT COMPLETED	48	55	61

	COMBIVENT Respimat 20/100 Mcg	COMBIVENT CFC-MDI 36/206 Mcg	Ipratropium Respimat 20 Mcg	Total
Number of Participants [units: participants]	486	491	483	1460
Age [units: years] Mean ± Standard Deviation	63.8 ± 8.7	64.2 ± 9.2	64.3 ± 8.6	64.1 ± 8.8
Gender [units: participants]
Female	170	169	166	505
Male	316	322	317	955

Outcome Measures

Show All Outcome Measures

1. Primary:

FEV1 AUC0-6 at Day 85 [ Before drug administration to 6 hours after drug administration on Day 85 ]

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2. Primary:

FEV1 AUC0-4 at Day 85 [ Before drug administration to 4 hours after drug administration on Day 85 ]

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3. Primary:

FEV1 AUC4-6 at Day 85 [ Between 4 hours and 6 hours after drug administration on Day 85 ]

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4. Secondary:

FEV1 AUC0-6 at Day 1 [ Before drug administration to 6 hours after drug administration on Day 1 ]

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5. Secondary:

FEV1 AUC0-6 at Day 29 [ Before drug administration to 6 hours after drug administration on Day 29 ]

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6. Secondary:

FEV1 AUC0-6 at Day 57 [ Before drug administration to 6 hours after drug administration on Day 57 ]

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7. Secondary:

FEV1 AUC0-4 at Day 1 [ Before drug administration to 4 hours after drug administration on Day 1 ]

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8. Secondary:

FEV1 AUC0-4 at Day 29 [ Before drug administration to 4 hours after drug administration on Day 29 ]

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9. Secondary:

FEV1 AUC0-4 at Day 57 [ Before drug administration to 4 hours after drug administration on Day 57 ]

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10. Secondary:

FEV1 AUC4-6 at Day 1 [ Between 4 hours and 6 hours after drug administration on Day 1 ]

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11. Secondary:

FEV1 AUC4-6 at Day 29 [ Between 4 hours and 6 hours after drug administration on Day 29 ]

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12. Secondary:

FEV1 AUC4-6 at Day 57 [ Between 4 hours and 6 hours after drug administration on Day 57 ]

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13. Secondary:

Peak FEV1 Response at Day 1 [ Within the first 2-hour post-treatment interval on Day 1 ]

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14. Secondary:

Peak FEV1 Response at Day 29 [ Within the first 2-hour post-treatment interval on Day 29 ]

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15. Secondary:

Peak FEV1 Response at Day 57 [ Within the first 2-hour post-treatment interval on Day 57 ]

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16. Secondary:

Peak FEV1 Response at Day 85 [ Within the first 2-hour post-treatment interval on Day 85 ]

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17. Secondary:

Peak FEV1 Response at Day 1 [ Within the first 2-hour post-treatment interval on Day 1 ]

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18. Secondary:

Peak FEV1 Response at Day 29 [ Within the first 2-hour post-treatment interval on Day 29 ]

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19. Secondary:

Peak FEV1 Response at Day 57 [ Within the first 2-hour post-treatment interval on Day 57 ]

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20. Secondary:

Peak FEV1 Response at Day 85 [ Within the first 2-hour post-treatment interval on Day 85 ]

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21. Secondary:

Time to Onset of Therapeutic FEV1 Response at Day 1 [ Within the first 2-hour post-treatment interval at Day 1 ]

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22. Secondary:

Time to Onset of Therapeutic FEV1 Response at Day 29 [ Within the first 2-hour post-treatment interval at Day 29 ]

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23. Secondary:

Time to Onset of Therapeutic FEV1 Response at Day 57 [ Within the first 2-hour post-treatment interval at Day 57 ]

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24. Secondary:

Time to Onset of Therapeutic FEV1 Response at Day 85 [ Within the first 2-hour post-treatment interval at Day 85 ]

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25. Secondary:

Duration of Therapeutic FEV1 Response at Day 1 [ During the 6-hour observation period after drug administration at Day 1 ]

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26. Secondary:

Duration of Therapeutic FEV1 Response at Day 29 [ During the 6-hour observation period after drug administration at Day 29 ]

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27. Secondary:

Duration of Therapeutic FEV1 Response at Day 57 [ During the 6-hour observation period after drug administration at Day 57 ]

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28. Secondary:

Duration of Therapeutic FEV1 Response at Day 85 [ During the 6-hour observation period after drug administration at Day 85 ]

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29. Secondary:

Time to Peak FEV1 Response at Day 1 [ Within the 6-hour post-treatment observation period at Day 1 ]

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30. Secondary:

