Clinical trial NCT00929110: 1-year Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Chronic Obstructive Pulmonary Disease (COPD)
Official title: A 52-week Treatment, Randomized, Double-blind, Placebo-controlled, With Open-label Tiotropium, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Glycopyrronium Bromide (NVA237) in Patients With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
NVA237
glycopyrronium bromide
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-06-26
Enrollment: 1066
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to investigate the 1 year efficacy and safety of the 50 µg once daily (od) dose of glycopyrronium bromide (NVA237) in patients with moderate to severe chronic obstructive pulmonary disease.


Eligibility 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 chronic obstructive pulmonary disease (COPD, Stage II or Stage III) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2008.
3. Current or ex-smokers who have a smoking history of at least 10 pack years.
4. Patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 30% and \< 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) \< 0.7 at Visit 2 (Day -14).
5. Patients, according to daily electronic diary data between Visit 2 (Day -14) 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 (Day 1).

Exclusion Criteria:

1. Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
2. Women of child-bearing potential, unless using an approved method of medical or surgical contraception.
3. Patients requiring long term oxygen therapy (\> 15 h a day) 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 (Day -21) or between Visit 1 (Day -21) and Visit 3 (Day 1).
4. Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1 (Day -21).
5. Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition.
6. Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count \> 600/mm\^3 (at Visit 1, Day -21) and onset of symptoms prior to age 40 years.
7. Patients with a history of long QT syndrome or whose QTc measured at Visit 1 (Day -21) (Fridericia method) is prolonged (\> 450 ms for males or \> 470 ms for females.

Other protocol-defined inclusion/exclusion criteria may apply to the study.

Primary outcomes:
measure: Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Transition Dyspnea Index (TDI) at Week 26
timeFrame: Week 26
measure: Health-related Quality of Life (QoL) Assessed With the St. George Respiratory Questionnaire (SGRQ) at Week 52
timeFrame: Week 52
measure: Time to First Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52 (patients with no moderate or severe exacerbations who completed the study were censored at the final visit date, which may have exceeded 52 weeks)
measure: Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication Taken During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52
measure: Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1, Week 26, and Week 52
timeFrame: Day 1, Week 26, and Week 52
measure: Trough Forced Vital Capacity (FVC) at Day 1, Week 12, Week 26, and Week 52
timeFrame: Day 1, Week 12, Week 26, and Week 52
measure: Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
timeFrame: 5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
measure: Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; 1, 2, 3, 4, 6, 8, 10, and 12 Hours; 23 Hours 15 Minutes; and 23 Hours 45 Minutes Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
timeFrame: 5, 15, and 30 minutes; 1, 2, 3, 4, 6, 8, 10, and 12 hours; 23 hours 15 minutes; and 23 hours 45 minutes post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
measure: Forced Expiratory Volume in 1 Second (FEV1) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post Dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
timeFrame: 5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
measure: Forced Vital Capacity (FVC) 5, 15, and 30 Minutes; and 1, 2, 3, and 4 Hours Post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
timeFrame: 5, 15, and 30 minutes; and 1, 2, 3, 4 hours post-dose at Days 1 and 15; and Weeks 5, 9, 12, 16, 20, 26, 34, 42, 50, and 52
measure: Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at Day 1 and Weeks 12, 26, and 52
timeFrame: From 5 minutes to 4 hours post-dose at Day 1 and Weeks 12, 26, and 52
measure: Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose at Day 1 and Weeks 12 and 52
timeFrame: From 5 minutes to 12 hours post-dose at Day 1 and Weeks 12 and 52
measure: Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 23 Hours 45 Minutes and From 12 Hours to 23 Hours 45 Minutes Post-dose at Weeks 12 and 52
timeFrame: From 5 minutes to 23 hours 45 minutes post-dose at Weeks 12 and 52
measure: Number of Moderate or Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) Per Year During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52
measure: Percentage of Patients Who Experienced a Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52
measure: Percentage of Nights With "no Nighttime Awakenings" During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52
measure: Percentage of Days With "no Daytime Symptoms" During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52
measure: Percentage of "Days Able to Perform Usual Daily Activities" During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52
measure: Change From Baseline in the Mean Daily Total Symptom Score During the Study (Baseline to Week 52)
timeFrame: Baseline to Week 52
Other outcomes:
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country: Korea, Republic of
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city: Incheon
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city: Seoul
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country: Mexico
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city: Monterrey
country: Mexico
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city: San Luis Potosi
country: Mexico
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city: Sneek
country: Netherlands
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city: Auckland
country: New Zealand
facility: Novartis Investigator Site
city: Christchurch
country: New Zealand
facility: Novartis Investigator Site
city: Hamilton
country: New Zealand
facility: Novartis Investigator Site
city: Tauranga
country: New Zealand
facility: Novartis Investigator Site
city: Wellington
country: New Zealand
facility: Novartis Investigator Site
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Santiago de Surco
country: Peru
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Bystra
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Ostrow Wielkopolski
country: Poland
facility: Novartis Investigative Site
city: Piekary Slaskic
country: Poland
facility: Novartis Investigative Site
city: Tarnow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Irkutsk
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Smolensk
country: Russian Federation
facility: Novartis Investigative Site
city: Volgograd
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: D'Urzo A, Kerwin E, Overend T, D'Andrea P, Chen H, Goyal P. Once daily glycopyrronium for the treatment of COPD: pooled analysis of the GLOW1 and GLOW2 studies. Curr Med Res Opin. 2014 Mar;30(3):493-508. doi: 10.1185/03007995.2013.858618. Epub 2013 Nov 19.
citation: Kerwin E, Hebert J, Gallagher N, Martin C, Overend T, Alagappan VK, Lu Y, Banerji D. Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study. Eur Respir J. 2012 Nov;40(5):1106-14. doi: 10.1183/09031936.00040712. Epub 2012 Jul 26.