Clinical trial NCT01694771: Co-administration of Olodaterol Respimat® and Tiotropium Handihaler®
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 1]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-09-27
Enrollment: 1134
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12
timeFrame: baseline and 12 weeks
measure: Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12
timeFrame: baseline and 12 weeks
Secondary outcomes:
measure: Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline
timeFrame: baseline and 12 weeks
measure: FVC AUC0-3h Response at 12 Weeks - Defined as Change From Baseline
timeFrame: baseline and 12 weeks
measure: Trough FVC Response at 12 Weeks- Defined as Change From Baseline
timeFrame: baseline and 12 weeks
measure: Peak FVC Response at 12 Weeks - Defined as Change From Baseline
timeFrame: baseline and 12 weeks
measure: Rescue Medication Usage - Percentage of Rescue Free Days
timeFrame: over 12 weeks
measure: Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)
timeFrame: over 12 weeks
measure: Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)
timeFrame: over 12 weeks
measure: Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)
timeFrame: over 12 weeks
Other outcomes:
Locations:
city: Florence
country: United States
facility: 1222.51.01055 Boehringer Ingelheim Investigational Site
state: Alabama
city: Jasper
country: United States
facility: 1222.51.01087 Boehringer Ingelheim Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: 1222.51.01066 Boehringer Ingelheim Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: 1222.51.01069 Boehringer Ingelheim Investigational Site
state: Arizona
city: Anaheim
country: United States
facility: 1222.51.01040 Boehringer Ingelheim Investigational Site
state: California
city: Encinitas
country: United States
facility: 1222.51.01064 Boehringer Ingelheim Investigational Site
state: California
city: Fullerton
country: United States
facility: 1222.51.01060 Boehringer Ingelheim Investigational Site
state: California
city: Lincoln
country: United States
facility: 1222.51.01084 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1222.51.01041 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1222.51.01094 Boehringer Ingelheim Investigational Site
state: California
city: Torrance
country: United States
facility: 1222.51.01015 Boehringer Ingelheim Investigational Site
state: California
city: Boulder
country: United States
facility: 1222.51.01052 Boehringer Ingelheim Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: 1222.51.01010 Boehringer Ingelheim Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: 1222.51.01042 Boehringer Ingelheim Investigational Site
state: Colorado
city: Stamford
country: United States
facility: 1222.51.01070 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Clearwater
country: United States
facility: 1222.51.01006 Boehringer Ingelheim Investigational Site
state: Florida
city: Clearwater
country: United States
facility: 1222.51.01021 Boehringer Ingelheim Investigational Site
state: Florida
city: Clearwater
country: United States
facility: 1222.51.01082 Boehringer Ingelheim Investigational Site
state: Florida
city: DeLand
country: United States
facility: 1222.51.01065 Boehringer Ingelheim Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: 1222.51.01051 Boehringer Ingelheim Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: 1222.51.01092 Boehringer Ingelheim Investigational Site
state: Florida
city: Ormond Beach
country: United States
facility: 1222.51.01081 Boehringer Ingelheim Investigational Site
state: Florida
city: Panama City
country: United States
facility: 1222.51.01054 Boehringer Ingelheim Investigational Site
state: Florida
city: Pensacola
country: United States
facility: 1222.51.01062 Boehringer Ingelheim Investigational Site
state: Florida
city: Port Orange
country: United States
facility: 1222.51.01088 Boehringer Ingelheim Investigational Site
state: Florida
city: Tamarac
country: United States
facility: 1222.51.01079 Boehringer Ingelheim Investigational Site
state: Florida
city: Atlanta
country: United States
facility: 1222.51.01075 Boehringer Ingelheim Investigational Site
state: Georgia
city: Austell
country: United States
facility: 1222.51.01076 Boehringer Ingelheim Investigational Site
state: Georgia
city: Duluth
country: United States
facility: 1222.51.01057 Boehringer Ingelheim Investigational Site
state: Georgia
city: Lawrenceville
country: United States
facility: 1222.51.01086 Boehringer Ingelheim Investigational Site
state: Georgia
city: Coeur d'Alene
country: United States
facility: 1222.51.01019 Boehringer Ingelheim Investigational Site
state: Idaho
city: Eagle
country: United States
facility: 1222.51.01027 Boehringer Ingelheim Investigational Site
state: Idaho
city: Arlingron Heights
country: United States
facility: 1222.51.01048 Boehringer Ingelheim Investigational Site
state: Illinois
city: River Forest
country: United States
facility: 1222.51.01044 Boehringer Ingelheim Investigational Site
state: Illinois
city: Skokie
country: United States
facility: 1222.51.01043 Boehringer Ingelheim Investigational Site
state: Illinois
city: Louisville
country: United States
facility: 1222.51.01090 Boehringer Ingelheim Investigational Site
state: Kentucky
city: Lafayette
country: United States
facility: 1222.51.01023 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Opelousas
country: United States
facility: 1222.51.01071 Boehringer Ingelheim Investigational Site
