Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Multiple Dose Comparison of Tiotropium Inhalation Capsules, Salmeterol Inhalation Aerosol and Placebo in a Six-Month, Double-Blind, Double-Dummy, Safety and Efficacy Study in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02173691
• Other study ID #: 205.137
• Status: Completed
• Phase: Phase 3
• First received: June 20, 2014
• Last updated: June 25, 2014
• Start date: February 1999

Study information

• Verified date: June 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustria: Federal Ministry for Health and WomenBelgium: Federal Agency for Medicines and Health Products, FAMHPDenmark: Danish Health and Medicines AuthorityFinland: Ministry of Social Affairs and HealthFrance: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Ministry of HealthIreland: Ministry of HealthItaly: Ministry of HealthNetherlands: Ministry of Health, Welfare and SportNorway: Ministry of Health and Care ServicesSouth Africa: Department of HealthSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to compare the long-term (six month) bronchodilator efficacy and safety of tiotropium inhalation capsules, salmeterol inhalation aerosol and placebo inpatients with COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 584
• Est. primary completion date: May 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Age = 40 years.

• A diagnosis of relatively stable, moderate to severe COPD with:

• Screening FEV1 = 60% of predicted normal value (calculated according to European Community for Coal and Steel (ECCS) criteria and screening FEV1/FVC = 70%

• Smoking history = 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent)

• Ability to be trained in the proper use of the HandiHaler® device and Metered Dose Inhaler (MDI).

• Ability to perform all study related tests including the Shuttle Walking Test, acceptable pulmonary function tests, including Peak expiratory flow rate (PEFR) measurements, and maintenance of diary card records.

• Ability to give written informed consent in accordance with Good Clinical Practice and local regulations.

Exclusion Criteria:

• Clinically significant diseases other than COPD.

• Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion, will be excluded.

• All patients with a serum glutamic oxaloacetic transaminase (SGOT) > 80 IU/L, serum glutamic pyruvic transaminase (SGPT) > 80 IU/L, bilirubin >2.0 mg/dL or creatinine > 2.0 mg/dL will be excluded regardless of clinical condition.

• A recent history (i.e., one year or less) of myocardial infarction.

• Any cardiac arrhythmia requiring drug therapy or hospitalisation for heart failure within the past three years.

• Inability to abstain from regular daytime use of oxygen therapy for more than 1 hour per day.

• Known active tuberculosis.

• History of cancer within the last five years (excluding basal cell carcinoma)

• History of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.

• Patients who have undergone thoracotomy with pulmonary resection.

• Any upper respiratory infection in the past six weeks prior to the screening visit or during the run-in period.

• Current participation in a pulmonary rehabilitation programme or completion of a pulmonary rehabilitation programme in the six week prior to the screening visit.

• Known hypersensitivity to anticholinergic drugs, salmeterol, or any of the components of the lactose powder capsule or MDI delivery systems.

• Known symptomatic prostatic hypertrophy or bladder neck obstruction.

• Patients with known narrow-angle glaucoma.

• Current treatment with cromolyn sodium or nedocromil sodium.

• Current treatment with antihistamines (H1 receptor antagonists).

• 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 prednisolone per day or 20 mg every other day.

• Current use of ß-blocker medication.

• Current treatment with monoamine oxidase inhibitors or tricyclic antidepressants.

• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.

• Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count > 600mm3.

• History of and/or active significant alcohol or drug abuse.

• Concomitant or recent use of an investigational drug within one month or six half lives (whichever is greater) prior to the screening visit.

• Changes in the pulmonary therapeutic plan within the six weeks prior to the screening visit.

• Inability to comply with the medication restrictions specified in Section 4.2 of the trial protocol

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Tiotropium inhalation powder capsules

• Salmeterol inhalation aerosol

• Placebo inhalation aerosol

• Placebo inhalation powder capsules

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough forced expiratory volume in one second (FEV1) response		6 months	No
Primary	Transition Dyspnoea Index (TDI) focal score		6 months	No
Secondary	Average FEV1 response		30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24	No
Secondary	Peak FEV1 response		30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24	No
Secondary	Trough FVC (forced vital capacity) response		30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24	No
Secondary	Average FVC (forced vital capacity) response		30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24	No
Secondary	Peak FVC (forced vital capacity) response		30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24	No
Secondary	Individual FEV1 measurement		Day 1, weeks 2, 8, 16, 24	No
Secondary	Individual FVC measurement		Day 1, weeks 2, 8, 16, 24	No
Secondary	Patient peak expiratory flow rates (PEFR) twice daily		27 weeks	No
Secondary	Physician's global evaluation on an 8-point-scale		27 weeks	No
Secondary	COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chest)		27 weeks	No
Secondary	Amount of salbutamol therapy used during the treatment period		27 weeks	No
Secondary	Number and length of exacerbations of COPD		27 weeks	No
Secondary	Number and length of hospitalizations for respiratory disease		27 weeks	No
Secondary	Changes from baseline in St. George's Hospital Respiratory Questionnaire (SGRQ)		Day 1, week 8, 16, 24 and 27	No
Secondary	Changes from baseline in Mahler Dyspnoea Index (Baseline Dyspnoea Index /Transitional Dyspnoea Index (BDI/TDI))		Baseline, week 8, 16, 24, 27	No
Secondary	Health resource utilisation		27 weeks	No
Secondary	Patient preference measures	patient satisfaction questionnaire score	Day 1 and week 24	No
Secondary	Changes from baseline in Shuttle walking tests (SWT) and Borg dyspnea score		Day 1, week 8, 16, 24, 27	No
Secondary	Occurrence of Adverse Events		27 weeks	No
Secondary	Changes from baseline in pulse rate and blood pressure in conjunction with spirometry		baseline, Day 1, week 2, 8, 16 and 24	No
Secondary	Changes from baseline in physical examination and ECG		baseline and week 24	No
Secondary	Changes from baseline in laboratory tests		baseline and week 24	No

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