Co-administration of Olodaterol Respimat® and Tiotropium Handihaler®

Phase 3

Completed

Conditions: Pulmonary Disease, Chronic Obstructive

Interventions: Drug: Tiotropium
Drug: Placebo matching Olodaterol
Drug: Olodaterol

Registration Number: NCT01696058

Lead Sponsor: Boehringer Ingelheim

Brief Summary: The overall objective of this study is to assess efficacy and safety of 12 weeks, once daily, orally inhaled co-administration of olodaterol 5 µg (delivered by the Respimat® Inhaler) and tiotropium (delivered by the Handihaler® as Spiriva Handihaler®), compared to tiotropium (Spiriva Handihaler®) monotherapy on lung function in patients with COPD.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1137

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo and Tiotropium	Placebo matching Olodaterol	2 puffs placebo inhalation solution from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
Olodaterol andTiotropium	Tiotropium	2 puffs Olodaterol from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
Olodaterol andTiotropium	Olodaterol	2 puffs Olodaterol from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
Placebo and Tiotropium	Tiotropium	2 puffs placebo inhalation solution from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered

Primary Outcome Measures

Name	Time	Method
FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12	baseline and 12 weeks	FEV1 (Forced expiratory volume in 1 second) AUC0-3h (area under the curve) response at 12 weeks; defined as change from baseline to Week 12. AUC was standardized by dividing by time unit.
Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12	baseline and 12 weeks	Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12

Secondary Outcome Measures

Name	Time	Method
Trough FVC Response at 12 Weeks; Defined as Change From Baseline	baseline and 12 weeks	Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline.
Rescue Medication Usage - Percentage of Rescue Free Days	over 12 weeks	Rescue medication usage - the percentage of rescue free days. The percentage of rescue free days is defined as: number of rescue free days divided by total exposure, multiplied by 100%. The baseline for the number of rescue-free days was defined as the number of rescue-free days observed during the last week of the baseline period (i.e., the 7 days prior to administration of the first dose of randomized treatment). Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline. Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (552)
Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)	over 12 weeks	Rescue medication usage - Mean weekly rescue usage during nighttime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary. Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline. Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)
Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)	over 12 weeks	Rescue medication usage - Mean weekly rescue usage during daytime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary. Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline. Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)
Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data	12 weeks	The Saint George Respiratory Questionnaire (SGRQ) is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It is divided into two parts. Part I produces the Symptoms score (several scales), and Part II the Activity and Impacts scores \[dichotomous (true/false) except last question (4-point Likert scale)\]. A Total score is also produced with scores ranging from 0 to 100, with higher scores indicating more limitations. Since the SGRQ analysis is based on the combined data from both this study and protocol 1222.51 (NCT01694771), only combined SGRQ results will be included in the latest clinical trial report. Hence there will only be one SGRQ analysis from both studies, which will not appear in the first clinical trial report. For this same reason, another covariate - study - will also be included in the MMRM for SGRQ analysis. The combined data for this outcome measure was pre-specified in both protocols.
Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)	over 12 weeks	Rescue medication usage - mean weekly rescue usage (total daily). The baseline for the rescue use was the mean of the observations during the last week of the baseline period. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol metered dose inhaler (MDI) (100 μg per puff) was provided as rescue medication . Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary. Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline. Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)
Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline	baseline and 12 weeks	Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as change from baseline. All p-values for these measures are only descriptive.
FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline	baseline and 12 Weeks	Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. AUC was standardized by dividing by time unit.
Peak FVC Response at 12 Weeks; Defined as Change From Baseline	baseline and 12 weeks	Peak FVC response at 12 weeks - defined as change from baseline.

