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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tiotropium-1.25 Respimat; Two puffs of tiotropium inhalation solution from a Respimat device, 0.625 mcg/puff	Drug: Tiotropium 0.625 mcg/puff; Device: Respimat
Experimental: Tiotropium-2.5 Respimat; Two puffs of tiotropium inhalation solution from a Respimat device, 1.25 mcg/puff	Device: Respimat; Drug: Tiotropium 1.25 mcg/puff
Experimental: Tiotropium-5 Respimat; Two puffs of tiotropium inhalation solution from a Respimat device, 2.5 mcg/puff	Device: Respimat; Drug: Tiotropium 2.5 mcg/puff
Experimental: Tiotropium-10 Respimat; Two puffs of tiotropium inhalation solution from a Respimat device, 5 mcg/puff	Device: Respimat; Drug: Tiotropium 5 mcg/puff
Experimental: Tiotropium-20 Respimat; Two puffs of tiotropium inhalation solution from a Respimat device, 10 mcg/puff	Device: Respimat; Drug: Tiotropium 10 mcg/puff
Placebo Comparator: Placebo Respimat	Drug: Placebo solution; Device: Respimat
Active Comparator: Tiotropium-18 lactose powder Handihaler	Drug: Tiotropium-18 lactose powder; Device: Handihaler
Placebo Comparator: Placebo lactose powder Handihaler	Device: Handihaler; Drug: Placebo lactose powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Forced expiratory volume in one second (FEV1)	during the first four hours post dose
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.
Chronic obstructive pulmonary disease symptom scores, physician's global evaluation, sleep question and use of rescue medication	3 weeks treatment period
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
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 1998
• Primary Completion (Actual): April 1, 1999

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimated): June 26, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Tiotropium Bromide
• Other Study ID Numbers: 205.127

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency