Characterization of 24 Hour Spirometry Profiles of Inhale... | NCT00931385

NCT00931385

Status Module

Sponsor/Collaborators Module

Oversight Module

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No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BI 1744 (Olodaterol) Low Dose	Experimental	BI1744 Low Dose once daily	Drug: bi1744
BI 1744 (Olodaterol) Med Dose	Experimental	BI 1744 Med Dose once daily	Drug: BI 1744
Placebo	Placebo Comparator	Placebo once daily	Drug: Placebo
Foradil	Active Comparator	Foradil 12 mcg twice daily	Drug: Foradil

Name	Type	Description	Arm Group Labels	Other Names
BI 1744	Drug	BI1744 Respimat Med Dose Once Daily	BI 1744 (Olodaterol) Med Dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
FEV1 Area Under Curve 0-12 h (AUC 0-12h) Response After Six Weeks of Treatment	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.	1 hour (h) and 10 minutes (min) prior to am dose on the first day of treatment (baseline) and -30 min (zero time), 30 min, 60 min, 2 hour (h) , 3 h, 4 h, 6 h, 8 h, 10 h, 11 h 50 min relative to am dose after six weeks of treatment
FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.	1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

Secondary Outcomes

Measure	Description	Time Frame
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1222.24.24011 Boehringer Ingelheim Investigational Site		Tampa	Florida		United States
1222.24.24009 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25187881	Derived	Feldman GJ, Bernstein JA, Hamilton A, Nivens MC, Korducki L, LaForce C. The 24-h FEV1 time profile of olodaterol once daily via Respimat(R) and formoterol twice daily via Aerolizer(R) in patients with GOLD 2-4 COPD: results from two 6-week crossover studies. Springerplus. 2014 Aug 9;3:419. doi: 10.1186/2193-1801-3-419. eCollection 2014.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Olo 5mcg / Foradil 12mcg / Placebo / Olo 10mcg	Patients were administered Olodaterol 5 mcg qd in the first period, Foradil 12 mcg bid in the second period, matching Placebo in the third period and Olodaterol 10 mcg qd in the fourth period. Olodaterol was administered via the Respimat inhaler, Foradil was administered via the Aerolizer inhaler.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

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No data is available for this block.

Document Section

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Derived Section

Miscellaneous Info Module

Submission Tracking

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No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Treated set, i.e., all treated patients.

Arm/Group Information

ID	Title	Description
BG000	Study Total	Total number of patients treated in the study. This was a randomised, double-blind, double dummy, placebo- and active-controlled, 4 way crossover trial. 99 patients were assigned randomly to one of 4 treatment sequences in which they received each of 4 treatments, two doses (5 microgram (mcg) or 10 mcg) of Olodaterol (Olo) once daily (qd) delivered via the Respimat inhaler or Foradil (Form) 12 mcg twice daily (bid) delivered via the Aerolizer inhaler or equivalent placebo delivered by Respimat Inhaler or Aerolizer Inhaler. The duration of each treatment period was 6 weeks with a 14 day washout period between treatments.

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000-0.060± 0.020 OG0010.088± 0.021 OG0020.088± 0.021 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	Adjusted using a mixed model with center, treatment and period as fixed effects and patients within center as random effect.	<0.0001		Mean Difference (Final Values)	0.148	Standard Error of the Mean	0.018		95	0.113	0.183			Olo 5 mcg qd minus Placebo	No	Superiority or Other

Primary

FEV1 Area Under Curve 12-24h (AUC 12-24h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed in the morning of the first treatment visit, just prior to administration of the morning dose of randomized treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 12-24h was calculated from 12-24 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

FAS

Posted

Least Squares Mean

Standard Error

Liter

1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.

Secondary

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-24 h (AUC 0-24h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.FEV1 AUC 0-24h was calculated from 0-24 hours post-dose using the trapezoidal rule, divided by the observation time (24h) to report in litres.

FAS

Posted

Least Squares Mean

Standard Error

Liter

1 h and 10 min prior to am dose on the first day of treatment (baseline) and -30 min, 30 min, 60 min, 2h, 3h, 4h, 6h, 8h, 10h, 11 hr 50 min,12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment.

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.

Secondary

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response After Six Weeks of Treatment

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FEV1 AUC 0-3h was calculated from 0-3hours post-dose using the trapezoidal rule, divided by the observation time (3 h) to report in litres.