Time to Peak FEV1 Response at Day 29 [ Within the 6-hour post-treatment observation period at Day 29 ]

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31. Secondary:

Time to Peak FEV1 Response at Day 57 [ Within the 6-hour post-treatment observation period at Day 57 ]

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32. Secondary:

Time to Peak FEV1 Response at Day 85 [ Within the 6-hour post-treatment observation period at Day 85 ]

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33. Secondary:

FVC AUC0-6 at Day 1 [ Before drug administration to 6 hours after drug administration at Day 1 ]

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34. Secondary:

FVC AUC0-6 at Day 29 [ Before drug administration to 6 hours after drug administration at Day 29 ]

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35. Secondary:

FVC AUC0-6 at Day 57 [ Before drug administration to 6 hours after drug administration on Day 57 ]

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36. Secondary:

FVC AUC0-6 at Day 85 [ Before drug administration to 6 hours after drug administration on Day 85 ]

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37. Secondary:

FVC AUC0-4 at Day 1 [ Before drug administration to 4 hours after drug administration on Day 1 ]

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38. Secondary:

FVC AUC0-4 at Day 29 [ Before drug administration to 4 hours after drug administration on Day 29 ]

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39. Secondary:

FVC AUC0-4 at Day 57 [ Before drug administration to 4 hours after drug administration on Day 57 ]

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40. Secondary:

FVC AUC0-4 at Day 85 [ Before drug administration to 4 hours after drug administration on Day 85 ]

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41. Secondary:

FVC AUC4-6 at Day 1 [ Between 4 hours and 6 hours after drug administration on Day 1 ]

Hide Outcome Measure 41

Measure Type	Secondary
Measure Title	FVC AUC4-6 at Day 1
Measure Description	Area between the test-day baseline FVC and the FVC change from the test-day baseline curve from 4 to 6 hours divided by 2 at Day 1
Time Frame	Between 4 hours and 6 hours after drug administration on Day 1
Safety Issue

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.
Full Analysis Set for Pulmonary Function Test Data 4-6 hours

Reporting Groups

	Description
COMBIVENT Respimat 20/100 Mcg	No text entered.
COMBIVENT CFC-MDI 36/206 Mcg	No text entered.
Ipratropium Respimat 20 Mcg	No text entered.

Measured Values

	COMBIVENT Respimat 20/100 Mcg	COMBIVENT CFC-MDI 36/206 Mcg	Ipratropium Respimat 20 Mcg
Number of Participants Analyzed [units: participants]	447	449	427
FVC AUC4-6 at Day 1 [units: liters] Least Squares Mean ± Standard Error	0.2 ± 0.017	0.221 ± 0.017	0.156 ± 0.018

Statistical Analysis 1 for FVC AUC4-6 at Day 1

Groups ^[1]	COMBIVENT Respimat 20/100 Mcg vs. Ipratropium Respimat 20 Mcg
Non-Inferiority/Equivalence Test ^[2]	Yes
Method ^[3]	ANCOVA
P Value ^[4]	0.0688
Mean Difference (Final Values) ^[5]	0.043
Standard Error of the mean	± 0.024
95% Confidence Interval	( -0.003 to 0.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	This analysis is purely exploratory. Non-inferiority margin is not established.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
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42. Secondary:

FVC AUC4-6 at Day 29 [ Between 4 hours and 6 hours after drug administration on Day 29 ]

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43. Secondary:

FVC AUC4-6 at Day 57 [ Between 4 hours and 6 hours after drug administration on Day 57 ]

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44. Secondary:

FVC AUC4-6 at Day 85 [ Between 4 hours and 6 hours after drug administration on Day 85 ]

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45. Secondary:

Peak FVC Response at Day 1 [ Within the first 2-hour post-treatment interval at Day 1 ]

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46. Secondary:

Peak FVC Response at Day 29 [ Within the first 2-hour post-treatment interval at Day 29 ]

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47. Secondary:

Peak FVC Response at Day 57 [ Within the first 2-hour post-treatment interval at Day 57 ]

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48. Secondary:

Peak FVC Response at Day 85 [ Within the first 2-hour post-treatment interval at Day 85 ]

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49. Secondary:

Peak FVC Response at Day 1 [ Within the first 2-hour post-treatment interval at Day 1 ]

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50. Secondary:

Peak FVC Response at Day 29 [ Within the first 2-hour post-treatment interval at Day 29 ]

Show Outcome Measure 50

51. Secondary:

Peak FVC Response at Day 57 [ Within the first 2-hour post-treatment interval at Day 57 ]

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52. Secondary:

Peak FVC Response at Day 85 [ Within the first 2-hour post-treatment interval at Day 85 ]

