Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease II

NCT00796653 | Completed Phase 3 Results

• 2 other identifiers: 1222.142008-001934-28
• Study Type: interventional
• Target: 937
• Locations: 20 countries
• Sites: 98

Brief Summary

The primary objective of this study is to assess the long-term efficacy and safety of once daily treatment of BI 1744 CL inhalation solution (5 and 10 mcg) delivered via the Respimat® inhaler, in patients with COPD.

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (4)

• Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks

  Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

  1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

• Trough FEV1 Response at Week 24

  Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

  1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.

• Mahler Transitional Dyspnea Index Focal Score at 24 Weeks

  Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

  Baseline, Week 24

• Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis

  This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

  Baseline, Week 24

Secondary Outcomes (58)

• Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks

  Baseline, Week 24

• Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks

  Baseline, Week 48

• Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks

  Baseline, Week 12

• Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis

  Baseline, Week 24

• Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks

  1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2

Study Arms (4)

Olodaterol (BI 1744) Low

EXPERIMENTAL

Low dose inhaled orally once daily from the Respimat inhaler

Drug: Olodaterol (BI 1744)

Olodaterol (BI 1744) High

EXPERIMENTAL

High dose inhaled orally once daily from the Respimat inhaler

Drug: Olodaterol (BI 1744)

Formoterol 12mcg

ACTIVE COMPARATOR

12mcg inhaled twice daily from the Aerolizer inhaler

Drug: Formoterol

Placebo

PLACEBO COMPARATOR

Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler

Drug: Placebo

Interventions

Olodaterol (BI 1744) DRUG

Comparison of low and high doses on efficacy and safety in COPD patients

Olodaterol (BI 1744) Low

Formoterol DRUG

Active comparator with Olodaterol (BI 1744) on safety and efficacy in COPD patients

Formoterol 12mcg

Placebo DRUG

Placebo devices for comparison with Olodaterol (BI 1744) on safety and efficacy in COPD patients

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:post-bronchodilator FEV1\<80% of predicted normal (ECSC) 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:

You may not qualify if:

• Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT \>x2 ULN, SGPT \>x2 ULN, bilirubin \>x2 ULN or creatinine \>x2 ULN
• Patients with a history of asthma and/or total blood eosinophil count greater than 600/mm3
• Patients with thyrotoxicosis, paroxysmal tachycardia (\>100 beats per minute)
• Patients with a history of myocardial infarction within 1 year of screening visit, 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, life-threatening pulmonary obstruction, cystic fibrosis, clinically evident bronchiectasis, significant alcohol or drug abuse
• Patients who have undergone thoracotomy with pulmonary resection
• Patients being treated with oral beta-adrenergics or 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.
• 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
• Pregnant or nursing women
• Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (98)

1222.14.5004 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

Location

1222.14.5003 Boehringer Ingelheim Investigational Site

Mar del Plata, Argentina

Location

1222.14.5001 Boehringer Ingelheim Investigational Site

Mendoza, Argentina

Location

1222.14.5002 Boehringer Ingelheim Investigational Site

Quilmes, Argentina

Location

1222.14.5005 Boehringer Ingelheim Investigational Site

San Juan Bautista, Argentina

Location

1222.14.5106 Boehringer Ingelheim Investigational Site

Florianópolis, Brazil

Location

1222.14.5101 Boehringer Ingelheim Investigational Site

Porto Alegre, Brazil

Location

1222.14.5103 Boehringer Ingelheim Investigational Site

Porto Alegre, Brazil

Location

1222.14.5104 Boehringer Ingelheim Investigational Site

Porto Alegre, Brazil

Location

1222.14.5102 Boehringer Ingelheim Investigational Site

Recife, Brazil

Location

1222.14.5105 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

Location

1222.14.4005 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

1222.14.4002 Boehringer Ingelheim Investigational Site

Kelowna, British Columbia, Canada

Location

1222.14.4004 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

1222.14.4009 Boehringer Ingelheim Investigational Site

Moncton, New Brunswick, Canada

Location

1222.14.4010 Boehringer Ingelheim Investigational Site

St. John's, Newfoundland and Labrador, Canada

Location

1222.14.4008 Boehringer Ingelheim Investigational Site

Grimsby, Ontario, Canada

Location

1222.14.4014 Boehringer Ingelheim Investigational Site

Mississauga, Ontario, Canada

Location

1222.14.4007 Boehringer Ingelheim Investigational Site

Newmarket, Ontario, Canada

Location

1222.14.4013 Boehringer Ingelheim Investigational Site

Ottawa, Ontario, Canada

Location

1222.14.4001 Boehringer Ingelheim Investigational Site

Scarborough Village, Ontario, Canada

Location

1222.14.4012 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1222.14.4006 Boehringer Ingelheim Investigational Site