FAS

Posted

Least Squares Mean

Standard Error

Liter

1 hour (h) prior and 10 minutes (min) prior to first dose (baseline) and -30 min, 30 min, 60 min, 2 h , 3 h, relative to the last am dose after six weeks of treatment

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003

Secondary

Peak FEV1 (0-3h) Response

Response was defined as change from baseline. Study baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values at the randomisation visit. Peak (0-3h) values were obtained within 0 - 3 hours after the last am dose after six weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

FAS

Posted

Least Squares Mean

Standard Error

Liter

Baseline and 6 weeks

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003	Form 12 mcg Bid	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.

Secondary

Trough FEV1 Response

Response was defined as change from baseline. Study baseline trough FEV1 was defined as the mean of the available pre-dose trough FEV1 values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

FAS

Posted

Least Squares Mean

Standard Error

Liter

Baseline and 6 weeks

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003	Form 12 mcg Bid	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.

Secondary

Forced Vital Capacity (FVC) Area Under Curve 0-12 Hours (AUC 0-12h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-12h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

FAS

Posted

Least Squares Mean

Standard Error

Liter

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003

Secondary

FVC Area Under Curve 12-24 Hours (AUC 12-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 12-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

FAS

Posted

Least Squares Mean

Standard Error

Liter

1 h and 10 min prior to am dose on the first day of treatment (baseline) and 12 h 30 min, 13 h, 14 h, 22 h, 23 h, and 23 h 50 min relative to am dose after six weeks of treatment

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003	Form 12 mcg Bid

Secondary

FVC Area Under Curve 0-24 Hours (AUC 0-24h) Response

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values at the randomisation visit. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random. FVC AUC 0-24h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

FAS

Posted

Least Squares Mean

Standard Error

Liter

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003	Form 12 mcg Bid

Secondary

Peak FVC (0-3h) Response

Response was defined as change from baseline. Study baseline peak FVC was defined as the mean of the available pre-dose peak FVC values at the randomisation visit. Peak FVC (0-3h) was obtained within 0 - 3 hours after the last am dose of study drug after 6 weeks of treatment. Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

FAS

Posted

Least Squares Mean

Standard Error

Liter

Baseline and 6 weeks

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003	Form 12 mcg Bid	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.

Secondary

Trough FVC Response

Response was defined as change from baseline. Study baseline trough FVC was defined as the mean of the available pre-dose trough FVC values at the randomisation visit. Trough values were obtained 30 minutes prior to the last am dose of study drug after six weeks of treatment . Means are adjusted using a mixed effects model with center, treatment and period as fixed effects and patient within center as random.

FAS

Posted

Least Squares Mean

Standard Error

Liter

Baseline and 6 weeks

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg qd	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg qd	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003	Form 12 mcg Bid	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.

Secondary

Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG

Clinical relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis and ECG. New abnormal findings or worsenings of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations).

Treated set.

Posted

Number

participants

6 weeks

ID	Title	Description
OG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.
OG001	Olo 5 mcg	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.
OG002	Olo 10 mcg	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
OG003	Form 12 mcg	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Matching Placebo delivered by the Respimat resp. Aerolizer Inhaler.	4	96	5	96
EG001	Olo 5 mcg	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	4	95	4	95
EG002	Olo 10 mcg	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	2	92	1	92
EG003	Form 12 mcg	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	1	93	3	93

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected96 at risk EG0010 affected95 at risk EG0020 affected92 at risk EG0030 affected93 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected96 at risk EG0011 affected95 at risk EG0020 affected92 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0021 affected92 at risk EG003
Pneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected96 at risk EG0011 affected95 at risk EG0020 affected92 at risk EG003
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0021 affected92 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected96 at risk EG0010 affected95 at risk EG0020 affected92 at risk EG003
Radiculopathy	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0021 affected92 at risk EG003
Depression	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected96 at risk EG0011 affected95 at risk EG0020 affected92 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected96 at risk EG0011 affected95 at risk EG0020 affected92 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment		EG0005 affected96 at risk EG0014 affected95 at risk EG0021 affected92 at risk EG0033 affected93 at risk

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive

Ancestor Terms

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C549647	olodaterol
D000068759	Formoterol Fumarate

Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.

Units	Counts
Participants	OG00096 OG00195 OG00292 OG00393

ID	Term
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines