A multi-center, randomized, double-blind, placebocontrolled, two-period cross-over study to assess the effect of 50 µg inhaled NVA237 on exercise endurance in patients with moderate to severe COPD - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-018597-20-IT
• Date of registration: 10/09/2010
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS FARMA
• Public title: A multi-center, randomized, double-blind, placebocontrolled, two-period cross-over study to assess the effect of 50 µg inhaled NVA237 on exercise endurance in patients with moderate to severe COPD - ND
• Scientific title: A multi-center, randomized, double-blind, placebocontrolled, two-period cross-over study to assess the effect of 50 µg inhaled NVA237 on exercise endurance in patients with moderate to severe COPD - ND
• Date of first enrolment: 13/09/2010
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018597-20
• 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, Italy, United Kingdom

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 moderate to severe stable COPD (clinical diagnosis in compliance with GOLD Guidelines 2008).
3. Current or ex-smokers who have a 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 =35% and < 70% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 during screening.
(Post refers to 30 min after inhalation of 80 µg ipratropium bromide).
5. Increase in FEV1 from Pre-bronchodilator to Post-bronchodilator assessment of at least 5%.
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 or of child-bearing potential except for the cases listed into protocol. - Patients who have had a COPD exacerbation in the 6 weeks prior to Visit 1 or between V. 1 and V. 4.- Patients who have had a lower respiratory tract infection in the 6 weeks prior to V. 1.- Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia.- Patients with resting (5 min) oxygen SaO2 saturation on room air of < 85%.- Patients with a Wmax value <20 W at V. 2.-Patients, whose exercise endurance time at sub-maximal workload is above 25 min at baseline; - Patients with contraindications (see example into Protocol) to cardiopulmonary exercise testing ;- Patients involved in the active phase of a supervised Pulmonary Rehabilitation Program.- Patients who have a clinically relevant laboratory abnormality or a clinically significant condition such the ones described into the Protocol as example; - Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency.- Patients with concomitant pulmonary disease, e.g., pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis.- Patients with any history of asthma or with allergic rhinitis who use H1 antagonists or intranasal corticosteroids intermittently are to be excluded. Treatment with a stable dose is permitted (constant dose for at least 1 month prior to V. 2).- Patients with a history of long QT syndrome or whose QTc is prolonged at screening. - Patients who have a clinically significant abnormality on the screening or baseline ECG who in the judgement of the investigator would be at potential risk if enrolled into the study. - Patients contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the class drugs described into the Protocol, included, for example, anti-cholinergic agents, long- and short-acting ß2-agonists, sympathomimetic amines; - Treatments for COPD and allied conditions: the medications described into the Protocol should not be used between V. 1 and V. 4 and then through the subsequent course of the study. Further to this, into the Protocol, is specified the minimum washout prior to V. 2.- Patients who need the following treatments for COPD and allied conditions (e.g. allergic rhinitis) unless they have been stabilized as follows: Inhaled corticosteroids in recommended and constant doses and dose regimens (previously given as either part of a fixed dose combination of LABA+ICS or ICS as monotherapy) for at least 1 month prior to V. 2, Intranasal corticosteroids in recommended and constant doses and dose regimens for at least 1 month prior to V. 2, H1 antagonists in recommended and constant doses and dose regimens for at least 5 days prior to V. 2;- Other excluded medications: Leukotriene antagonists (7 days prior to V. 2), Cromoglycate, nedocromil, ketotifen (7 days prior to V. 2), Intramuscular glucocorticosteroid e.g. Kenalog: unless discontinued 3 months prior to V. 2, Parenteral or oral glucocorticosteroids unless discontinued 1 month prior to V. 2;- Patients unable to use a dry powder inhaler device or pressurized rescue medication) or unable to use an electronic patient diary;- Patients who are known to be unreliable or noncompliant or with any condition or prior or present treatment rendering the patient not eligible for the study;- Use of other invest. drugs at the time of enrollment, or within 30 days or 5 halflive

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: SOC Classification code 10038738

Intervention(s)

Product Name: Glycopyrrolate
Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
CAS Number: 596510
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: To determine the effect of 50 µg NVA237 compared with matching placebo inhaled once
daily on exercise tolerance as measured by exercise endurance time during a sub-maximal
constant-load cycle ergometry test (SMETT) after three weeks of treatment.

Primary end point(s): Primary PD endpoint is exercise endurance at week three.

Secondary Objective: Key sec.obj.:To determine the effect of 50 µgNVA237 compared with plac.on isotime inspiratory capacity during SMETT after 3weeks of treatment.
• To determine the effect of 50µg NVA237 compared with plac.on inspiratory capacity at rest and at peak during SMETT after 3 weeks of treatment.• To determine the effect of 50 µg NVA237 compared with plac.on peak and trough (i.e.24 h post dose) FEV1 after 3 weeks of treatment.
• To evaluate the effects of 50 µg NVA237 compared to plac.on Slow Vital Capacity, Forced Vital Capacity, Specific Airway Conductance and Total
Lung Capacity after 3 weeks of treatment.• To evaluate the effect of 50 µg NVA237 compared to placebo on exertional dyspnea during SMETT after 3weeks treatment.• To evaluate the effect of 50 µg NVA237 compared to placebo on leg discomfort during SMETT after3 weeks treatment.-To determine the effect of a single dose on treat.Day1 of 50µgNVA237 compared with plac.on exercise tolerance as measured byExer.EnduranceTime duringSMETT

Secondary ID(s)

2010-018597-20-GB

CNVA237A2310