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53. Secondary:

Rescue Medication Use on Pulmonary Test Day 1 [ During the 6-hour pulmonary function testing after drug administration on Day 1 ]

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54. Secondary:

Rescue Medication Use on Pulmonary Test Day 29 [ During the 6-hour pulmonary function testing after drug administration on Day 29 ]

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55. Secondary:

Rescue Medication Use on Pulmonary Test Day 57 [ During the 6-hour pulmonary function testing after drug administration on Day 57 ]

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56. Secondary:

Rescue Medication Use on Pulmonary Test Day 85 [ During the 6-hour pulmonary function testing after drug administration on Day 85 ]

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57. Secondary:

Night-time Rescue Medication Use [ During the 2-week baseline washout period and the 12-week treatment period ]

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58. Secondary:

Night-time Rescue Medication Use [ During the 2-week baseline washout period and the 12-week treatment period ]

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59. Secondary:

Daytime Rescue Medication Use [ During the 2-week baseline washout period and the 12-week treatment period ]

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60. Secondary:

Daytime Rescue Medication Use [ During the 2-week baseline washout period and the 12-week treatment period ]

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61. Secondary:

Night-time Symptom Score [ During the 2-week baseline washout period and the 12-week treatment period ]

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62. Secondary:

Night-time Symptom Score [ During the 2-week baseline washout period and the 12-week treatment period ]

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63. Secondary:

Daytime Symptom Score [ During the 2-week baseline washout period and the 12-week treatment period ]

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64. Secondary:

Daytime Symptom Score [ During the 2-week baseline washout period and the 12-week treatment period ]

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65. Secondary:

Trough Peak Expiratory Flow Rate (PEFR) [ During the 2-week baseline washout period and the 12-week treatment period and PEFR taken before administration of study medication ]

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66. Secondary:

Trough PEFR [ During the 2-week baseline washout period and the 12-week treatment period and PEFR taken before administration of study medication ]

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67. Secondary:

Physician's Global Evaluation Score on Pulmonary Function Testing Day 29 [ Prior to pulmonary function test on Day 29 ]

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68. Secondary:

Physician's Global Evaluation Score on Pulmonary Function Testing Day 57 [ Prior to pulmonary function test on Day 57 ]

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69. Secondary:

Physician's Global Evaluation Score on Pulmonary Function Testing Day 85 [ Prior to pulmonary function test on Day 85 ]

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70. Secondary:

Physician's Global Evaluation Score on Pulmonary Function Testing Day 29 [ Prior to pulmonary function test on Day 29 ]

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71. Secondary:

Physician's Global Evaluation Score on Pulmonary Function Testing Day 57 [ Prior to pulmonary function test on Day 57 ]

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72. Secondary:

Physician's Global Evaluation Score on Pulmonary Function Testing Day 85 [ Prior to pulmonary function test on Day 85 ]

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73. Secondary:

Chronic Obstructive Pulmonary Disease (COPD) Excerbation During the On-treatment Period [ During the 12-week on-treatment period ]

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74. Secondary:

COPD Excerbation During the On-treatment Period [ During the 12-week on-treatment period ]

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75. Secondary:

COPD Excerbation During the On-treatment Period [ During the 12-week on-treatment period ]

Show Outcome Measure 75

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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.

Limitations and Caveats

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
The FEV1 and FVC measurements at each observation time point were used to derive the primary and secondary efficacy endpoints and are not reported here. All statistical analyses for secondary endpoints are exploratory and the p-values are nominal.

Results Point of Contact:

Name/Title: Boehringer Ingelheim Pharmaceuticals
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 800-542-6257 Option 4
e-mail: clintriage.rdg@boehringer-ingelheim.com

No publications provided

Responsible Party:	Boehringer Ingelheim ( Boehringer Ingelheim, Study Chair )
Study ID Numbers:	1012.56
Study First Received:	November 15, 2006
Results First Received:	April 3, 2009
Last Updated:	July 13, 2009
ClinicalTrials.gov Identifier:	NCT00400153 History of Changes
Health Authority:	Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products; Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow; Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine); New Zealand: Multicentre Ethics Committee/Medsafe; United States: Food and Drug Administration; France: AFSSAPS; Greece: National Organization for Medicines (EOF) National Ethics Committee; Argentina: A.N.M.A.T. (Administración Nacional de Medicamentos, Alimentos y Tecnología); Taiwan: Department of Health, Executive Yuan, Taiwan; Korea, Republic of: Korea Food and Drug Administration; Turkey: Ministry of Health Central Ethics Committee; Great Britain: MHRA; South Africa: MCC (Medicines Control Council)