SYNERGY: Swiss studY for the Treatment of COPD Patients With the Free combiNation of indacatERol and GlYcopyrroniumbromide.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01699685
• Collaborator: (none)
• Enrollment: 79
• Locations: 11
• Arms: 2
• Duration (Months): 19
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The study purpose is to evaluate the effect of QAB149

• NVA237 vs. QAB149 on static lung hyperinflation.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease: COPD	Drug: QAB149; Drug: Placebo; Drug: NVA237	Phase 3

Detailed Description

This is a multicenter, randomized, double-blinded, single-dose, cross-over, placebo-controlled study. The primary endpoint was chosen to demonstrate the superiority of a single-dose of the combined inhalation vs. the mono inhalation regarding the Inspiratory Capacity (IC) peak value. A total of 78 patients will be randomized to complete two visits with two single doses of treatment. Patients will be randomized in a cross-over manner. Treatment visits will be separated by a study medication wash-out period.Treatments will be administered in a blinded fashion.

The patients will be male and female patients, ≥40 years of age, with a documented diagnosis of moderate or severe COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and >10-pack years history of smoking, FEV1 <80% and ≥30% of the predicted normal value.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Single-dose Study to Assess the Effect of the QAB149 and NVA237 Combination Versus QAB149 Alone on Inspiratory Capacity in Patients With Moderate or Severe COPD.
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sequence A Patients will inhale QAB149 (capsule form in blister packs) + Placebo via Novartis Concept 1 SDDPI	Drug: QAB149; Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI; Drug: Placebo; Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI
Active Comparator: Sequence B Patients will inhale QAB149 plus NVA237 (capsule form in blister packs) via Novartis Concept 1 SDDPI	Drug: QAB149; Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI; Drug: NVA237; Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI

Outcome Measures

Primary Outcome Measures

1. Inspiratory Capacity (IC) Peak Value [Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours]

   IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min).

Secondary Outcome Measures

1. Forced Expiratory Volume in One Second (FEV1) [Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours]

   FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations

2. Inspiratory Capacity (IC) [within 4h after dosing]

   During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose

3. Forced Volume Capacity (FVC) [Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours]

   FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time

4. Total Lung Capacity (TLC) [Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours]

   TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose

5. Airway Resistance (Raw) [Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours]

   Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Male and female patients, ≥40 years of age, with a documented diagnosis of moderate or severe COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and >10-pack year history of smoking

• FEV1 <80% and ≥30% of the predicted normal value who have signed an informed consent form prior to the initiation of any study-related procedure

Exclusion criteria:

• No COPD exacerbations within 6 weeks prior to dosing

• No concomitant lung disease such as asthma

• Nno requirement for long term oxygen treatment or history of lung reduction surgery

• No medical conditions that would interfere with the performance of spirometry

• No other medical condition that in the opinion of the investigator may cause the patient to be unsuitable for completion of the study or place the patient at potential risk form being in the study e.g. uncontrolled hypertension or unstable ischemic heart disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Faltigberg-Wald	ZH	Switzerland	8639
2	Novartis Investigative Site	Barmelweid		Switzerland	5017
3	Novartis Investigative Site	Basel		Switzerland	4031
4	Novartis Investigative Site	Bern		Switzerland	3010
5	Novartis Investigative Site	Bern		Switzerland	3013
6	Novartis Investigative Site	Crans-Montana		Switzerland	3963
7	Novartis Investigative Site	Lausanne		Switzerland	1011
8	Novartis Investigative Site	Locarno		Switzerland	6600
9	Novartis Investigative Site	Lugano		Switzerland	6900
10	Novartis Investigative Site	St. Gallen		Switzerland	9007
11	Novartis Investigative Site	Walenstadtberg		Switzerland	8881

