Clinical trial NCT01696058: 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 2]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-09-28
Enrollment: 1137
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: Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data
timeFrame: 12 weeks
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: Peak FVC 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: 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: Anniston
country: United States
facility: 1222.52.02090 Boehringer Ingelheim Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: 1222.52.02046 Boehringer Ingelheim Investigational Site
state: Alabama
city: Mobile
country: United States
facility: 1222.52.02014 Boehringer Ingelheim Investigational Site
state: Alabama
city: Montgomery
country: United States
facility: 1222.52.02017 Boehringer Ingelheim Investigational Site
state: Alabama
city: Anchorage
country: United States
facility: 1222.52.02092 Boehringer Ingelheim Investigational Site
state: Alaska
city: Chandler
country: United States
facility: 1222.52.02072 Boehringer Ingelheim Investigational Site
state: Arizona
city: Glendale
country: United States
facility: 1222.52.02063 Boehringer Ingelheim Investigational Site
state: Arizona
city: Peoria
country: United States
facility: 1222.52.02088 Boehringer Ingelheim Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: 1222.52.02012 Boehringer Ingelheim Investigational Site
state: Arizona
city: Huntington Beach
country: United States
facility: 1222.52.02006 Boehringer Ingelheim Investigational Site
state: California
city: San Jose
country: United States
facility: 1222.52.02031 Boehringer Ingelheim Investigational Site
state: California
city: Torrance
country: United States
facility: 1222.52.02011 Boehringer Ingelheim Investigational Site
state: California
city: Boulder
country: United States
facility: 1222.52.02061 Boehringer Ingelheim Investigational Site
state: Colorado
city: Fort Collins
country: United States
facility: 1222.52.02054 Boehringer Ingelheim Investigational Site
state: Colorado
city: Hartford
country: United States
facility: 1222.52.02001 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Norwalk
country: United States
facility: 1222.52.02037 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Waterbury
country: United States
facility: 1222.52.02055 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Clearwater
country: United States
facility: 1222.52.02094 Boehringer Ingelheim Investigational Site
state: Florida
city: Fort Lauderdale
country: United States
facility: 1222.52.02022 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 1222.52.02074 Boehringer Ingelheim Investigational Site
state: Florida
city: Ponte Verda
country: United States
facility: 1222.52.02016 Boehringer Ingelheim Investigational Site
state: Florida
city: St. Petersberg
country: United States
facility: 1222.52.02084 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1222.52.02043 Boehringer Ingelheim Investigational Site
state: Florida
city: Blue Ridge
country: United States
facility: 1222.52.02009 Boehringer Ingelheim Investigational Site
state: Georgia
city: Duluth
country: United States
facility: 1222.52.02048 Boehringer Ingelheim Investigational Site
state: Georgia
city: Gainsville
country: United States
facility: 1222.52.02077 Boehringer Ingelheim Investigational Site
state: Georgia
city: Rincon
country: United States
facility: 1222.52.02040 Boehringer Ingelheim Investigational Site
state: Georgia
city: O'Fallon
country: United States
facility: 1222.52.02024 Boehringer Ingelheim Investigational Site
state: Illinois
city: Muncie
country: United States
facility: 1222.52.02002 Boehringer Ingelheim Investigational Site
state: Indiana
city: Fort Mitchell
country: United States
facility: 1222.52.02008 Boehringer Ingelheim Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: 1222.52.02025 Boehringer Ingelheim Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: 1222.52.02089 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: 1222.52.02005 Boehringer Ingelheim Investigational Site
state: Maryland
city: Columbia
country: United States
facility: 1222.52.02029 Boehringer Ingelheim Investigational Site
state: Maryland
city: Hollywood
country: United States
facility: 1222.52.02036 Boehringer Ingelheim Investigational Site
state: Maryland
city: Townson
country: United States
facility: 1222.52.02015 Boehringer Ingelheim Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: 1222.52.02034 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Chelsea
country: United States
facility: 1222.52.02003 Boehringer Ingelheim Investigational Site
state: Michigan
city: Kalamazoo
country: United States
facility: 1222.52.02020 Boehringer Ingelheim Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: 1222.52.02047 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Minneapolis
country: United States
facility: 1222.52.02049 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Plymouth
country: United States
facility: 1222.52.02079 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Chesterfield
country: United States
