Pulmonary Disease, Chronic ObstructivePhase 3NCT01696058

Co-administration of Olodaterol Respimat® and Tiotropium Handihaler®

A Phase 3 study testing Tiotropium and Olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 94 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: Tiotropium and Olodaterol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,137 participants
Where: 94 sitesUnited States
Study dates: Sep 2012to Oct 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.
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.
Male or female patients, 40 years of age or older.
Patients must be current or ex-smokers with a smoking history of more than 10 pack years
Patients must be able to: perform technically acceptable pulmonary function tests, and maintain records(paper diary).
Patients must be able to inhale medication in a competent manner from the Respimat Inhaler as well as the Handihaler.

Who cannot join

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.
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).
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.
A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists).
A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class side effect profile of ß2-agonists).
A history of myocardial infarction within 1 year of screening visit (Visit 1).

Show all 27Show fewer

Unstable or life-threatening cardiac arrhythmia.
Hospitalization for heart failure within the past year.
Known active tuberculosis.
A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed).
A history of life-threatening pulmonary obstruction.
A history of cystic fibrosis.
Clinically evident bronchiectasis.
A history of significant alcohol or drug abuse.
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).
Patients being treated with oral or patch ß-adrenergics.
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.
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.
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.
Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit (Visit 1).
Patients with known hypersensitivity to ß-adrenergic drugs, BAC, EDTA, or any other component of the Respimat® inhalation solution.
Patients with known hypersensitivity to anticholinergic drugs, lactose, or any other components of the HandiHaler®.
Pregnant or nursing women.
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).
Patients who have previously been randomised in this study or are currently participating in another study.
Patients who are unable to comply with pulmonary medication restrictions prior to randomisation.

Trial locations and contacts

94 sites in 1 country.

City, postcode or hospital

94 sites in 1 country

United States94 sites

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

Other trials in United States

About this study

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]

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: Tiotropium, Placebo matching Olodaterol, Olodaterol
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TiotropiumDrug
marketed product
Placebo matching OlodaterolDrug
one dose
TiotropiumDrug
marketed product
OlodaterolDrug
one dose

Study groups in NCT01696058
Study group	Role	What they receive
Olodaterol andTiotropium	Experimental	2 puffs Olodaterol from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered Receives: Drug: Tiotropium; Drug: Olodaterol
Placebo and Tiotropium	Other	2 puffs placebo inhalation solution from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered Receives: Drug: Tiotropium; Drug: Placebo matching Olodaterol

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (9)

Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data
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.
Measured: 12 weeks
Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline
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.
Measured: baseline and 12 weeks
FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline
Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. AUC was standardized by dividing by time unit.
Measured: baseline and 12 Weeks
Peak FVC Response at 12 Weeks; Defined as Change From Baseline
Peak FVC response at 12 weeks - defined as change from baseline.
Measured: baseline and 12 weeks
Trough FVC Response at 12 Weeks; Defined as Change From Baseline
Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline.
Measured: baseline and 12 weeks
Rescue Medication Usage - Percentage of Rescue Free Days
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)
Measured: over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)
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)
Measured: over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)
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)
Measured: over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)
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)
Measured: over 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2012Oct 2013

First posted28 Sep 2012 (estimated)
Study startSep 2012
Primary completionOct 2013
Study completionOct 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Enrolment: 1,137 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01696058
Sponsor's protocol ID: 1222.52
Status last verified: Nov 2014
First submitted: 26 Sep 2012
Last updated: 25 Nov 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

ZuWallack R, Allen L, Hernandez G, Ting N, Abrahams R. Efficacy and safety of combining olodaterol Respimat((R)) and tiotropium HandiHaler((R)) in patients with COPD: results of two randomized, double-blind, active-controlled studies. Int J Chron Obstruct Pulmon Dis. 2014 Oct 14;9:1133-44. doi: 10.2147/COPD.S72482. eCollection 2014.
PubMed 25342898

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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]
ClinicalTrials.gov ID: NCT01696058
Acronym / sponsor ID: 1222.52
Conditions: Pulmonary Disease, Chronic Obstructive
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,137 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Sep 2012
Primary completion: Oct 2013 (actual)
Study completion: Oct 2013 (actual)
First posted: 28 Sep 2012 (estimated)
Results: Posted 10 Nov 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Number of arms: 2

Arm	Type	Receives
Olodaterol andTiotropium	Experimental	Drug: Tiotropium, Drug: Olodaterol2 puffs Olodaterol from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
Placebo and Tiotropium	Other	Drug: Tiotropium, Drug: Placebo matching Olodaterol2 puffs placebo inhalation solution from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.
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.
Male or female patients, 40 years of age or older.
Patients must be current or ex-smokers with a smoking history of more than 10 pack years
Patients must be able to: perform technically acceptable pulmonary function tests, and maintain records(paper diary).

Key exclusion criteria (27 listed)

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.
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).
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.
A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists).
A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class side effect profile of ß2-agonists).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tiotropiummarketed product	Drug	Placebo and Tiotropium
Placebo matching Olodaterolone dose	Drug	Placebo and Tiotropium
Tiotropiummarketed product	Drug	Olodaterol andTiotropium
Olodaterolone dose	Drug	Olodaterol andTiotropium

Primary outcome

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. 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
Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12

9 secondary outcomes

Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data
Time frame: 12 weeks
Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline
Time frame: baseline and 12 weeks
FVC AUC0-3h 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
Time frame: baseline and 12 weeks
Trough FVC Response at 12 Weeks; Defined as Change From Baseline
Time frame: baseline and 12 weeks
Rescue Medication Usage - Percentage of Rescue Free Days
Time frame: over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)
Time frame: over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)
Time frame: over 12 weeks
Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)
Time frame: over 12 weeks

Results and safety

Results posted to the registry on 10 Nov 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Olodaterol (5μg) and Tiotropium (18μg)	566	523
Placebo and Tiotropium (18μg)	569	538

Primary outcome: FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12

Time frame: baseline and 12 weeks. Least squares mean (Standard Error). Unit: Area Under the Curve (L) (standardized)

Measure	Olodaterol (5μg) and Tiotropium (18μg) n = 563	Placebo and Tiotropium (18μg) n = 566
Value	0.297 (0.010)	0.191 (0.010)

Olodaterol (5μg) and Tiotropium (18μg) vs Placebo and Tiotropium (18μg): Mean Difference (Final Values): 0.106 (95% CI 0.078 to 0.135), p <.0001, Mixed Model Repeated Measure

Population analysed: Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks. FAS included all patients in the treated set who had both baseline and at least one post-baseline measurement at or before 12 weeks for any of the co-primary efficacy variables

Primary outcome: Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12

Time frame: baseline and 12 weeks. Least squares mean (Standard Error). Unit: L

Measure	Olodaterol (5μg) and Tiotropium (18μg) n = 550	Placebo and Tiotropium (18μg) n = 555
Value	0.175 (0.009)	0.135 (0.009)

Olodaterol (5μg) and Tiotropium (18μg) vs Placebo and Tiotropium (18μg): Mean Difference (Final Values): 0.040 (95% CI 0.014 to 0.065), p = 0.0029, Mixed Model Repeated Measure

Population analysed: Full Analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were to be documented throughout the trial, i.e., starting with informed consent and ending 21 days after last administration of trial medication. the duration of treatment was up to 12 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Olodaterol (5μg) and Tiotropium (18μg)	24 of 566 (4.2%)	48 of 566 (8.5%)	Not reported
Placebo and Tiotropium (18μg)	27 of 569 (4.7%)	44 of 569 (7.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25342898ZuWallack R, Allen L, Hernandez G, Ting N, Abrahams R. Efficacy and safety of combining olodaterol Respimat((R)) and tiotropium HandiHaler((R)) in patients with COPD: results of two randomized, double-blind, active-controlled studies. Int J Chron Obstruct Pulmon Dis. 2014 Oct 14;9:1133-44. doi: 10.2147/COPD.S72482. eCollection 2014.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

94 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tiotropium and Olodaterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 94 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 94 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12 (time frame: baseline and 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01696058, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2014.