Clinical trial NCT01119950: Efficacy and Safety of NVA237 in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Randomized, Double-blind, Placebo-controlled, 2-period, Cross-over Study to Assess the Efficacy and Safety of Differing Doses of NVA237 Administered Either Once Daily or Twice Daily, in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-05-10
Enrollment: 388
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study was designed to investigate the efficacy and safety of NVA237, a long-acting muscarinic antagonist, in patients with moderate to severe COPD.


Eligibility criteria: Inclusion Criteria:

* Male and female patients age 40 years or more
* Diagnosis of Chronic Obstructive Lung Disease (COPD) (moderate to severe as classified by the Global Initiative for COPD (GOLD) Guidelines, 2008
* Smoking history of at least 10 pack-years
* Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) \<80% and ≥30% of the predicted normal value
* Post-bronchodilator FEV1/Forced Vital Capacity (FVC) \<0.7
* Symptomatic patients, according to daily electronic diary data between visit 2 (Day -8) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to visit 3

Exclusion Criteria:

* Patients who have had a COPD exacerbation requiring systemic corticosteroids and/or antibiotics and/or hospitalization in the 6 weeks prior to the first visit
* Patients who have had a respiratory tract infection within 4 weeks prior to the first visit
* Patients with concomitant pulmonary disease
* Patients with diabetes Type I or uncontrolled diabetes Type II
* Any patient with lung cancer or a history of lung cancer
* Patients with a history of certain cardiovascular co-morbid conditions
* Patients with a history of asthma or a blood eosinophil count \>600/mm3 or onset of symptoms prior to 40 years
* Patients with eczema, known high IgE levels or a known positive skin prick test
* Patients participating in the active phase of a pulmonary rehabilitation programme
* Patients contraindicated for the treatment with anticholinergics, long and short-acting beta-2 agonists or sympathomimetic amines
* Patients with a history of alpha-1 anti-trypsin deficiency
* Patients on long term oxygen therapy (\>15hr per day)
* Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Maximal Response of Incremental Once Daily and Twice Daily Doses of NVA237 That Each Dose Achieves in Relation to the Maximal Effect of NVA237 on Trough Forced Expiratory Volume in One Second at Day 28
timeFrame: Day 28
Secondary outcomes:
measure: Trough Forced Expiratory Volume in One Second for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237
timeFrame: day 28
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment
timeFrame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
measure: Forced Expiratory Volume in One Second AUC 0-24 Hours for Once and Twice Daily Regimens of NVA237 for the Same Total Daily Dose of NVA237, After 28 Days of Treatment
timeFrame: -25 min,-15 min (predose); 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours) on Day 28
timeFrame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours at Day 28 of Treatment
timeFrame: 12 hours on day 28
measure: Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second at Day 28 of Treatment
timeFrame: day 28
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Vital Capacity at Day 28 of Treatment
timeFrame: day 28
measure: Percentage of the Maximal Response of NVA237 Doses on Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14
timeFrame: Days 1, 7 and 14
measure: Percentage of the Maximal Effect of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment
timeFrame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment
timeFrame: 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14
timeFrame: at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment
timeFrame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment
timeFrame: 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14
measure: Percentage of the Maximal Response of NVA237 Doses on Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment
timeFrame: Days 1 and 14
measure: Percentage of the Maximal Response of NVA237 Doses on Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment
timeFrame: Days 1, 7, and 14
measure: Percentage of the Maximal Response of NVA237 Doses on Trough Forced Vital Capacity on Days 1, 7 and 14
timeFrame: Days 1, 7 and 14
measure: Mean Daily Use of Rescue Medication by Treatment at Different Time Points
timeFrame: Baseline, Weeks 1, 2, 3 and 4
Other outcomes:
measure: Trough Forced Expiratory Volume in One Second by Treatment at Day 28
timeFrame: Day 28
measure: Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours at Day 28 of Treatment
timeFrame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
measure: Forced Expiratory Volume in One Second Area Under the Curve at Different Time Points (0-4 Hours, 0-8 Hours, 0-12 Hours, 12-24 Hours)
timeFrame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on day 28
measure: Forced Expiratory Volume in One Second at 12 Hours on Day 28 of Treatment
timeFrame: 12 hours on day 28
measure: Peak Forced Expiratory Volume in One Second at Day 28 of Treatment
timeFrame: 25 min , 15 min pre-dose, 5 min, 15 min, 1 , 2 ,3 , 4 , 6 , 8 , 10 hours , 11 hour 55 min and 14 hour post-dose on day 28
measure: Trough Forced Vital Capacity After 28 Days of Treatment
timeFrame: 23 hours 15 mins and 23 hours 45 mins post-dose on Day 28
measure: Trough Forced Expiratory Volume in One Second at Days 1, 7 and 14
timeFrame: 23 hours 15 mins and 23 hours 45 mins post-dose on Days 1, 7 and 14
measure: Forced Expiratory Volume in One Second Area Under the Curve 0-24 Hours on Days 1 and 14 of Treatment
timeFrame: 5 min, 15 min, 1,2,3,4,6,8,10 hours, 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on days 1 and 14
measure: Forced Expiratory Volume in One Second Area Under the Curve 0-4 Hours on Days 1, 7 and 14 of Treatment
timeFrame: 5 min,15 min, 1,2,3,4 hours (postdose) on Days 1, 7 and 14
measure: Forced Expiratory Volume in One Second of Area Under the Curve 0-8 Hours Days 1, 7, and 14
timeFrame: at 5 min,15 min, 1,2,3,4,6,8 hours (postdose) on days 1, 7 and 14
measure: Forced Expiratory Volume in One Second Area Under the Curve 0-12 Hours at Day 1 and 14 of Treatment
timeFrame: 5 min,15 min, 1,2,3,4,6,8,10 hours, 11h 55 min (postdose) on days 1 and 14
measure: Forced Expiratory Volume in One Second of Area Under the Curve 12-24 Hours Over Days 1, and 14 of Treatment
timeFrame: 11 hours 55 min, 14,20,22 hours; 23 hours 15 min, 23 hours 45 min (postdose) on Days 1 and 14
measure: Forced Expiratory Volume in One Second at 12 Hours on Days 1 and 14 of Treatment
timeFrame: Days 1 and 14
measure: Peak Forced Expiratory Volume in One Second on Days 1, 7 and 14 of Treatment
timeFrame: Days 1, 7, and 14
measure: Trough Forced Vital Capacity on Days 1, 7 and 14
timeFrame: Days 1, 7 and 14
Locations:
city: Anniston
country: United States
facility: Novartis Investigative Site
state: Alabama
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Torrance
country: United States
facility: Novartis Investigative Site
state: California
city: Denver
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Antwerpen
country: Belgium
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
city: Jambes
country: Belgium
facility: Novartis Investigative site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Balassagyarmat
country: Hungary
facility: Novartis Investigative Site
city: Balatonfured
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Torokbalint
country: Hungary
facility: Novartis Investigative Site
city: Almelo
country: Netherlands
facility: Novartis Investigative Site
city: Eindhoven
country: Netherlands
facility: Novartis Investigative Site
city: Harderwijk
country: Netherlands
facility: Novartis Investigative Site
city: Heerlen
country: Netherlands
facility: Novartis Investigative Site
city: Helmond
country: Netherlands
facility: Novartis Investigative Site
city: Veldhoven
country: Netherlands
facility: Novartis Investigative Site
city: Zutphen
country: Netherlands
facility: Novartis Investigative Site
city: Izabelin
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Alicante
country: Spain
facility: Novartis Investigative Site
city: La Coruña
country: Spain
facility: Novartis Investigative Site
city: Ponferrada
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Arievich H, Overend T, Renard D, Gibbs M, Alagappan V, Looby M, Banerji D. A novel model-based approach for dose determination of glycopyrronium bromide in COPD. BMC Pulm Med. 2012 Dec 8;12:74. doi: 10.1186/1471-2466-12-74.