Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Pharmacodynamic and Pharmacokinetic Dose Ranging Study of Tiotropium Bromide Administered Via Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD): a Randomized, 3-week Multiple-dose, Placebo Controlled, Intraformulation Double-blind, Parallel Group Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02175342
• Other study ID #: 205.127
• Status: Completed
• Phase: Phase 2
• First received: June 24, 2014
• Last updated: June 25, 2014
• Start date: March 1998

Study information

• Verified date: June 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

This pharmacodynamic and pharmacokinetic dose-ranging study aims to determine the optimal dose of tiotropium inhaled as a solution from a Respimat device once a day for three weeks in patients with COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. primary completion date: April 1999
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Age: = 40 years;

2. Diagnosis of COPD and met the following criteria:

1. Relatively stable, moderate to severe airway obstruction,

2. Baseline 30% = FEV1 = 65% of predicted normal value, predicted normal values are based on the guidelines for standardized lung function testing of the European Community for Coal and Steel (ECCS) ,

3. Baseline FEV1/ forced expiratory vital capacity (FEVC) = 70%;

3. Smoking history = 10 pack-years (p.y.). A p.y. is defined as the equivalent of smoking one pack of cigarettes per day for one year;

4. Male of female;

5. Ability to be trained in the proper use of Respimat and Handihaler;

6. Ability to be trained in the performance of technically satisfactory pulmonary function tests;

7. Ability to provide written informed consent

8. Patient affiliated to the Social Security System

Exclusion Criteria:

1. History of asthma, allergic rhinitis or atopy or who have a blood eosinophil count above 600/mm³

2. Changes in the therapeutic (pulmonary) plan within the last six weeks prior to the Screening Visit;

3. Treatment by cromolyn/nedocromil sodium;

4. Treatment by antihistamines (H1 receptor antagonists);

5. A lower respiratory tract infection or any exacerbation in the past six weeks prior to the Screening Visit;

6. Regular use of daytime oxygen therapy;

7. Treatment by oral corticosteroid medication if initiated or modified within the last six weeks or if daily dose > 10 mg prednisone equivalent;

8. History of life threatening pulmonary obstruction, cystic fibrosis or bronchiectasis

9. Patients who have undergone thoracotomy with pulmonary resection;

10. History of clinically significant cardiovascular, renal neurologic, liver or endocrine dysfunction. A clinically significant disease was defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.

11. Patients with a recent (= one year) history of myocardial infarction, of heart failure or patients with any cardiac arrhythmia requiring drug therapy;

12. Tuberculosis with indication for treatment;

13. History of cancer within the last five years. Patients with treated basal cell carcinoma were allowed:

14. Current psychiatric disorders;

15. Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction;

16. Patients with any history of glaucoma or increased intra-ocular pressure;

17. Patients with clinically significant abnormal baseline haematology or blood chemistry, if the abnormality defines a disease listed as an exclusion criterion;

18. Patients with

1. glutamyl-oxalo-acetic transaminase/glutamyl-pyruvic transaminase (SGOT/SGPT): > 200% of the upper limit of the normal range (ULN, )

2. bilirubin: > 150% of the ULN,

3. creatinine: > 125% of the ULN;

19. Intolerance to aerosolised anticholinergic containing products, and/or hypersensitivity to benzalkonium chloride, to lactose or any other components of the inhalation capsule delivery system;

20. Beta-blocker medication;

21. Concomitant or recent (within the last month) use of investigational drugs;

22. History of drug abuse and/or alcoholism;

23. Pregnant or nursing women and women of childbearing potential not using a medically approved means of contraception ( urinary pregnancy test at screening);

24. Previous participation in this study (i.e. having been allocated a randomised treatment number);

25. Patients deprived of their freedom by a judicial or administrative decision;

26. Minors, adults under guardianship;

27. Persons in medical or social establishments;

28. Patients in emergency situations

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tiotropium 0.625 mcg/puff

• Tiotropium 1.25 mcg/puff

• Tiotropium 2.5 mcg/puff

• Tiotropium 5 mcg/puff

• Placebo solution

• Tiotropium-18 lactose powder

• Placebo lactose powder

• Tiotropium 10 mcg/puff

Device:
• Respimat

• Handihaler

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced expiratory volume in one second (FEV1) with emphasis on the last two hours of the 24-hour dosing interval (trough FEV1)		last two hours of the 24-hour dosing interval	No
Secondary	Forced expiratory volume in one second (FEV1)		during the first four hours post dose	No
Secondary	Forced Vital Capacity (FVC)		during first four hours post dose	No
Secondary	Pharmacokinetic evaluation: 2-hours urine sampling pre- and post-dose (10 patients per group)		before and after last drug administration at day7,14 and 21.	No
Secondary	Chronic obstructive pulmonary disease symptom scores, physician's global evaluation, sleep question and use of rescue medication		3 weeks treatment period	No
Secondary	Changes in ECG, pulse rate (PR) and blood pressure (BP) from the pre-dose values recorded on test day		Day 0, day 7, day 14, day 21	No
Secondary	Changes in ECG, physical examination, haematology and biochemistry recorded before and after the trial		Screening, 24 to 28 days after treatment	No
Secondary	Occurrence of adverse events		up to 28 days	No

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