Clinical trial NCT01613326: Efficacy, Safety, and Tolerability of NVA237 Compared to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A 12-week Treatment, Randomized, Blinded, Double-dummy, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of NVA237 (50 µg o.d.) Compared to Tiotropium (18 µg o.d.) in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-06-07
Enrollment: 657
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 compared the efficacy and safety of NVA237 with tiotropium in patients with moderate to severe COPD. Tiotropium belongs to the same drug class as NVA237.

Detailed description: This was a randomized, blinded, double-dummy, parallel-group 12-week study to assess the efficacy, safety, and tolerability of NVA237 (50 μg o.d.) compared to tiotropium (18 μg o.d.) in patients with chronic obstructive pulmonary disease (COPD).

Eligibility criteria: Inclusion Criteria:

* Patients with moderate to severe stable COPD (Stage II or Stage III) according to the current GOLD Guidelines (GOLD 2010).
* Patients with a post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) ≥ 30% and \< 80% of the predicted normal, and a post-bronchodilator FEV1/ Forced Vital Capacity (FVC) \< 0.70 at screening
* Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack/day x 10 yrs, or ½ pack/day x 20 yrs).
* Symptomatic 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.

Exclusion Criteria:

* Pregnant or nursing (lactating) women
* Patients who, in the judgment of the investigator, or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition before Visit 1.
* Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (BPH patients who are stable on treatment can be considered).
* Patients receiving medications in the classes listed in the protocol as prohibited.

Other protocol-defined inclusion/exclusion criteria apply and can be found in the study protocol

Primary outcomes:
measure: Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment (Non-inferiority Analysis)
timeFrame: Week 12
Secondary outcomes:
measure: Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment (Analysis of Superiority)
timeFrame: Week 12
measure: Transition Dyspnea Index (TDI) Focal Score After 4 Weeks and 12 Weeks of Treatment
timeFrame: Weeks 4 and 12
measure: St. George's Respiratory Questionnaire Total Score After 12 Weeks of Treatment
timeFrame: Week 12
measure: Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Used Over the 12 Week Treatment
timeFrame: Baseline and Day 1 to Week 12
measure: Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 1 and Week 4
timeFrame: Day 1 and Week 4
measure: Peak Forced Expiratory Volume in 1 Second (FEV1) During 5 Min to 4 Hours Post-dose, at Day 1 and Week 12
timeFrame: 5 min to 4 hours post-dose at Day 1 and Week 12
measure: Inspiratory Capacity (IC) at Each Time-point, by Visit
timeFrame: (25 min, 1 h 55 min, 3 h 55 min, 23 h 40 min Day 1), (-20 min, 25 min, 23 h 40 min Week 4),(-20 min, 25 min, 1 h 55 min, 3 h 55 min, 23 h 40 min Week 12)
measure: Forced Expiratory Volume in 1 Second (FEV1) at Each Time-point by Visit
timeFrame: (5,15,30 min, 1, 2,3,4 h, 23h 15 min and 23h 45 min postdose of Day 1), (-45, -15 min predose, 5,15,30 min, 1h, 23h 15 min and 23h 45 min postdose of Week 4), (-45, -15 min predose, 5,15,30 min, 1, 2, 3,4 h, 23h 15 min and 23h 45 min postdose of Week 12)
measure: Forced Vital Capacity (FVC) at Each Time-point by Visit
timeFrame: (5,15,30 min, 1, 2,3,4 h, 23h 15 min and 23h 45 min postdose of Day 1), (-45, -15 min predose, 5,15,30 min, 1h, 23h 15 min and 23h 45 min postdose of Week 4), (-45, -15 min predose, 5,15,30 min, 1, 2, 3,4 h, 23h 15 min and 23h 45 min postdose of Week 12)
measure: Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (5 Min-4 h) Post-dose
timeFrame: Day 1 and week 12
measure: Event Free Rate at Weeks 4, 8 and 12 After Treatment
timeFrame: Weeks 4, 8 and 12
measure: Mean Daily, Daytime and Nighttime (Combined) Symptom Scores Over the 12 Week Treatment Period
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Gatineau
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Mirabel
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: St-Charles-Borromée
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sisak
country: Croatia
facility: Novartis Investigative Site
city: Zagreb
country: Croatia
facility: Novartis Investigative Site
city: Zagreb
country: Croatia
facility: Novartis Investigative Site
city: Cvikov
country: Czech Republic
facility: Novartis Investigative Site
city: Liberec
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 10
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 4
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 6
country: Czech Republic
facility: Novartis Investigative Site
city: Rudna
country: Czech Republic
facility: Novartis Investigative Site
city: Teplice
country: Czech Republic
facility: Novartis Investigative Site
city: Zatec
country: Czech Republic
facility: Novartis Investigative Site
city: Paide
country: Estonia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Beuvry
country: France
facility: Novartis Investigative Site
city: Lyon cedex 04
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Rüdersdorf
country: Germany
facility: Novartis Investigative Site
city: Wiesbaden
country: Germany
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guntur
country: India
facility: Novartis Investigative Site
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Coimbatore
country: India
facility: Novartis Investigative Site
state: Tamil Nadu
city: Chennai - Tamil Nadu
country: India
facility: Novartis Investigative Site
city: Bucheon-Si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi-Do
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Daugavpils
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Alytus
country: Lithuania
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
city: Klaipeda
country: Lithuania
facility: Novartis Investigative Site
city: Klaipeda
country: Lithuania
facility: Novartis Investigative Site
city: Utena
country: Lithuania
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Lipa City
country: Philippines
facility: Novartis Investigative Site
state: Batangas
city: Bulacan
country: Philippines
facility: Novartis Investigative Site
city: Manila
country: Philippines
facility: Novartis Investigative Site
city: Quezon City
country: Philippines
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Katowice
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
city: Gatesville
country: South Africa
facility: Novartis Investigative Site
city: Chia-Yi
country: Taiwan
facility: Novartis Investigative Site
city: Chiayi
country: Taiwan
facility: Novartis Investigative Site
city: Niaosong Township
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei County
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Chapman KR, Beeh KM, Beier J, Bateman ED, D'Urzo A, Nutbrown R, Henley M, Chen H, Overend T, D'Andrea P. A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study. BMC Pulm Med. 2014 Jan 17;14:4. doi: 10.1186/1471-2466-14-4.