Québec, Quebec, Canada

Location

1222.14.4015 Boehringer Ingelheim Investigational Site

Sherbrooke, Quebec, Canada

Location

1222.14.4011 Boehringer Ingelheim Investigational Site

Saskatoon, Saskatchewan, Canada

Location

1222.14.6004 Boehringer Ingelheim Investigational Site

Brno, Czechia

Location

1222.14.6003 Boehringer Ingelheim Investigational Site

Hradec Králové, Czechia

Location

1222.14.6002 Boehringer Ingelheim Investigational Site

Kyjov, Czechia

Location

1222.14.6001 Boehringer Ingelheim Investigational Site

Znojmo, Czechia

Location

1222.14.4602 Boehringer Ingelheim Investigational Site

Elsinore, Denmark

Location

1222.14.4601 Boehringer Ingelheim Investigational Site

Hillerød, Denmark

Location

1222.14.4603 Boehringer Ingelheim Investigational Site

Roskilde, Denmark

Location

1222.14.4702 Boehringer Ingelheim Investigational Site

Espoo, Finland

Location

1222.14.4701 Boehringer Ingelheim Investigational Site

HUS, Finland

Location

1222.14.4703 Boehringer Ingelheim Investigational Site

Lohja, Finland

Location

1222.14.4106 Boehringer Ingelheim Investigational Site

Aschaffenburg, Germany

Location

1222.14.4112 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1222.14.4103 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

1222.14.4110 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

1222.14.4108 Boehringer Ingelheim Investigational Site

Gelnhausen, Germany

Location

1222.14.4107 Boehringer Ingelheim Investigational Site

Kelkheim, Germany

Location

1222.14.4114 Boehringer Ingelheim Investigational Site

Lübeck, Germany

Location

1222.14.4111 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1222.14.4113 Boehringer Ingelheim Investigational Site

