Clinical trial NCT03240575: The ENERGITO® 2 Study Compares 2 Inhaled Medicines for Chronic Obstructive Pulmonary Disease (COPD). One Medicine is a Combination of Tiotropium and Olodaterol (Stiolto®) Taken Using the Respimat® Inhaler and the Other Medicine is a Combination of Fluticasone and Salmeterol Taken Using the Diskus
Official title: A Randomized, Double-blind, Double-dummy, Active-controlled, Multi-center, Parallel Group Study to Show the Superiority in Lung Function of 12 Weeks Once Daily Treatment With Orally Inhaled Tiotropium+Olodaterol Fixed Dose Combination Delivered by the Respimat® Inhaler vs. 12 Weeks Twice Daily Treatment With Fluticasone Propionate+Salmeterol Fixed Dose Combination Delivered by the Diskus® in Patients With Chronic Obstructive Pulmonary Disease (COPD) [ENERGITO® 2]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2017-08-07
Enrollment: 302
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 primary objective of the trial is to show superiority in lung function of once daily (2 inhalations) treatment with orally inhaled tiotropium+olodaterol fixed dose combination to twice daily (one inhalation) treatment with fluticasone propionate+salmeterol fixed dose combination over 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD).

A Digital Health (DH) exploratory study has been integrated into the main study as a site specific study. The DH exploratory study will be performed at a single site; the site is also participating in the main study. The DH exploratory study site will enter (randomize) approximately 20 patients (subjects) (in addition to the patients to be enrolled in the main study at this site). The patients enrolled in the DH exploratory study are not considered to be part of the main study (i.e. data collected in the DH exploratory study will be analyzed separately from the data collected in the main study).


Eligibility criteria: Inclusion Criteria:

* All patients must sign an informed consent consistent with FDA regulations 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 with a post-bronchodilator 30% ≤ Forced Expiratory Volume in one second (FEV1) \<80% of predicted normal (European Coal and Steel Community( ECSC)); and a post-bronchodilator FEV1/Forced Vital Capacity (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 who have never smoked cigarettes must be excluded.
* Patients must be able to perform, according to investigator's judgment, all trial related procedures including:

  * Technically acceptable pulmonary function tests (spirometry)
  * Completion of study questionnaires
* Patients must be able to inhale medication in a competent manner (in the opinion of the investigator) from the Respimat® and Diskus® inhalers and from a metered dose inhaler (MDI).

Exclusion Criteria:

* Patients with a significant disease other than Chronic Obstructive Pulmonary Disease (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 patient's ability to participate in the study.
* Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the last 3 months prior to Visit 1 and/or between Visit 1 and Visit 2.
* 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 nonasthmatic condition.

Patients with any of the following conditions:

* 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).
* 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 the first exclusion criterion).
* Patients being treated with oral or patch β-adrenergics.
* Patients being treated with oral corticosteroid medication within 6 weeks prior to Visit 1.
* Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's 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, six half-lives or within the wash out period (whichever is greater) prior to screening visit (Visit 1).
* Patients with known hypersensitivity to β-adrenergic drugs, BAC, EDTA, or any other component of the Respimat® inhalation solution. In addition, patients with known hypersensitivity to Lactose monohydrate (which contains milk proteins).
* Pregnant or nursing women.
* Women of childbearing potential not using a method of birth control classified at least as "acceptable". Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or post-menopausal (defined as no menses for 12 months without an alternative medical cause). Tubal ligation is NOT a method of permanent sterilisation.
* Patients who have previously been randomized in this study or are currently participating in another study.
* Patients who are unable to comply with pulmonary medication restrictions prior to randomization.

Primary outcomes:
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 24 Hours (AUC0-24) Response (Change From Baseline) [L] After 12 Weeks of Treatment
timeFrame: 1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline.10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min, 12h 30 min, 13h, 14h, 22h, 23h, and 24h post morning dose at week 12.
Secondary outcomes:
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 12 Hours (AUC0-12) Response (Change From Baseline) [L] After 12 Weeks of Treatment
timeFrame: 1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline. 10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min post morning dose at week 12.
measure: Trough Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment
timeFrame: At 23 h and 24 h post dose at baseline and at 23h and 24 h post dose at week 12.
measure: Peak 0-3 Hours Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment
timeFrame: 30 minutes, 1 h, 2h and 3h post dose at baseline and week 12.
Other outcomes:
Locations:
city: Jasper
country: United States
facility: Jasper Summit Research, LLC
state: Alabama
city: Flagstaff
country: United States
facility: Clinical Trial Connection
state: Arizona
city: Fullerton
country: United States
facility: California Research Medical Group, Inc.
state: California
city: Huntington Beach
country: United States
facility: Allergy and Asthma Specialists Medical Group
state: California
city: Northridge
country: United States
facility: California Medical Research Associates Inc.
state: California
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC, Inc
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Duluth
country: United States
facility: Duluth Biomedical Research
state: Georgia
city: Marietta
country: United States
facility: DC Pulmonary Medicine
state: Georgia
city: New Orleans
country: United States
facility: New Orleans Center for Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Farmington Hills
country: United States
facility: Pulmonary Rsrch Inst of SE MI
state: Michigan
city: Edina
country: United States
facility: Minnesota Lung Center and Sleep Institute
state: Minnesota
city: Minneapolis
country: United States
facility: Clinical Research Institute Inc
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Lung Center
state: Minnesota
city: Saint Louis
country: United States
facility: The Clinical Research Center, LLC
state: Missouri
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: Gastonia
country: United States
facility: Gastonia Pharmaceutical Research, LLC
state: North Carolina
city: Hendersonville
country: United States
facility: Hendersonville Pharmaceutical Research
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: Bernstein Clinical Rsrch Ctr
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Dublin
country: United States
facility: Aventiv Research Inc.
state: Ohio
city: Edmond
country: United States
facility: OK Clinical Research, LLC
state: Oklahoma
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Philadelphia
country: United States
facility: Arcuri Clinical Research, LLC
state: Pennsylvania
city: Charleston
country: United States
facility: Lowcountry Lung and Critical Care
state: South Carolina
city: Easley
country: United States
facility: VitaLink Research - Easley
state: South Carolina
city: Gaffney
country: United States
facility: VitaLink Research -Gaffney
state: South Carolina
city: Greenville
country: United States
facility: VitaLink Research
state: South Carolina
city: Rock Hill
country: United States
facility: Vita Link Research- Rock Hill
state: South Carolina
city: Spartanburg
country: United States
facility: South Carolina Pharma Rsrch
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Plano
country: United States
facility: Advanced Clinical Research Associates
state: Texas
city: Sherman
country: United States
facility: Sherman Clinical Research
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond, Inc.
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Morgantown
country: United States
facility: Morgantown Pulmonary ClinRsrch
state: West Virginia
Study officials:
References: