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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2010-018597-20-GB
• Date of registration: 17/06/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A multi-center, randomized, double-blind, placebo- controlled, two-period cross-over study to assess the effect of 50µg inhaled NVA237 on exercise endurance in patients with moderate to severe COPD - n/a
• Scientific title: A multi-center, randomized, double-blind, placebo- controlled, two-period cross-over study to assess the effect of 50µg inhaled NVA237 on exercise endurance in patients with moderate to severe COPD - n/a
• Date of first enrolment: 09/08/2010
• 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: yes 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 =40% and < 70% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 during screening.
(Post refers to the highest post-bronchodilator value 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:
1. Pregnant women or nursing mothers.
2. Women of child-bearing potential (WOCBP), as defined by the protocol OR surgical bilateral oophorectomy with or without hysterectomy at least 6 months prior to screening Visit 1 OR are using one or more of the acceptable methods of contraception defined in the protocol.
3. Patients who have had a COPD exacerbation (whether hospitalized or not) in the 6 weeks
prior to Visit 1 or between Visit 1 and Visit 4.
4. Patients who have had a lower respiratory tract infection in the 6 weeks prior to Visit 1.Patients who develop a lower respiratory tract infection during the screening period (up to Visit 4) will not be eligible, but will be permitted to be re-screened at least 6 weeks after the resolution of the lower respiratory tract infection.
5. Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia.
6. Patients with resting (5 min) oxygen SaO2 saturation on room air of < 85%
7. Patients with a Wmax value <20 W (as determined by the incremental cycle endurance
test) at Visit 2.
8. Patients, whose exercise endurance time at sub-maximal workload is above 25 min at baseline
9. Patients with contraindications (acc. to ATS/ACCP Statement on cardiopulmonary exercise testing issued 2003) to cardiopulmonary exercise testing including (but not limited to) those defined in the protocol.
10. Patients involved in active phase of a supervised Pulmonary Rehabilitation Program.
11. Patients who have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) those defined in the protocol.
12. Patients with known history & diagnosis of alpha-1 antitrypsin deficiency.
13. Patients with concomitant pulmonary disease, e.g., pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active) or clinically significant bronchiectasis.
14. Patients with any history of asthma (as diagnosed by GINA guidelines).
15. Patients 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 5 days prior to visit 2 & 1mth prior to visit 2 respectively).
16. Patients with history of long QT syndrome or whose QTc is prolonged (>450 ms for males and (>470 ms females) at screening.
17. Patients who have clinically significant abnormality on the screening or baseline ECG.
18. Patients contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the inhaled drugs, drugs of a similar class or any component thereof listed in the protocol.
19. Treatments for COPD & allied conditions: the listed medications in the protocol should not be used between Visit 1 and Visit 4 and then through the subsequent course of the study.
20. Patients who need the treatments for COPD and allied conditions (e.g. allergic rhinitis) as listed in the protocol unless they have been stabilized as defined in the protocol.
21. Other excluded medications as defined in the protocol.
22. Patients unable to use a dry powder inhaler (SDDPI) device or pressurized MDI (rescue medication).
23. Patients unable to use an electronic patient diary.
24. Patients who are, in the opinion of the investigator known to be unreliable or noncompliant, or with any condition or prior or present treatment rendering the patient not eligible for the study.
25. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-li

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

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 13.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: Glycopyrrolate
Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596510
Current Sponsor code: NVA237
Other descriptive name: Glycopyrrolate
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): 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

Secondary Objective: To determine the effect of 50 µg NVA237 compared with placebo on isotime inspiratory capacity (IC) during SMETT after three weeks of treatment.

Other:
• determine effect of 50 µg NVA237 compared with placebo on inspiratory capacity (IC) at rest & at peak during SMETT after 3wks of treatment.
• determine effect of 50 µg NVA237 compared with placebo on peak & trough (i.e. 24 h post dose) FEV1 after 3wks of treatment.
• evaluate effects of 50 µg NVA237 compared to placebo on Slow Vital Capacity, Forced Vital Capacity, Specific Airway Conductance & Total Lung Capacity after 3wks of treatment.
• evaluate effect of 50 µg NVA237 compared to placebo on exertional dyspnea during SMETT after 3wks treatment.
• evaluate effect of 50 µg NVA237 compared to placebo on leg discomfort during SMETT after 3wks treatment.
• determine effect of single dose on treatment Day 1 of 50 µg NVA237 compared with placebo on exercise tolerance as measured by exercise endurance time during
SMETT.

Secondary ID(s)

CNVA237A2310