facility: 1222.52.02068 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 1222.52.02028 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 1222.52.02053 Boehringer Ingelheim Investigational Site
state: Missouri
city: Billings
country: United States
facility: 1222.52.02050 Boehringer Ingelheim Investigational Site
state: Montana
city: Henderson
country: United States
facility: 1222.52.02035 Boehringer Ingelheim Investigational Site
state: Nevada
city: Marlton
country: United States
facility: 1222.52.02030 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: 1222.52.02071 Boehringer Ingelheim Investigational Site
state: New Mexico
city: Johnson City
country: United States
facility: 1222.52.02064 Boehringer Ingelheim Investigational Site
state: New York
city: New Windsor
country: United States
facility: 1222.52.02087 Boehringer Ingelheim Investigational Site
state: New York
city: Syracuse
country: United States
facility: 1222.52.02091 Boehringer Ingelheim Investigational Site
state: New York
city: Calabash
country: United States
facility: 1222.52.02076 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Huntersville
country: United States
facility: 1222.52.02010 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: 1222.52.02045 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Salisbury
country: United States
facility: 1222.52.02038 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Shelby
country: United States
facility: 1222.52.02051 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Tabor City
country: United States
facility: 1222.52.02058 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Winston Salem
country: United States
facility: 1222.52.02013 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: 1222.52.02062 Boehringer Ingelheim Investigational Site
state: Ohio
city: Columbus
country: United States
facility: 1222.52.02039 Boehringer Ingelheim Investigational Site
state: Ohio
city: Columbus
country: United States
facility: 1222.52.02081 Boehringer Ingelheim Investigational Site
state: Ohio
city: Columbus
country: United States
facility: 1222.52.02093 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 1222.52.02059 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: 1222.52.02026 Boehringer Ingelheim Investigational Site
state: Oregon
city: Medford
country: United States
facility: 1222.52.02097 Boehringer Ingelheim Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: 1222.52.02075 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: 1222.52.02102 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: 1222.52.02080 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1222.52.02100 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Easley
country: United States
facility: 1222.52.02096 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1222.52.02085 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1222.52.02101 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Hodges
country: United States
facility: 1222.52.02065 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Myrtle Beach
country: United States
facility: 1222.52.02042 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Rock Hill
country: United States
facility: 1222.52.02083 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1222.52.02066 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1222.52.02095 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Union
country: United States
facility: 1222.52.02098 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Brentwood
country: United States
facility: 1222.52.02018 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Arlington
country: United States
facility: 1222.52.02086 Boehringer Ingelheim Investigational Site
state: Texas
city: Austin
country: United States
facility: 1222.52.02044 Boehringer Ingelheim Investigational Site
state: Texas
city: El Paso
country: United States
facility: 1222.52.02041 Boehringer Ingelheim Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: 1222.52.02027 Boehringer Ingelheim Investigational Site
state: Texas
city: Houston
country: United States
facility: 1222.52.02056 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1222.52.02007 Boehringer Ingelheim Investigational Site
state: Texas
city: San Antonio
country: United States
facility: 1222.52.02060 Boehringer Ingelheim Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: 1222.52.02078 Boehringer Ingelheim Investigational Site
state: Texas
city: Waco
country: United States
facility: 1222.52.02082 Boehringer Ingelheim Investigational Site
state: Texas
city: Midvale
country: United States
facility: 1222.52.02057 Boehringer Ingelheim Investigational Site
state: Utah
city: Richmond
country: United States
facility: 1222.52.02023 Boehringer Ingelheim Investigational Site
state: Virginia
city: Selah
country: United States
facility: 1222.52.02069 Boehringer Ingelheim Investigational Site
state: Washington
city: Tacoma
country: United States
facility: 1222.52.02019 Boehringer Ingelheim Investigational Site
state: Washington
city: Morgantown
country: United States
facility: 1222.52.02099 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.