Co-administration of Olodaterol Respimat® and Tiotropium Handihaler®

August 25, 2014 updated by: Boehringer Ingelheim

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 1]

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1134

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Florence, Alabama, United States
        • 1222.51.01055 Boehringer Ingelheim Investigational Site
      • Jasper, Alabama, United States
        • 1222.51.01087 Boehringer Ingelheim Investigational Site
    • Arizona
      • Phoenix, Arizona, United States
        • 1222.51.01066 Boehringer Ingelheim Investigational Site
      • Scottsdale, Arizona, United States
        • 1222.51.01069 Boehringer Ingelheim Investigational Site
    • California
      • Anaheim, California, United States
        • 1222.51.01040 Boehringer Ingelheim Investigational Site
      • Encinitas, California, United States
        • 1222.51.01064 Boehringer Ingelheim Investigational Site
      • Fullerton, California, United States
        • 1222.51.01060 Boehringer Ingelheim Investigational Site
      • Lincoln, California, United States
        • 1222.51.01084 Boehringer Ingelheim Investigational Site
      • San Diego, California, United States
        • 1222.51.01041 Boehringer Ingelheim Investigational Site
      • San Diego, California, United States
        • 1222.51.01094 Boehringer Ingelheim Investigational Site
      • Torrance, California, United States
        • 1222.51.01015 Boehringer Ingelheim Investigational Site
    • Colorado
      • Boulder, Colorado, United States
        • 1222.51.01052 Boehringer Ingelheim Investigational Site
      • Wheat Ridge, Colorado, United States
        • 1222.51.01010 Boehringer Ingelheim Investigational Site
      • Wheat Ridge, Colorado, United States
        • 1222.51.01042 Boehringer Ingelheim Investigational Site
    • Connecticut
      • Stamford, Connecticut, United States
        • 1222.51.01070 Boehringer Ingelheim Investigational Site
    • Florida
      • Clearwater, Florida, United States
        • 1222.51.01006 Boehringer Ingelheim Investigational Site
      • Clearwater, Florida, United States
        • 1222.51.01021 Boehringer Ingelheim Investigational Site
      • Clearwater, Florida, United States
        • 1222.51.01082 Boehringer Ingelheim Investigational Site
      • DeLand, Florida, United States
        • 1222.51.01065 Boehringer Ingelheim Investigational Site
      • Jacksonville, Florida, United States
        • 1222.51.01051 Boehringer Ingelheim Investigational Site
      • Jacksonville, Florida, United States
        • 1222.51.01092 Boehringer Ingelheim Investigational Site
      • Ormond Beach, Florida, United States
        • 1222.51.01081 Boehringer Ingelheim Investigational Site
      • Panama City, Florida, United States
        • 1222.51.01054 Boehringer Ingelheim Investigational Site
      • Pensacola, Florida, United States
        • 1222.51.01062 Boehringer Ingelheim Investigational Site
      • Port Orange, Florida, United States
        • 1222.51.01088 Boehringer Ingelheim Investigational Site
      • Tamarac, Florida, United States
        • 1222.51.01079 Boehringer Ingelheim Investigational Site
    • Georgia
      • Atlanta, Georgia, United States
        • 1222.51.01075 Boehringer Ingelheim Investigational Site
      • Austell, Georgia, United States
        • 1222.51.01076 Boehringer Ingelheim Investigational Site
      • Duluth, Georgia, United States
        • 1222.51.01057 Boehringer Ingelheim Investigational Site
      • Lawrenceville, Georgia, United States
        • 1222.51.01086 Boehringer Ingelheim Investigational Site
    • Idaho
      • Coeur d'Alene, Idaho, United States
        • 1222.51.01019 Boehringer Ingelheim Investigational Site
      • Eagle, Idaho, United States
        • 1222.51.01027 Boehringer Ingelheim Investigational Site
    • Illinois
      • Arlingron Heights, Illinois, United States
        • 1222.51.01048 Boehringer Ingelheim Investigational Site
      • River Forest, Illinois, United States
        • 1222.51.01044 Boehringer Ingelheim Investigational Site
      • Skokie, Illinois, United States
        • 1222.51.01043 Boehringer Ingelheim Investigational Site
    • Kentucky
      • Louisville, Kentucky, United States
