Efficacy Safety Study of Arformoterol/Tiotropium Combination Versus Either Therapy Alone in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Sunovion

ClinicalTrials.gov Identifier:

NCT00424528

First received: January 17, 2007

Last updated: May 29, 2012

Last verified: May 2012

History of Changes

Results First Received: October 24, 2008

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator); Primary Purpose: Treatment
Conditions:	Chronic Obstructive Pulmonary Disease Bronchitis Emphysema
Interventions:	Drug: Arformoterol Tartrate Inhalation Solution Drug: Tiotropium Drug: Arformoterol and Tiotropium Drug: Placebo

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
Multicenter (34 sites) study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Started: consists of all subjects who were randomized to treatment and received at least one dose of randomized study drug (Intent to treat population). One patient was randomized to the arformoterol/tiotropium group but discontinued before receiving any study medication and is therefore not included.

Reporting Groups

	Description
Arformoterol 15 Mcg Twice Daily	Arformoterol 15 mcg twice daily/Placebo Inhalation Powder
Tiotropium 18 Mcg Once Daily	Tiotropium 18 mcg once daily/Placebo Inhalation Solution
Arformoterol /Tiotropium	Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily

Participant Flow: Overall Study

	Arformoterol 15 Mcg Twice Daily	Tiotropium 18 Mcg Once Daily	Arformoterol /Tiotropium
STARTED	76	80	78
COMPLETED	71	76	74
NOT COMPLETED	5	4	4
Adverse Event	2	1	2
Protocol Violation	1	1	0
Lost to Follow-up	0	1	0
noncompliance with study requirements	2	1	2

Baseline Characteristics

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Reporting Groups

	Description
Arformoterol 15 Mcg Twice Daily	Arformoterol 15 mcg twice daily/Placebo Inhalation Powder
Tiotropium 18 Mcg Once Daily	Tiotropium 18 mcg once daily/Placebo Inhalation Solution
Arformoterol /Tiotropium	Arformoterol 15 mcg twice daily/Tiotropium 18 mcg once daily
Total	Total of all reporting groups

Baseline Measures

	Arformoterol 15 Mcg Twice Daily	Tiotropium 18 Mcg Once Daily	Arformoterol /Tiotropium	Total
Number of Participants [units: participants]	76	80	78	234
Age [units: participants]
<=18 years	0	0	0	0
Between 18 and 65 years	47	50	52	149
>=65 years	29	30	26	85
Age [units: years] Mean ± Standard Deviation	61.6 ± 8.4	61.2 ± 9.5	62.2 ± 7.6	61.7 ± 8.5
Gender [units: participants]
Female	37	37	36	110
Male	39	43	42	124
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	1	1
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	5	6	7	18
White	71	74	70	215
More than one race	0	0	0	0
Unknown or Not Reported	0	0	0	0
Region of Enrollment [units: participants]
United States	76	80	78	234
Number of Pack Years Smoked ^[1] [units: Participants]
>=15 years to <25 years	0	1	6	7
>=25 years to <=30 years	4	4	4	12
>=30 years	72	75	68	215
Packs per day currently smoked ^[2] [units: Participants]
>0 to 1 pack	24	30	22	76
>1 to 2 packs	22	24	16	62
>2 to 4 packs	3	0	1	4
>4 packs	0	0	0	0
Currently does not smoke	27	26	39	92
Baseline Dyspnea Index (BDI) Focal Score ^[3] [units: units on a scale] Mean ± Standard Deviation	5.8 ± 2.0	5.8 ± 1.9	5.5 ± 2.1	5.7 ± 2.0
Best Forced Expiratory Volume in one second (FEV1)/Best Forced Vital Capacity (FVC) ratio [units: Liters] Mean ± Standard Deviation	0.510 ± 0.098	0.514 ± 0.107	0.525 ± 0.108	0.516 ± 0.104
FEV1 [units: Liters] Mean ± Standard Deviation	1.366 ± 0.457	1.377 ± 0.460	1.350 ± 0.408	1.365 ± 0.440
FEV1 Percent Predicted [units: percent predicted of FEV1] Mean ± Standard Deviation	45.4 ± 11.9	45.7 ± 11.5	44.9 ± 12.0	45.4 ± 11.8
Inspiratory Capacity [units: Liters] Mean ± Standard Deviation	2.005 ± 0.615	1.979 ± 0.555	1.924 ± 0.516	1.969 ± 0.562
Modified Medical Research Council Dyspnea Questionnaire ^[4] [units: units on a scale] Mean ± Standard Deviation	2.7 ± 0.6	2.9 ± 0.7	2.9 ± 0.6	2.8 ± 0.6

[1]	Number of participants with a particular range of pack years smoked.
[2]	Number of participants with a particular range of packs per day currently smoked.
[3]	Baseline Dyspnea Index(range 0-12) is defined to be the sum of the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each on a 0-4 scale) obtained at visit 2 (baseline. On each scale, a high measurement represents the most impairment to health.
[4]	The Dyspnea scale score reflects the highest numbered question to which the subject answered "yes" in a series of five questions, each describing progressively worse dyspnea. Scores range from 0 to 4, with a score of 4 indicating that a subject is too breathless to leave the house or becomes breathless when dressing or undressing.

