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

Phase 2

Completed

• Conditions: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: Tiotropium 10 mcg/puff; Drug: Tiotropium 0.625 mcg/puff; Drug: Tiotropium 5 mcg/puff; Drug: Tiotropium-18 lactose powder; Drug: Tiotropium 2.5 mcg/puff; Drug: Placebo solution; Drug: Placebo lactose powder; Drug: Tiotropium 1.25 mcg/puff; Device: Respimat; Device: Handihaler

• Registration Number: NCT02175342
• Lead Sponsor: Boehringer Ingelheim

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 1998-03-01
• Primary Completion: 1999-04-01
• Study First Submitted: 2014-06-24
• Study First Submitted QC: 2014-06-25
• Study First Posted: 2014-06-26
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-29
• Last Update Posted: 2025-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 202

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tiotropium-20 Respimat	Tiotropium 10 mcg/puff	Two puffs of tiotropium inhalation solution from a Respimat device, 10 mcg/puff
Tiotropium-1.25 Respimat	Tiotropium 0.625 mcg/puff	Two puffs of tiotropium inhalation solution from a Respimat device, 0.625 mcg/puff
Tiotropium-5 Respimat	Respimat	Two puffs of tiotropium inhalation solution from a Respimat device, 2.5 mcg/puff
Tiotropium-10 Respimat	Tiotropium 5 mcg/puff	Two puffs of tiotropium inhalation solution from a Respimat device, 5 mcg/puff
Tiotropium-20 Respimat	Respimat	Two puffs of tiotropium inhalation solution from a Respimat device, 10 mcg/puff
Tiotropium-18 lactose powder Handihaler	Tiotropium-18 lactose powder	-
Tiotropium-18 lactose powder Handihaler	Handihaler	-
Tiotropium-2.5 Respimat	Respimat	Two puffs of tiotropium inhalation solution from a Respimat device, 1.25 mcg/puff
Tiotropium-5 Respimat	Tiotropium 2.5 mcg/puff	Two puffs of tiotropium inhalation solution from a Respimat device, 2.5 mcg/puff
Placebo Respimat	Placebo solution	-
Placebo lactose powder Handihaler	Placebo lactose powder	-
Tiotropium-1.25 Respimat	Respimat	Two puffs of tiotropium inhalation solution from a Respimat device, 0.625 mcg/puff
Placebo Respimat	Respimat	-
Tiotropium-2.5 Respimat	Tiotropium 1.25 mcg/puff	Two puffs of tiotropium inhalation solution from a Respimat device, 1.25 mcg/puff
Tiotropium-10 Respimat	Respimat	Two puffs of tiotropium inhalation solution from a Respimat device, 5 mcg/puff
Placebo lactose powder Handihaler	Handihaler	-

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
Forced expiratory volume in one second (FEV1)	during the first four hours post dose
Chronic obstructive pulmonary disease symptom scores, physician's global evaluation, sleep question and use of rescue medication	3 weeks treatment period
Forced Vital Capacity (FVC)	during first four hours post dose
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.
Changes in ECG, physical examination, haematology and biochemistry recorded before and after the trial	Screening, 24 to 28 days after treatment
Occurrence of adverse events	up to 28 days
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