        • 1222.51.01090 Boehringer Ingelheim Investigational Site
    • Louisiana
      • Lafayette, Louisiana, United States
        • 1222.51.01023 Boehringer Ingelheim Investigational Site
      • Opelousas, Louisiana, United States
        • 1222.51.01071 Boehringer Ingelheim Investigational Site
    • Massachusetts
      • North Dartmouth, Massachusetts, United States
        • 1222.51.01050 Boehringer Ingelheim Investigational Site
    • Michigan
      • Ann Arbor, Michigan, United States
        • 1222.51.01049 Boehringer Ingelheim Investigational Site
      • Livonia, Michigan, United States
        • 1222.51.01025 Boehringer Ingelheim Investigational Site
    • Minnesota
      • Edina, Minnesota, United States
        • 1222.51.01078 Boehringer Ingelheim Investigational Site
      • Fridley, Minnesota, United States
        • 1222.51.01033 Boehringer Ingelheim Investigational Site
    • Missouri
      • St. Charles, Missouri, United States
        • 1222.51.01074 Boehringer Ingelheim Investigational Site
      • St. Louis, Missouri, United States
        • 1222.51.01037 Boehringer Ingelheim Investigational Site
    • Nevada
      • Reno, Nevada, United States
        • 1222.51.01039 Boehringer Ingelheim Investigational Site
    • New York
      • Larchmont, New York, United States
        • 1222.51.01045 Boehringer Ingelheim Investigational Site
      • Rochester, New York, United States
        • 1222.51.01018 Boehringer Ingelheim Investigational Site
    • North Carolina
      • Asheville, North Carolina, United States
        • 1222.51.01014 Boehringer Ingelheim Investigational Site
      • Charlotte, North Carolina, United States
        • 1222.51.01077 Boehringer Ingelheim Investigational Site
      • Greensboro, North Carolina, United States
        • 1222.51.01056 Boehringer Ingelheim Investigational Site
    • Ohio
      • Canton, Ohio, United States
        • 1222.51.01032 Boehringer Ingelheim Investigational Site
      • Cincinnati, Ohio, United States
        • 1222.51.01011 Boehringer Ingelheim Investigational Site
      • Columbus, Ohio, United States
        • 1222.51.01005 Boehringer Ingelheim Investigational Site
      • Dayton, Ohio, United States
        • 1222.51.01093 Boehringer Ingelheim Investigational Site
      • Sylvania, Ohio, United States
        • 1222.51.01089 Boehringer Ingelheim Investigational Site
      • Toledo, Ohio, United States
        • 1222.51.01080 Boehringer Ingelheim Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • 1222.51.01017 Boehringer Ingelheim Investigational Site
      • Tulsa, Oklahoma, United States
        • 1222.51.01047 Boehringer Ingelheim Investigational Site
    • Oregon
      • Corvallis, Oregon, United States
        • 1222.51.01031 Boehringer Ingelheim Investigational Site
      • Medford, Oregon, United States
        • 1222.51.01020 Boehringer Ingelheim Investigational Site
      • Portland, Oregon, United States
        • 1222.51.01053 Boehringer Ingelheim Investigational Site
    • Pennsylvania
      • Erie, Pennsylvania, United States
        • 1222.51.01016 Boehringer Ingelheim Investigational Site
      • Philadelphia, Pennsylvania, United States
        • 1222.51.01004 Boehringer Ingelheim Investigational Site
    • Rhode Island
      • East Providence, Rhode Island, United States
        • 1222.51.01030 Boehringer Ingelheim Investigational Site
      • Johnston, Rhode Island, United States
        • 1222.51.01009 Boehringer Ingelheim Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States
        • 1222.51.01036 Boehringer Ingelheim Investigational Site
      • Columbia, South Carolina, United States
        • 1222.51.01061 Boehringer Ingelheim Investigational Site
      • Easley, South Carolina, United States
        • 1222.51.01038 Boehringer Ingelheim Investigational Site
      • Easley, South Carolina, United States
        • 1222.51.01046 Boehringer Ingelheim Investigational Site
      • Gaffney, South Carolina, United States
        • 1222.51.01022 Boehringer Ingelheim Investigational Site
      • Greenville, South Carolina, United States
        • 1222.51.01063 Boehringer Ingelheim Investigational Site
      • Greer, South Carolina, United States
        • 1222.51.01013 Boehringer Ingelheim Investigational Site
