A randomized, open-label, multicenter, two-period crossover study to evaluate the 24 hour bronchodilator profile of Tiotropium Bromide Respimat® administered once daily versus twice daily in patients with Chronic Obstructive Pulmonary Disease (COPD)

• Conditions: Chronic Obstructive Pulmonary Disease (COPD); MedDRA version: 9.1Level: LLTClassification code 10010952Term: COPD

• Registration Number: EUCTR2008-006305-16-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-12-16
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

1. Male or female adults aged =40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
2. Patients with moderate to severe COPD (Stage II or Stage III) according to the GOLD Guidelines 2007.
3. Current or ex-smokers who have smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.)
4. Patients with a post-bronchodilator FEV1 =30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at Visit 1 and Visit 3

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
2. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m, OR have past 6 weeks from surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception:
• surgical sterilization (e.g., bilateral tubal ligation),
• hormonal contraception (implantable, patch, oral), and copper coated IUD.
• At the discretion of the investigator, total abstinence is acceptable in cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. NOTE: Reliable contraception should be maintained throughout the study
3. Patients requiring oxygen therapy on a daily basis for chronic hypoxemia, or who have been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 3.
4. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1. Patients who develop a respiratory tract infection or COPD exacerbations during the screening period (up to Visit 4) will not be eligible, but will be permitted to be re-screened at a later date (at least 6 weeks after the resolution of the respiratory tract infection).
5. Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to):
• unstable ischemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding stable AF)
• long term prednisone therapy (defined as =10 mg daily for at least 1 month prior to Visit 1)
• history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
• narrow-angle glaucoma
• symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention
• uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state
• any condition which might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study
6. Patients with a history of asthma indicated by (but not limited to) onset of symptoms prior to age 40 years.
7. Patients contraindicated for tiotropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents.
8. Patients with a history of untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
9. Patients with a history of long QT syndrome or whose QTc measured at Visit 1 (Fridericia method) is prolonged (>450 ms for males or >470 for females).
10. Treatments for COPD and allied conditions: the following medications should not be used between Visits 1

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •Compare the bronchodilator profile over 24 hours of tiotropium bromide administered either twice daily (2.5µg b.i.d.) or once daily (5µg q.d.) following 14 days treatment, measured in terms of 24h FEV1 AUC;Secondary Objective: •Explore the bronchodilator efficacy of once daily versus twice daily dosing with tiotropium bromide at various time points following 14 days treatment, and on the first day of treatment.;Primary end point(s): The primary objective is to compare the bronchodilator profile over 24 hours of tiotropium bromide administered either twice daily (2.5µg b.i.d.) or once daily (5µg q.d.) following 14 days treatment, measured in terms of 24 h FEV1 AUC