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

NCT00793624 | Completed Phase 3 Results

• 2 other identifiers: 1222.132008-001933-84
• Study Type: interventional
• Target: 906
• Locations: 20 countries
• Sites: 93

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 12 Weeks

  Baseline, Week 12

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

  Baseline, Week 48

• 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 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 (93)

1222.13.2401 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

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1222.13.2403 Boehringer Ingelheim Investigational Site

Capital Federal, Argentina

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1222.13.2402 Boehringer Ingelheim Investigational Site

Mar del Plata, Argentina

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1222.13.2404 Boehringer Ingelheim Investigational Site

Monte Grande, Argentina

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1222.13.2502 Boehringer Ingelheim Investigational Site

Juiz de Fora, Brazil

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1222.13.2503 Boehringer Ingelheim Investigational Site

Rio de Janeiro, Brazil

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1222.13.2505 Boehringer Ingelheim Investigational Site

Rio de Janeiro, Brazil

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1222.13.2501 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

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1222.13.2504 Boehringer Ingelheim Investigational Site

São Paulo, Brazil

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1222.13.1408 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

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1222.13.1407 Boehringer Ingelheim Investigational Site

Chilliwack, British Columbia, Canada

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1222.13.1403 Boehringer Ingelheim Investigational Site

Downsview, Ontario, Canada

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1222.13.1412 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

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1222.13.1401 Boehringer Ingelheim Investigational Site

Niagara Falls, Ontario, Canada

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1222.13.1410 Boehringer Ingelheim Investigational Site

Sarnia, Ontario, Canada

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1222.13.1413 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

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1222.13.1404 Boehringer Ingelheim Investigational Site

La Malbaie, Quebec, Canada

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1222.13.1411 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

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1222.13.1406 Boehringer Ingelheim Investigational Site

Point Claire, Quebec, Canada

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1222.13.1402 Boehringer Ingelheim Investigational Site

Saskatoon, Saskatchewan, Canada

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1222.13.3502 Boehringer Ingelheim Investigational Site

Dubrovnik, Croatia

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1222.13.3503 Boehringer Ingelheim Investigational Site

Rijeka, Croatia

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1222.13.3504 Boehringer Ingelheim Investigational Site

Split, Croatia

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1222.13.3501 Boehringer Ingelheim Investigational Site

Zagreb, Croatia

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1222.13.3401 Boehringer Ingelheim Investigational Site

Beroun, Czechia

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1222.13.3403 Boehringer Ingelheim Investigational Site

Český Těšín, Czechia

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1222.13.3402 Boehringer Ingelheim Investigational Site

Tábor, Czechia

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1222.13.2003 Boehringer Ingelheim Investigational Site

Aalborg, Denmark

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1222.13.2002 Boehringer Ingelheim Investigational Site

Hvidovre, Denmark

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1222.13.2001 Boehringer Ingelheim Investigational Site

Silkeborg, Denmark

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1222.13.2103 Boehringer Ingelheim Investigational Site

Lahti, Finland

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1222.13.2101 Boehringer Ingelheim Investigational Site

Tampere, Finland

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1222.13.2102 Boehringer Ingelheim Investigational Site

Turku, Finland

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1222.13.1502 Boehringer Ingelheim Investigational Site

Berlin, Germany

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1222.13.1503 Boehringer Ingelheim Investigational Site

Berlin, Germany

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1222.13.1506 Boehringer Ingelheim Investigational Site

Berlin, Germany

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1222.13.1501 Boehringer Ingelheim Investigational Site

Cologne, Germany

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Dortmund, Germany

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1222.13.1514 Boehringer Ingelheim Investigational Site

Essen, Germany

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1222.13.1509 Boehringer Ingelheim Investigational Site

Großhansdorf, Germany

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1222.13.1508 Boehringer Ingelheim Investigational Site

Hanover, Germany

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1222.13.1510 Boehringer Ingelheim Investigational Site

Hanover, Germany

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1222.13.1512 Boehringer Ingelheim Investigational Site

Kiel, Germany

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1222.13.1505 Boehringer Ingelheim Investigational Site

Reinfeld, Germany

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1222.13.1507 Boehringer Ingelheim Investigational Site

Schwerin, Germany

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1222.13.2901 Boehringer Ingelheim Investigational Site

Kowloon, Hong Kong

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1222.13.2804 Boehringer Ingelheim Investigational Site

Bangalore, India

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1222.13.2803 Boehringer Ingelheim Investigational Site

Chennai, India

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1222.13.2806 Boehringer Ingelheim Investigational Site

Coimbatore, India

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1222.13.2810 Boehringer Ingelheim Investigational Site

Hyderabad, India

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1222.13.2801 Boehringer Ingelheim Investigational Site

Indore, India

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1222.13.2807 Boehringer Ingelheim Investigational Site

Indore, India

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1222.13.2805 Boehringer Ingelheim Investigational Site

Jaipur, India

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1222.13.2802 Boehringer Ingelheim Investigational Site

Ludhiana, Punjab, India

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1222.13.2809 Boehringer Ingelheim Investigational Site

Mumbai, India

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1222.13.2812 Boehringer Ingelheim Investigational Site

Mumbai, India

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1222.13.2811 Boehringer Ingelheim Investigational Site

Pune, India

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1222.13.1704 Boehringer Ingelheim Investigational Site

Catania, Italy

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1222.13.1702 Boehringer Ingelheim Investigational Site

Genova, Italy

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1222.13.1701 Boehringer Ingelheim Investigational Site

Pisa, Italy

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1222.13.1705 Boehringer Ingelheim Investigational Site

Siena, Italy

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1222.13.1703 Boehringer Ingelheim Investigational Site

Trieste, Italy

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1222.13.3103 Boehringer Ingelheim Investigational Site

Batu Caves, Malaysia

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1222.13.3101 Boehringer Ingelheim Investigational Site

Kota Kinabalu, Malaysia

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1222.13.3102 Boehringer Ingelheim Investigational Site

Kuala Lumpur, Malaysia

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1222.13.3104 Boehringer Ingelheim Investigational Site

Kuantan, Malaysia

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1222.13.2201 Boehringer Ingelheim Investigational Site

Bergen, Norway

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1222.13.2202 Boehringer Ingelheim Investigational Site

Oslo, Norway

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1222.13.3203 Boehringer Ingelheim Investigational Site

Cebu, Philippines

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1222.13.3201 Boehringer Ingelheim Investigational Site

Quezon City, Philippines

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1222.13.3202 Boehringer Ingelheim Investigational Site

Quezon City, Philippines

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1222.13.2302 Boehringer Ingelheim Investigational Site

Durban, South Africa

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1222.13.2301 Boehringer Ingelheim Investigational Site

Pretoria, South Africa

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1222.13.2701 Boehringer Ingelheim Investigational Site

Gwangju, South Korea

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1222.13.2702 Boehringer Ingelheim Investigational Site

Incheon, South Korea

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1222.13.2703 Boehringer Ingelheim Investigational Site

Seoul, South Korea

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1222.13.2705 Boehringer Ingelheim Investigational Site

Seoul, South Korea

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1222.13.2706 Boehringer Ingelheim Investigational Site

Seoul, South Korea

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1222.13.2704 Boehringer Ingelheim Investigational Site

Suwon, South Korea

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1222.13.1803 Boehringer Ingelheim Investigational Site

Aranjuez, Spain

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1222.13.1806 Boehringer Ingelheim Investigational Site

Elda, Spain

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1222.13.1802 Boehringer Ingelheim Investigational Site

els Hostalets de Balenyà, Spain

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1222.13.1804 Boehringer Ingelheim Investigational Site

Pozuelo de Alarcón, Spain

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1222.13.1805 Boehringer Ingelheim Investigational Site

Valladolid, Spain

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1222.13.1801 Boehringer Ingelheim Investigational Site

Vic (Barcelona), Spain

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1222.13.1901 Boehringer Ingelheim Investigational Site

Boden, Sweden

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1222.13.1902 Boehringer Ingelheim Investigational Site

Sundsvall, Sweden

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1222.13.3302 Boehringer Ingelheim Investigational Site

Bangkok, Thailand

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1222.13.3303 Boehringer Ingelheim Investigational Site

Bangkok, Thailand

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1222.13.3301 Boehringer Ingelheim Investigational Site

Chiang Mai, Thailand

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1222.13.3602 Boehringer Ingelheim Investigational Site

Ivano-Frankivsk, Ukraine

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1222.13.3601 Boehringer Ingelheim Investigational Site

Kharkiv, Ukraine

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1222.13.3603 Boehringer Ingelheim Investigational Site

Kiev, Ukraine

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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 18, 2008
• First Posted: November 19, 2008
• Study Start: February 1, 2009
• Primary Completion: December 1, 2010
• Last Updated: June 27, 2014
• Results First Posted: June 5, 2014

Record last verified: 2014-06

Locations

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