Outcome Measures

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1. Primary:

Time-normalized Area Under the Change From Study Baseline Curve for Forced Expiratory Volume in One Second (FEV1) Over 24 Hours (nAUC0-24B) [ Time Frame: 24 hours following two weeks of dosing. ]

Show Outcome Measure 1

2. Secondary:

Time-normalized Area From Study Baseline Curve for FEV1 Over 0-12 Hours (nAUC0-12B) [ Time Frame: 0-12 hours following two weeks of dosing ]

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3. Secondary:

Time Normalized Area Under the Change From Study Baseline Curve for FEV1 Over 12-24 Hours (nAUC12-24B) [ Time Frame: Following 2 weeks of dosing ]

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4. Secondary:

Change in FEV1 From Study Baseline to the 24-hour Timepoint (Trough) [ Time Frame: Following 2 weeks of dosing ]

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5. Secondary:

Change in FEV1 From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication [ Time Frame: 2 weeks ]

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6. Secondary:

Change in FEV1 Percent of Predicted From Study Baseline at Each Assessed Timepoint Post First Dose of Study Medication [ Time Frame: 2 weeks ]

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7. Secondary:

Peak Change in FEV1 Over 12 Hours Post Dose From Study Baseline [ Time Frame: 2 weeks ]

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8. Secondary:

Time to Onset in Participants Who Achieved a 10% Increase in FEV1 From Visit Predose After 2 Weeks [ Time Frame: 2 weeks ]

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9. Secondary:

Time to Onset in Participants Who Achieved a 15% Increase in FEV1 From Visit Predose After 2 Weeks [ Time Frame: 2 weeks ]

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10. Secondary:

Change in Inspiratory Capacity From Study Baseline to the 24 Hour Timepoint (Trough) Following 2 Weeks of Dosing [ Time Frame: 2 weeks ]

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11. Secondary:

Change in Forced Vital Capacity (FVC) From Study Baseline at Each Assessed Post Dose Timepoint [ Time Frame: 2 Weeks ]

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12. Secondary:

Levalbuterol Metered Dose Inhaler (MDI) (Rescue Medication) Use in Days Per Week [ Time Frame: 2 weeks ]

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13. Secondary:

Levalbuterol Metered Dose Inhaler (MDI) Rescue Medication Use in Actuations Per Day [ Time Frame: 2 weeks ]

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14. Secondary:

Transition Dyspnea Index (TDI) Focal Score [ Time Frame: 2 weeks ]

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15. Secondary:

Number of Participants With a >= 1 Unit of Improvement in the TDI Focal Score [ Time Frame: 2 weeks ]

Show Outcome Measure 15

16. Secondary:

Percentage of Participants With a >=1 Unit Improvement in Transition Dysnea Index (TDI) Focal Score [ Time Frame: 2 weeks ]

Show Outcome Measure 16

Serious Adverse Events

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Other Adverse Events

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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:

	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: In addition to the <60-180 day restriction above, since this is a multicenter study, 1st publication of study results shall be made with other participating study sites as a multicenter publication; provided, if a multicenter publication is not forthcoming within 24 months following completion of study at all sites, the PI shall be free to publish.

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
As of October 24, 2008, Sepracor is unaware of any limitations or caveats associated with this study.

Results Point of Contact:

Name/Title: Respiratory Medical Affairs Director
Organization: Sepracor Inc
phone: 866-503-6351

No publications provided by Sunovion

Publications automatically indexed to this study:

Tashkin DP, Donohue JF, Mahler DA, Huang H, Goodwin E, Schaefer K, Hanrahan JP, Andrews WT. Effects of arformoterol twice daily, tiotropium once daily, and their combination in patients with COPD. Respir Med. 2009 Apr;103(4):516-24. Epub 2009 Feb 8.

Responsible Party:	Sunovion
ClinicalTrials.gov Identifier:	NCT00424528 History of Changes
Other Study ID Numbers:	091-902
Study First Received:	January 17, 2007
Results First Received:	October 24, 2008
Last Updated:	May 29, 2012
Health Authority:	United States: Food and Drug Administration

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