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Co-administration of Olodaterol Respimat® and Tiotropium Handihaler®

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01696058
First received: September 26, 2012
Last updated: November 13, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium
Drug: Placebo matching Olodaterol
Drug: Olodaterol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Double Blind, Parallel Group Study to Assess the Efficacy and Safety of 12 Weeks of Once Daily, Orally Inhaled, Co-administration of Olodaterol 5µg (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) Compared to Once Daily, Orally Inhaled, Co-administration of Placebo (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) in Patients With Chronic Obstructive Pulmonary Disease (COPD)[ANHELTO TM 2]

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12 [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12


Secondary Outcome Measures:
  • Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 12 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Peak FVC response at 12 weeks - defined as change from baseline.

  • Trough FVC Response at 12 Weeks; Defined as Change From Baseline [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline.

  • Rescue Medication Usage - Percentage of Rescue Free Days [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]

    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 (Total Daily) [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]

    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)


  • Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime) [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]

    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)


  • Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime) [ Time Frame: over 12 weeks ] [ Designated as safety issue: No ]

    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)



Enrollment: 1137
Study Start Date: September 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olodaterol andTiotropium
2 puffs Olodaterol from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
Drug: Tiotropium
marketed product
Drug: Olodaterol
one dose
Placebo and Tiotropium
2 puffs placebo inhalation solution from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
Drug: Tiotropium
marketed product
Drug: Placebo matching Olodaterol
one dose

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. All patients must sign an informed consent consistent with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which includes medication washout and restrictions.
  2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: Patients must have a relatively stable airway obstruction with a post-bronchodilator FEV1 ≥ 30 % and < 80% of predicted normal and a post-bronchodilator FEV1/FVC <70% at Visit 1.
  3. Male or female patients, 40 years of age or older.
  4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years
  5. Patients must be able to: perform technically acceptable pulmonary function tests, and maintain records(paper diary).
  6. Patients must be able to inhale medication in a competent manner from the Respimat Inhaler as well as the Handihaler.

Exclusion criteria:

  1. Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patients ability to participate in the study.
  2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an AST >x2 ULN, ALT >x2 ULN, bilirubin >x2 ULN or creatinine >x2 ULN will be excluded regardless of clinical condition (a repeat laboratory evaluation will not be conducted in these patients).
  3. Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. If a patient has a total blood eosinophil count ≥600/mm3, source documentation is required to verify that the increased eosinophil count is related to a non-asthmatic condition.
  4. A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists).
  5. A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class side effect profile of ß2-agonists).
  6. A history of myocardial infarction within 1 year of screening visit (Visit 1).
  7. Unstable or life-threatening cardiac arrhythmia.
  8. Hospitalization for heart failure within the past year.
  9. Known active tuberculosis.
  10. A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed).
  11. A history of life-threatening pulmonary obstruction.
  12. A history of cystic fibrosis.
  13. Clinically evident bronchiectasis.
  14. A history of significant alcohol or drug abuse.
  15. Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1).
  16. Patients being treated with oral or patch ß-adrenergics.
  17. Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
  18. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigators opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
  19. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program.
  20. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit (Visit 1).
  21. Patients with known hypersensitivity to ß-adrenergic drugs, BAC, EDTA, or any other component of the Respimat® inhalation solution.
  22. Patients with known hypersensitivity to anticholinergic drugs, lactose, or any other components of the HandiHaler®.
  23. Pregnant or nursing women.
  24. Women of childbearing potential not using a highly effective method of birth control*. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.

    * as per ICH M3(R2) a highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year).

  25. Patients who have previously been randomised in this study or are currently participating in another study.
  26. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01696058

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

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01696058     History of Changes
Other Study ID Numbers: 1222.52
Study First Received: September 26, 2012
Results First Received: September 5, 2014
Last Updated: November 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Tiotropium
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014