Efficacy, safety, and tolerability of NVA237 compared to tiotropium in patients with chronic obstructive pulmonary disease (COPD)

• Register: EUCTR
• Last refreshed on: 4 February 2013
• Main ID: EUCTR2011-000960-93-PL
• Date of registration: 07/05/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Efficacy, safety, and tolerability of NVA237 compared to tiotropium in patients with chronic obstructive pulmonary disease (COPD)
• Scientific 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)
• Date of first enrolment: 20/06/2012
• Target sample size: 660
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000960-93
• 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: no Other: yes Other trial design description: double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Canada, Croatia, Czech Republic, Estonia, Guatemala, India, Korea, Republic of, Latvia, Lithuania, Philippines, Poland, South Africa, Taiwan, Turkey

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria: To be eligible, patients have to fulfill all the 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 FEV1 = 30% and < 80% of the predicted normal, and a post-bronchodilator FEV1/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.

Other protocol-defined inclusion criteria may apply
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 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 330

Exclusion criteria:
1. Pregnant or nursing (lactating) women.
2. 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.
3. 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).
4. Patients receiving medications in the classes listed in the protocol as prohibited.

Other protocol-defined exclusion criteria may apply



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

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 14.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Glycopyrronium bromide
Product Code: NVA237
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: GLYCOPYRRONIUM BROMIDE
CAS Number: 596-51-0
Current Sponsor code: NVA237
Other descriptive name: Glycopyrronium Bromide
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

Trade Name: Spiriva Handihaler
Product Name: Spiriva Handihaler
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TIOTROPIUM BROMIDE
CAS Number: 139404-48-1
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 18-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Trough Forced Expiratory Volume in 1 Second (FEV1)

Secondary Objective: To demonstrate superiority of NVA237 (50 µg o.d.) vs. tiotropium (18 µg o.d.) on trough FEV1 after 12 weeks of treatment in patients with moderate to severe COPD if the primary objective of non-inferiority is reached.

Main Objective: To demonstrate non-inferiority of NVA237 50 µg o.d. versus tiotropium 18 µg o.d. with respect to trough Forced Expiratory Volume in one second (trough FEV1) after 12 weeks (84 days) of treatment in patients with moderate to severe COPD (GOLD, 2010). Trough refers to the mean of FEV1 at 23h 15 mins and 23h 45 mins after the morning dose of study drug.

Timepoint(s) of evaluation of this end point: Timeframe: At 12 weeks

Secondary Outcome(s)

Secondary end point(s): a. Transition Dyspnea Index (TDI) Focal Score
b. The mean change from baseline in the daily number of puffs of rescue medication
c. The mean change from baseline in the daytime number of puffs of rescue medication.
d. The mean change from baseline in the nighttime number of puffs of rescue medication
e. The percentage of ‘days with no rescue use’
f. Mean trough FEV1
g. Mean peak FEV1
h. FEV1
i. Forced Vital Capacity (FVC)
j. Inspiratory Capacity (IC)
k. FEV1 AUC (5min-4h)
l. Percentage of nights with ‘no nighttime awakenings’
m. Percentage of days with ‘no daytime symptoms’
n. Percentage of ‘days able to perform usual daily activities’
o. Symptom scores
p. Time to first moderate /severe COPD exacerbation
q. Rate of moderate / severe COPD exacerbations
r. Safety variables
s. Electrocardiogram (ECG)
t. Vital Signs (Blood pressure and radial pulse)
u. Laboratory Data
v. Quality of Life Assessment with St George’s Respiratory Questionnaire (SGRQ)

Timepoint(s) of evaluation of this end point: a. Timeframe: At 12 weeks
b. c. d. e. Timeframe: Over 12 weeks
f. g. Timeframe: Day 1; Week 4
h. i. j. Timeframe: At individual time-points on Day 1, Week 4 and Week 12
k. Timeframe: Day 1 and Week 12
l. m. n. o. p. q. r. Timeframe: Over 12 weeks
s. Timeframe: Day 1 and Week 12
t. Timeframe: At individual time-points on Days 1, 2, 28,29,84
u. v. Timeframe: 12 weeks

Secondary ID(s)

CNVA237A2314

2011-000960-93-CZ

Source(s) of Monetary Support

Novartis Pharma Service AG