A randomized, double-blind, placebo-controlled, multi-center, two-period crossover study to investigate the bronchodilatory effect of 50µg NVA237 inhaled once daily in patients with Chronic Obstructive Pulmonary Disease (COPD)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-006849-28-DE
• Date of registration: 21/01/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, double-blind, placebo-controlled, multi-center, two-period crossover study to investigate the bronchodilatory effect of 50µg NVA237 inhaled once daily in patients with Chronic Obstructive Pulmonary Disease (COPD)
• Scientific title: A randomized, double-blind, placebo-controlled, multi-center, two-period crossover study to investigate the bronchodilatory effect of 50µg NVA237 inhaled once daily in patients with Chronic Obstructive Pulmonary Disease (COPD)
• Date of first enrolment: 10/03/2009
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-006849-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

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 mild, moderate or severe COPD according to the GOLD Guidelines (2007).
3. Current or ex-smokers who have smoking history of at least 10 pack years.
4. Patients with a post-bronchodilator FEV1 =30% of the predicted normal, and post-bronchodilator FEV1/FVC = 0.7 at Visit 1.
5. FEV1 increase by 5% or more in bronchial reversibility test with 40 µg ipratropiumbromide

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 (1) 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 (2) have past 6 weeks from surgical bilateral oophorectomy with or without hysterectomy OR (3) are using one of the following acceptable methods of contraception: surgical sterilization (e.g. bilateral tubal ligation) and the double barrier method consisting of diaphragma plus condome. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. NOTE: Reliable contraception must 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 screening. Patients who develop a respiratory tract infection during the screening period (up to Day -1) 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, have a clinically relevant laboratory abnormality or a clinically significant condition which would compromise patient safety or compliance. Patients with the following medical conditions are specifically excluded from the study: unstable ischemic heart disease, left ventricular failure, long term prednisone therapy, history of myocardial infarction, relevant cardiac arrhythmia
6. Patients who have contraindications for anti-muscarinic drugs such as narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment.
7. Patients with a history of asthma indicated by (but not limited to) onset of symptoms prior to the age of 40 years.
8. Patients who have shown an untoward reaction to inhaled anticholinergic agents.
9. Patients with a history of long QT syndrome or whose QTc measured at screening (Fridericia method) is prolonged (>450 ms for males or >470 ms for females).
10. Treatments for COPD and allied conditions: the following medications should not be used between screening and end of study. The minimum washout prior to treatment periods is specified below where applicable:
The long acting anticholinergic agent tiotropium:7 days.
Short acting anticholinergics: 8 h
Patients taking fixed combinations of beta2-agonists and inhaled corticosteroids should be switched to the corresponding dose of inhaled corticosteroid and rescue on-demand short acting beta2-agonists medication. The minimum washout period of 48 hours for long acting ?2-agonists should be adhered to.
Long-acting beta2-agonists: 48 h
Short acting beta2-agonists (other than those prescribed in the study): 6 h
Theophylline (any formulation): 7 days
Combinations of inhaled anticholinergics and ß agonists: 24 hours
11. Patients who need the following treatments unle

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Mild, moderate or severe Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 9.1 Level: LLT Classification code 10010952 Term: COPD

Intervention(s)

Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: glycopyrrolate
CAS Number: 596-51-0
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main Objective: Investigate the bronchodilatory efficacy of 50µg NVA237 over 24 hours following 14 days treatment when compared to placebo.

Primary end point(s): Investigate the bronchodilatory efficacy of 50µg NVA237 over 24 hours following 14 days treatment when compared to placebo.

Secondary Objective: •Investigate the peak bronchodilator effect of NVA237
•Investigate the trough bronchodilator effect at the end of the 24 h assessment interval
•Investigate the bronchodilator effect on the first and second portion of the 24 h assessment interval (0h – 12h and 12h – 24 h after 14 days dosing)
•Investigate the bronchodilator effects on NVA237 on Day 7 (in analogy to those on Day 14)
•Investigate the safety and tolerability of 50µg NVA237 in COPD patients

Secondary ID(s)

CNVA237A2207