state: Louisiana
city: North Dartmouth
country: United States
facility: 1222.51.01050 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: 1222.51.01049 Boehringer Ingelheim Investigational Site
state: Michigan
city: Livonia
country: United States
facility: 1222.51.01025 Boehringer Ingelheim Investigational Site
state: Michigan
city: Edina
country: United States
facility: 1222.51.01078 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Fridley
country: United States
facility: 1222.51.01033 Boehringer Ingelheim Investigational Site
state: Minnesota
city: St. Charles
country: United States
facility: 1222.51.01074 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 1222.51.01037 Boehringer Ingelheim Investigational Site
state: Missouri
city: Reno
country: United States
facility: 1222.51.01039 Boehringer Ingelheim Investigational Site
state: Nevada
city: Larchmont
country: United States
facility: 1222.51.01045 Boehringer Ingelheim Investigational Site
state: New York
city: Rochester
country: United States
facility: 1222.51.01018 Boehringer Ingelheim Investigational Site
state: New York
city: Asheville
country: United States
facility: 1222.51.01014 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: 1222.51.01077 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: 1222.51.01056 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Canton
country: United States
facility: 1222.51.01032 Boehringer Ingelheim Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: 1222.51.01011 Boehringer Ingelheim Investigational Site
state: Ohio
city: Columbus
country: United States
facility: 1222.51.01005 Boehringer Ingelheim Investigational Site
state: Ohio
city: Dayton
country: United States
facility: 1222.51.01093 Boehringer Ingelheim Investigational Site
state: Ohio
city: Sylvania
country: United States
facility: 1222.51.01089 Boehringer Ingelheim Investigational Site
state: Ohio
city: Toledo
country: United States
facility: 1222.51.01080 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 1222.51.01017 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Tulsa
country: United States
facility: 1222.51.01047 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Corvallis
country: United States
facility: 1222.51.01031 Boehringer Ingelheim Investigational Site
state: Oregon
city: Medford
country: United States
facility: 1222.51.01020 Boehringer Ingelheim Investigational Site
state: Oregon
city: Portland
country: United States
facility: 1222.51.01053 Boehringer Ingelheim Investigational Site
state: Oregon
city: Erie
country: United States
facility: 1222.51.01016 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: 1222.51.01004 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: East Providence
country: United States
facility: 1222.51.01030 Boehringer Ingelheim Investigational Site
state: Rhode Island
city: Johnston
country: United States
facility: 1222.51.01009 Boehringer Ingelheim Investigational Site
state: Rhode Island
city: Charleston
country: United States
facility: 1222.51.01036 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Columbia
country: United States
facility: 1222.51.01061 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Easley
country: United States
facility: 1222.51.01038 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Easley
country: United States
facility: 1222.51.01046 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Gaffney
country: United States
facility: 1222.51.01022 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1222.51.01063 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greer
country: United States
facility: 1222.51.01013 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1222.51.01024 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Union
country: United States
facility: 1222.51.01012 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Rapid City
country: United States
facility: 1222.51.01008 Boehringer Ingelheim Investigational Site
state: South Dakota
city: Johnson City
country: United States
facility: 1222.51.01035 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Boerne
country: United States
facility: 1222.51.01028 Boehringer Ingelheim Investigational Site
state: Texas
city: Corsicana
country: United States
facility: 1222.51.01083 Boehringer Ingelheim Investigational Site
state: Texas
city: Killeen
country: United States
facility: 1222.51.01085 Boehringer Ingelheim Investigational Site
state: Texas
city: Longview
country: United States
facility: 1222.51.01073 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1222.51.01003 Boehringer Ingelheim Investigational Site
state: Texas
city: Murray
country: United States
facility: 1222.51.01058 Boehringer Ingelheim Investigational Site
state: Utah
city: Abingdon
country: United States
facility: 1222.51.01068 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1222.51.01029 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1222.51.01034 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1222.51.01072 Boehringer Ingelheim Investigational Site
state: Virginia
city: Spokane
country: United States
facility: 1222.51.01091 Boehringer Ingelheim Investigational Site
state: Washington
city: Vancouver
country: United States
facility: 1222.51.01002 Boehringer Ingelheim Investigational Site
state: Washington
city: Morgantown
country: United States
facility: 1222.51.01001 Boehringer Ingelheim Investigational Site
state: West Virginia
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.