Minden, Germany

Location

1222.14.4109 Boehringer Ingelheim Investigational Site

Mönchengladbach, Germany

Location

1222.14.4104 Boehringer Ingelheim Investigational Site

Rodgau-Dudenhofen, Germany

Location

1222.14.4105 Boehringer Ingelheim Investigational Site

Wiesloch, Germany

Location

1222.14.5501 Boehringer Ingelheim Investigational Site

Hong Kong, Hong Kong

Location

1222.14.5412 Boehringer Ingelheim Investigational Site

Coimbatore, India

Location

1222.14.5406 Boehringer Ingelheim Investigational Site

Hyderabad, India

Location

1222.14.5402 Boehringer Ingelheim Investigational Site

Indore, India

Location

1222.14.5405 Boehringer Ingelheim Investigational Site

Jaipur, India

Location

1222.14.5409 Boehringer Ingelheim Investigational Site

Jaipur, India

Location

1222.14.5403 Boehringer Ingelheim Investigational Site

Mangalore, India

Location

1222.14.5407 Boehringer Ingelheim Investigational Site

Mysore, India

Location

1222.14.5404 Boehringer Ingelheim Investigational Site

Nagpur, India

Location

1222.14.5408 Boehringer Ingelheim Investigational Site

Noida, India

Location

1222.14.5401 Boehringer Ingelheim Investigational Site

Pune, India

Location

1222.14.5410 Boehringer Ingelheim Investigational Site

Vellore, India

Location

1222.14.4301 Boehringer Ingelheim Investigational Site

Cassano Delle Murge (ba), Italy

Location

1222.14.4302 Boehringer Ingelheim Investigational Site

Genova, Italy

Location

1222.14.4304 Boehringer Ingelheim Investigational Site

Milan, Italy

Location

1222.14.4305 Boehringer Ingelheim Investigational Site

Parma, Italy

Location

1222.14.4303 Boehringer Ingelheim Investigational Site

Roma, Italy

Location

1222.14.5701 Boehringer Ingelheim Investigational Site

Georgetown, Pulau Pinang, Malaysia

Location

1222.14.5703 Boehringer Ingelheim Investigational Site

Kuala Lumpur, Malaysia

Location

1222.14.5702 Boehringer Ingelheim Investigational Site

Kuching, Sarawak, Malaysia

Location

1222.14.4802 Boehringer Ingelheim Investigational Site

Fredrikstad, Norway

Location

1222.14.4801 Boehringer Ingelheim Investigational Site

Ski, Norway

Location

1222.14.5802 Boehringer Ingelheim Investigational Site

Iloilo City, Philippines

Location

1222.14.5803 Boehringer Ingelheim Investigational Site

Iloilo City, Philippines

Location

1222.14.5801 Boehringer Ingelheim Investigational Site

Manila, Philippines

Location

1222.14.6103 Boehringer Ingelheim Investigational Site

Brasov, Romania

Location

1222.14.6102 Boehringer Ingelheim Investigational Site

Constanța, Romania

Location

1222.14.6101 Boehringer Ingelheim Investigational Site

Iași, Romania

Location

1222.14.6203 Boehringer Ingelheim Investigational Site

Petrozavodsk, Russia

Location

1222.14.6201 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1222.14.6202 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

1222.14.4901 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1222.14.4902 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

1222.14.5301 Boehringer Ingelheim Investigational Site

Bucheon-si, South Korea

Location

1222.14.5302 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1222.14.5305 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1222.14.5306 Boehringer Ingelheim Investigational Site

Seoul, South Korea

Location

1222.14.5304 Boehringer Ingelheim Investigational Site

Uijeongbu-si, South Korea

Location

1222.14.5303 Boehringer Ingelheim Investigational Site

Wŏnju, South Korea

Location

1222.14.4401 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1222.14.4402 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1222.14.4406 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1222.14.4405 Boehringer Ingelheim Investigational Site

Mérida, Spain

Location

1222.14.4403 Boehringer Ingelheim Investigational Site

Palma de Mallorca, Spain

Location

1222.14.4407 Boehringer Ingelheim Investigational Site

Terrassa (Barcelona), Spain

Location

1222.14.4501 Boehringer Ingelheim Investigational Site

Boden, Sweden

Location

1222.14.4503 Boehringer Ingelheim Investigational Site

Göteboerg, Sweden

Location

1222.14.4502 Boehringer Ingelheim Investigational Site

Lund, Sweden

Location

1222.14.5904 Boehringer Ingelheim Investigational Site

Bangkok, Thailand

Location

1222.14.5901 Boehringer Ingelheim Investigational Site

Khon Kaen, Thailand

Location

1222.14.5902 Boehringer Ingelheim Investigational Site

Songkhla, Thailand

Location

Related Publications (4)

• Singh D, Wedzicha JA, Siddiqui S, de la Hoz A, Xue W, Magnussen H, Miravitlles M, Chalmers JD, Calverley PMA. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020 Sep 17;21(1):240. doi: 10.1186/s12931-020-01482-1.

  PMID: 32943047 DERIVED

• Andreas S, Bothner U, de la Hoz A, Kloer I, Trampisch M, Alter P. A Post Hoc Holter ECG Analysis of Olodaterol and Formoterol in Moderate-to-Very-Severe COPD. Int J Chron Obstruct Pulmon Dis. 2020 Aug 10;15:1955-1965. doi: 10.2147/COPD.S246353. eCollection 2020.

  PMID: 32848381 DERIVED

• Andreas S, Bothner U, Trampisch M, Haensel M, Buhl R, Alter P. Effect of long-acting beta2-agonists olodaterol and formoterol on heart rate and blood pressure in chronic obstructive pulmonary disease patients. Pulm Pharmacol Ther. 2018 Oct;52:1-6. doi: 10.1016/j.pupt.2018.08.002. Epub 2018 Aug 2.

  PMID: 30077810 DERIVED

• Koch A, Pizzichini E, Hamilton A, Hart L, Korducki L, De Salvo MC, Paggiaro P. Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat(R) versus placebo and formoterol twice daily in patients with GOLD 2-4 COPD: results from two replicate 48-week studies. Int J Chron Obstruct Pulmon Dis. 2014 Jul 5;9:697-714. doi: 10.2147/COPD.S62502. eCollection 2014.

  PMID: 25045258 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

olodaterol; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 21, 2008
• First Posted: November 24, 2008
• Study Start: January 1, 2009
• Primary Completion: December 1, 2010
• Last Updated: June 27, 2014
• Results First Posted: June 16, 2014

Record last verified: 2014-06

Locations

FI (3); CA (14); ES (6); NO (2); SE (3); IN (11); CZ (4); MY (3); DE (12); IT (5); RU (3); PH (3); BR (6); ZA (2); KR (6); AR (5); RO (3); HK (1); DK (3); TH (3)