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

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Pulmonary Disease, Chronic Obstructive

Treatments: Device: Handihaler; Drug: Placebo solution; Drug: Tiotropium 1.25 mcg/puff; Drug: Tiotropium-18 lactose powder; Drug: Tiotropium 10 mcg/puff; Drug: Placebo lactose powder; Device: Respimat; Drug: Tiotropium 2.5 mcg/puff; Drug: Tiotropium 0.625 mcg/puff; Drug: Tiotropium 5 mcg/puff

Study type: Interventional

Funder types: Industry

Identifiers

NCT02175342

205.127

Details and patient eligibility

About

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.

Enrollment: 202 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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202 participants in 8 patient groups, including a placebo group

Tiotropium-1.25 Respimat

Experimental group

Description:

Two puffs of tiotropium inhalation solution from a Respimat device, 0.625 mcg/puff

Treatment:

Drug: Tiotropium 0.625 mcg/puff

Device: Respimat

Tiotropium-2.5 Respimat

Experimental group

Description:

Two puffs of tiotropium inhalation solution from a Respimat device, 1.25 mcg/puff

Treatment:

Device: Respimat

Drug: Tiotropium 1.25 mcg/puff

Tiotropium-5 Respimat

Experimental group

Description:

Two puffs of tiotropium inhalation solution from a Respimat device, 2.5 mcg/puff

Treatment:

Drug: Tiotropium 2.5 mcg/puff

Device: Respimat

Tiotropium-10 Respimat

Experimental group

Description:

Two puffs of tiotropium inhalation solution from a Respimat device, 5 mcg/puff

Treatment:

Drug: Tiotropium 5 mcg/puff

Device: Respimat

Tiotropium-20 Respimat

Experimental group

Description:

Two puffs of tiotropium inhalation solution from a Respimat device, 10 mcg/puff

Treatment:

Device: Respimat

Drug: Tiotropium 10 mcg/puff

Placebo Respimat

Placebo Comparator group

Treatment:

Device: Respimat

Drug: Placebo solution

Tiotropium-18 lactose powder Handihaler

Active Comparator group

Treatment:

Drug: Tiotropium-18 lactose powder

Device: Handihaler

Placebo lactose powder Handihaler

Placebo Comparator group

Treatment:

Drug: Placebo lactose powder

Device: Handihaler