A randomized, double-blind, placebo-controlled, 4 period incomplete block cross-over, multi-center, multiple dose (7 days) dose-ranging study to assess the efficacy and safety of 4 doses of NVA237 in patients with stable Chronic Obstructive Pulmonary Disease (COPD), compared to seven days treatment with tiotropium (18µg once daily, open label) as an active control.

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2007-000642-13-FR
• Date of registration: 16/05/2007
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, double-blind, placebo-controlled, 4 period incomplete block cross-over, multi-center, multiple dose (7 days) dose-ranging study to assess the efficacy and safety of 4 doses of NVA237 in patients with stable Chronic Obstructive Pulmonary Disease (COPD), compared to seven days treatment with tiotropium (18µg once daily, open label) as an active control.
• Scientific title: A randomized, double-blind, placebo-controlled, 4 period incomplete block cross-over, multi-center, multiple dose (7 days) dose-ranging study to assess the efficacy and safety of 4 doses of NVA237 in patients with stable Chronic Obstructive Pulmonary Disease (COPD), compared to seven days treatment with tiotropium (18µg once daily, open label) as an active control.
• Date of first enrolment: 12/07/2007
• Target sample size: 73
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000642-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, France

Key inclusion & exclusion criteria

Inclusion criteria:
•Male or female adults aged = 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
•Patients with moderate to severe COPD according to the GOLD Guidelines (2006).
•Patients who have smoking history of at least 10 pack years.
•Patients with a post-bronchodilator FEV1 =30 % and < 80 % of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at Visit 2.

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:
•Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test) and females of childbearing potential who do not use a reliable contraceptive method.
•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 during the run-in period (between Visit 1 and Visit 3).
•Patients who have had respiratory tract infection within 6 weeks prior to Visit 1.
•Patients who develop a respiratory tract infection during the screening period (up to Visit 3) must discontinue from the trial, but will be permitted to re-enroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection).
•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, cancers, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia (all), narrow-angle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment.
•Patients with a history of asthma indicated by (but not limited to):
a) Blood eosinophil count > 400/mm3
b) Onset of symptoms prior to age 40 years.
•Patients contraindicated for tiotropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents.
•Patients with a history of long QT syndrome or whose QTc measured at Visit 1 is prolonged (>440 ms for males or >460 for females).
•Patients with a history of untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
•Treatments for COPD and allied conditions : the following medications should not be used between Visits 1 and 18. The minimum washout prior to Visit 2 is specified below :
The long acting anticholinergic agent tiotropium :7 days.
Short acting anticholinergics : 8 h
Fixed combinations of beta 2-agonists and inhaled corticosteroids : 48 h - Patients taking fixed combinations of corticosteroid/beta-agonist prior to Visit 1 should be transferred to the same dose of steroid contained in the fixed combination and on-demand rescue medication for a period of 2 weeks prior to Visit 2.
Long-acting beta 2-agonists : 48 h
Short acting beta 2-agonists (other than those prescribed in the study): 6 hours
Theophylline (any formulation): 7 days
Combinations of inhaled anticholinergics and beta agonists: 24 hours
Patients taking fixed combinations of corticosteroid/beta-agonist prior to Visit 1 should be transferred to the same dose of steroid contained in the fixed combination and on-demand rescue medication for a period of 2 weeks prior to Visit 2.
•Patients who need the following treatments for COPD and allied conditions unless they have been stabilized for at least one month prior to visit 1 :
•Inhaled or nasal corticosteroids
•Cromoglycate, nedocromil, ketotifen in recommended and constant doses and dose regimens
•Patients taking beta blocking agents
•Patients unable to use a dry powder inhaler (Single Dose Dry Powder Inhaler or HandiHaler® type) device or a pMDI (rescue medication), perform spirometry measurements or complete a patient log.
•Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of Visit 1, whichever is longer.
•History of hypersensitivity to any of the st

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

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 9.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease

Intervention(s)

Product Name: glycopyrrolate
Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
CAS Number: 596-51-0
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 12.5-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Product Name: glycopyrrolate
Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
CAS Number: 596-51-0
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Product Name: glycopyrrolate
Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
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

Product Name: glycopyrrolate
Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
CAS Number: 596-51-0
Current Sponsor code: NVA237
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Trade Name: Spiriva
Product Name: Tiotropium bromide
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: tiotropium bromide
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Primary end point(s): The primary efficacy variable is 'trough FEV1' at Day7.
The trough in FEV1 is defined as the mean of two measurements at 23h15 mins and 23h45 mins post dosing.
The baseline measurement is defined as the mean of the FEV1 values taken in the clinic at 45 mins and 15 mins prior to dosing at Visit 3.

Secondary Objective: To explore additional efficacy, safety, and tolerability of the four doses of NVA237 in comparison with placebo delivered by the Single Dose Powder Inhaler (SDDPI) and with tiotropium (18 micrograms) delivered by Handihaler® as an active control

Main Objective: To evaluate the bronchodilatory efficacy of NVA237 in patients with stable COPD in terms of trough FEV1 (mean of 23h 15 min & 23h 45 min post dose) following 7 days of treatment, by comparing four doses of NVA237 (12.5, 25, 50 & 100 micrograms o.d.) with placebo delivered by the single Dose Dry Powder Inhaler (SDDPI).

Secondary ID(s)

CNVA237A2205

2007-000642-13-BE