Trial Locations

Locations (94): 1222.52.02068 Boehringer Ingelheim Investigational Site
🇺🇸
Chesterfield, Missouri, United States
1222.52.02035 Boehringer Ingelheim Investigational Site
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Henderson, Nevada, United States
1222.52.02091 Boehringer Ingelheim Investigational Site
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Syracuse, New York, United States
1222.52.02024 Boehringer Ingelheim Investigational Site
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O'Fallon, Illinois, United States
1222.52.02099 Boehringer Ingelheim Investigational Site
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Morgantown, West Virginia, United States
1222.52.02066 Boehringer Ingelheim Investigational Site
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Spartanburg, South Carolina, United States
1222.52.02095 Boehringer Ingelheim Investigational Site
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Spartanburg, South Carolina, United States
1222.52.02039 Boehringer Ingelheim Investigational Site
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Columbus, Ohio, United States
1222.52.02093 Boehringer Ingelheim Investigational Site
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Columbus, Ohio, United States
1222.52.02005 Boehringer Ingelheim Investigational Site
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Baltimore, Maryland, United States
1222.52.02029 Boehringer Ingelheim Investigational Site
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Columbia, Maryland, United States
1222.52.02028 Boehringer Ingelheim Investigational Site
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St. Louis, Missouri, United States
1222.52.02034 Boehringer Ingelheim Investigational Site
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North Dartmouth, Massachusetts, United States
1222.52.02048 Boehringer Ingelheim Investigational Site
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Duluth, Georgia, United States
1222.52.02014 Boehringer Ingelheim Investigational Site
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Mobile, Alabama, United States
1222.52.02009 Boehringer Ingelheim Investigational Site
🇺🇸
Blue Ridge, Georgia, United States
1222.52.02036 Boehringer Ingelheim Investigational Site
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Hollywood, Maryland, United States
1222.52.02092 Boehringer Ingelheim Investigational Site
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Anchorage, Alaska, United States
1222.52.02040 Boehringer Ingelheim Investigational Site
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Rincon, Georgia, United States
1222.52.02015 Boehringer Ingelheim Investigational Site
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Townson, Maryland, United States
1222.52.02079 Boehringer Ingelheim Investigational Site
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Plymouth, Minnesota, United States
1222.52.02077 Boehringer Ingelheim Investigational Site
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Gainsville, Georgia, United States
1222.52.02075 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1222.52.02057 Boehringer Ingelheim Investigational Site
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Midvale, Utah, United States
1222.52.02030 Boehringer Ingelheim Investigational Site
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Marlton, New Jersey, United States
1222.52.02026 Boehringer Ingelheim Investigational Site
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Medford, Oregon, United States
1222.52.02058 Boehringer Ingelheim Investigational Site
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Tabor City, North Carolina, United States
1222.52.02071 Boehringer Ingelheim Investigational Site
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Albuquerque, New Mexico, United States
1222.52.02097 Boehringer Ingelheim Investigational Site
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Medford, Oregon, United States
1222.52.02038 Boehringer Ingelheim Investigational Site
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Salisbury, North Carolina, United States
1222.52.02078 Boehringer Ingelheim Investigational Site
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Sugar Land, Texas, United States
1222.52.02082 Boehringer Ingelheim Investigational Site
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Waco, Texas, United States
1222.52.02056 Boehringer Ingelheim Investigational Site
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Houston, Texas, United States
1222.52.02090 Boehringer Ingelheim Investigational Site
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Anniston, Alabama, United States
1222.52.02017 Boehringer Ingelheim Investigational Site
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Montgomery, Alabama, United States
1222.52.02072 Boehringer Ingelheim Investigational Site
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Chandler, Arizona, United States
1222.52.02088 Boehringer Ingelheim Investigational Site
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Peoria, Arizona, United States
1222.52.02031 Boehringer Ingelheim Investigational Site
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San Jose, California, United States
1222.52.02006 Boehringer Ingelheim Investigational Site
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Huntington Beach, California, United States
1222.52.02011 Boehringer Ingelheim Investigational Site
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Torrance, California, United States
1222.52.02061 Boehringer Ingelheim Investigational Site
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Boulder, Colorado, United States
1222.52.02054 Boehringer Ingelheim Investigational Site
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Fort Collins, Colorado, United States
1222.52.02037 Boehringer Ingelheim Investigational Site
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Norwalk, Connecticut, United States
1222.52.02055 Boehringer Ingelheim Investigational Site
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Waterbury, Connecticut, United States
1222.52.02094 Boehringer Ingelheim Investigational Site
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Clearwater, Florida, United States
1222.52.02022 Boehringer Ingelheim Investigational Site
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Fort Lauderdale, Florida, United States
1222.52.02016 Boehringer Ingelheim Investigational Site
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Ponte Verda, Florida, United States
1222.52.02084 Boehringer Ingelheim Investigational Site
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St. Petersberg, Florida, United States
1222.52.02062 Boehringer Ingelheim Investigational Site
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Cincinnati, Ohio, United States
1222.52.02080 Boehringer Ingelheim Investigational Site
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Pittsburgh, Pennsylvania, United States
1222.52.02085 Boehringer Ingelheim Investigational Site
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Greenville, South Carolina, United States
1222.52.02101 Boehringer Ingelheim Investigational Site
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Greenville, South Carolina, United States
1222.52.02041 Boehringer Ingelheim Investigational Site
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El Paso, Texas, United States
1222.52.02012 Boehringer Ingelheim Investigational Site
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Phoenix, Arizona, United States
1222.52.02046 Boehringer Ingelheim Investigational Site
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Birmingham, Alabama, United States
1222.52.02047 Boehringer Ingelheim Investigational Site
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Minneapolis, Minnesota, United States
1222.52.02049 Boehringer Ingelheim Investigational Site
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Minneapolis, Minnesota, United States
1222.52.02059 Boehringer Ingelheim Investigational Site
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Oklahoma City, Oklahoma, United States
1222.52.02007 Boehringer Ingelheim Investigational Site
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San Antonio, Texas, United States
1222.52.02060 Boehringer Ingelheim Investigational Site
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San Antonio, Texas, United States
1222.52.02043 Boehringer Ingelheim Investigational Site
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Tampa, Florida, United States
1222.52.02053 Boehringer Ingelheim Investigational Site
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St. Louis, Missouri, United States
1222.52.02020 Boehringer Ingelheim Investigational Site
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Kalamazoo, Michigan, United States
1222.52.02002 Boehringer Ingelheim Investigational Site
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Muncie, Indiana, United States
1222.52.02003 Boehringer Ingelheim Investigational Site
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Chelsea, Michigan, United States
1222.52.02076 Boehringer Ingelheim Investigational Site
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Calabash, North Carolina, United States
1222.52.02045 Boehringer Ingelheim Investigational Site
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Raleigh, North Carolina, United States
1222.52.02010 Boehringer Ingelheim Investigational Site
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Huntersville, North Carolina, United States
1222.52.02102 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1222.52.02013 Boehringer Ingelheim Investigational Site
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Winston Salem, North Carolina, United States
1222.52.02086 Boehringer Ingelheim Investigational Site
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Arlington, Texas, United States
1222.52.02027 Boehringer Ingelheim Investigational Site
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Fort Worth, Texas, United States
1222.52.02019 Boehringer Ingelheim Investigational Site
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Tacoma, Washington, United States
1222.52.02069 Boehringer Ingelheim Investigational Site
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Selah, Washington, United States
1222.52.02081 Boehringer Ingelheim Investigational Site
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Columbus, Ohio, United States
1222.52.02008 Boehringer Ingelheim Investigational Site
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Fort Mitchell, Kentucky, United States
1222.52.02063 Boehringer Ingelheim Investigational Site
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Glendale, Arizona, United States
1222.52.02065 Boehringer Ingelheim Investigational Site
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Hodges, South Carolina, United States
1222.52.02096 Boehringer Ingelheim Investigational Site
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Easley, South Carolina, United States
1222.52.02042 Boehringer Ingelheim Investigational Site
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Myrtle Beach, South Carolina, United States
1222.52.02083 Boehringer Ingelheim Investigational Site
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Rock Hill, South Carolina, United States
1222.52.02098 Boehringer Ingelheim Investigational Site
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Union, South Carolina, United States
1222.52.02001 Boehringer Ingelheim Investigational Site
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Hartford, Connecticut, United States
1222.52.02050 Boehringer Ingelheim Investigational Site
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Billings, Montana, United States
1222.52.02018 Boehringer Ingelheim Investigational Site
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Brentwood, Tennessee, United States
1222.52.02074 Boehringer Ingelheim Investigational Site
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Orlando, Florida, United States
1222.52.02025 Boehringer Ingelheim Investigational Site
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Louisville, Kentucky, United States
1222.52.02089 Boehringer Ingelheim Investigational Site
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New Orleans, Louisiana, United States
1222.52.02044 Boehringer Ingelheim Investigational Site
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Austin, Texas, United States
1222.52.02100 Boehringer Ingelheim Investigational Site
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Charleston, South Carolina, United States
1222.52.02023 Boehringer Ingelheim Investigational Site
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Richmond, Virginia, United States
1222.52.02064 Boehringer Ingelheim Investigational Site
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Johnson City, New York, United States
1222.52.02087 Boehringer Ingelheim Investigational Site
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New Windsor, New York, United States
1222.52.02051 Boehringer Ingelheim Investigational Site
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Shelby, North Carolina, United States