      • Spartanburg, South Carolina, United States
        • 1222.51.01024 Boehringer Ingelheim Investigational Site
      • Union, South Carolina, United States
        • 1222.51.01012 Boehringer Ingelheim Investigational Site
    • South Dakota
      • Rapid City, South Dakota, United States
        • 1222.51.01008 Boehringer Ingelheim Investigational Site
    • Tennessee
      • Johnson City, Tennessee, United States
        • 1222.51.01035 Boehringer Ingelheim Investigational Site
    • Texas
      • Boerne, Texas, United States
        • 1222.51.01028 Boehringer Ingelheim Investigational Site
      • Corsicana, Texas, United States
        • 1222.51.01083 Boehringer Ingelheim Investigational Site
      • Killeen, Texas, United States
        • 1222.51.01085 Boehringer Ingelheim Investigational Site
      • Longview, Texas, United States
        • 1222.51.01073 Boehringer Ingelheim Investigational Site
      • San Antonio, Texas, United States
        • 1222.51.01003 Boehringer Ingelheim Investigational Site
    • Utah
      • Murray, Utah, United States
        • 1222.51.01058 Boehringer Ingelheim Investigational Site
    • Virginia
      • Abingdon, Virginia, United States
        • 1222.51.01068 Boehringer Ingelheim Investigational Site
      • Richmond, Virginia, United States
        • 1222.51.01029 Boehringer Ingelheim Investigational Site
      • Richmond, Virginia, United States
        • 1222.51.01034 Boehringer Ingelheim Investigational Site
      • Richmond, Virginia, United States
        • 1222.51.01072 Boehringer Ingelheim Investigational Site
    • Washington
      • Spokane, Washington, United States
        • 1222.51.01091 Boehringer Ingelheim Investigational Site
      • Vancouver, Washington, United States
        • 1222.51.01002 Boehringer Ingelheim Investigational Site
    • West Virginia
      • Morgantown, West Virginia, United States
        • 1222.51.01001 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Olodaterol and Tiotropium
2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered
Drug: Tiotropium
Marketed dose
Drug: Olodaterol
One dose
Other: Placebo and Tiotropium
2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered
Drug: Tiotropium
Marketed dose
Drug: Placebo matching Olodaterol
One dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12
Time Frame: 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
baseline and 12 weeks
Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12
Time Frame: baseline and 12 weeks
Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12
baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline
Time Frame: baseline and 12 weeks
Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as changes from baseline
baseline and 12 weeks
FVC AUC0-3h Response at 12 Weeks - Defined as Change From Baseline
Time Frame: baseline and 12 weeks
Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline.
baseline and 12 weeks
Trough FVC Response at 12 Weeks- Defined as Change From Baseline
Time Frame: baseline and 12 weeks
Trough Forced Vital Capacity (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
Time Frame: baseline and 12 weeks
Peak FVC response at 12 weeks - defined as change from baseline.
baseline and 12 weeks
Rescue Medication Usage - Percentage of Rescue Free Days
Time Frame: 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).
over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)
Time Frame: 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 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.
over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)
Time Frame: 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.
over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)
Time Frame: 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.
over 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

September 25, 2012

First Submitted That Met QC Criteria

September 25, 2012

First Posted (Estimate)

September 27, 2012

Study Record Updates

Last Update Posted (Estimate)

September 4, 2014

Last Update Submitted That Met QC Criteria

August 25, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1222.51

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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