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Corinne Wild, PhD, Novartis Pharmaceuticals
• Study Chair: Corinne Wild, PhD, Novartis Pharmaceuticals
• Principal Investigator: Martin Brutsche, Prof. Dr. med., Kantonsspital St. Gallen, Switzerland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01699685
• Other Study ID Numbers: CNVA237ACH01; 2012-002362-13
• First Posted: Oct 4, 2012
• Last Update Posted: Feb 9, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Moderate to severe COPD patients are included; NVA; QAB
• Additional relevant MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Glycopyrrolate

Study Results

Participant Flow

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
Period Title: Period 1
STARTED	39	39
Safety Population	39	38
Full Analysis Population (FAS)	38	38
COMPLETED	36	36
NOT COMPLETED	3	3
Period Title: Period 1
STARTED	36	36
COMPLETED	35	36
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Sequence A	Sequence B	Total
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo	Total of all reporting groups
Overall Participants	39	38	77
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.62 (9.247)	64.18 (7.447)	64.91 (8.383)
Sex: Female, Male (Count of Participants)
Female	14 35.9%	17 44.7%	31 40.3%
Male	25 64.1%	21 55.3%	46 59.7%

Outcome Measures

1. Primary Outcome

Title	Inspiratory Capacity (IC) Peak Value
Description	IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min).
Time Frame	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
Measure Participants	38	38
Day 0 (n=38, 38)	2.87 (0.808)	2.94 (0.777)
Day 6 (n=36, 36)	2.99 (0.856)	2.85 (0.707)

2. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1)
Description	FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations
Time Frame	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
Measure Participants	38	38
Day (0) 30 min post-dose	1.49 (0.442)	1.57 (0.505)
Day (0) 1 hour post-dose	1.50 (0.440)	1.60 (0.506)
Day (0) 2 hour post-dose	1.51 (0.437)	1.60 (0.506)
Day (0) 3 hour post-dose	1.53 (0.430)	1.59 (0.500)
Day (0) 4 hour post-dose	1.53 (0.434)	1.60 (0.492)
Day (6) 30 min post-dose	1.59 (0.437)	1.52 (0.473)
Day (6) 1 hour post-dose	1.63 (0.465)	1.53 (0.463)
Day (6) 2 hour post-dose	1.66 (0.462)	1.55 (0.476)
Day (6) 3 hour post-dose	1.65 (0.455)	1.56 (0.470)
Day (6) 4 hour post-dose	1.64 (0.473)	1.56 (0.459)

3. Secondary Outcome

Title	Inspiratory Capacity (IC)
Description	During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose
Time Frame	within 4h after dosing

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
Measure Participants	38	38
Day (0) 30 min post-dose	2.67 (0.771)	2.75 (0.751)
Day (0) 1 hour post-dose	2.67 (0.799)	2.79 (0.774)
Day (0) 2 hour post-dose	2.69 (0.803)	2.71 (0.709)
Day (0) 3 hour post-dose	2.74 (0.811)	2.69 (0.800)
Day (0) 4 hour post-dose	2.74 (0.823)	2.74 (0.754)
Day (6) 30 min post-dose	2.79 (0.826)	2.40 (0.724)
Day (6) 1 hour post-dose	2.80 (0.810)	2.72 (0.759)
Day (6) 2 hour post-dose	2.86 (0.846)	2.74 (0.689)
Day (6) 3 hour post-dose	2.83 (0.841)	2.69 (0.719)
Day (6) 4 hour post-dose	2.85 (0.799)	2.68 (0.699)

4. Secondary Outcome

Title	Forced Volume Capacity (FVC)
Description	FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time
Time Frame	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
Measure Participants	38	38
Day (0) 30 min post-dose	2.98 (0.917)	3.00 (0.839)
Day (0) 1 hour post-dose	3.00 (0.966)	3.02 (0.846)
Day (0) 2 hour post-dose	3.01 (0.947)	3.04 (0.862)
Day (0) 3 hour post-dose	3.08 (0.946)	3.04 (0.872)
Day (0) 4 hour post-dose	3.07 (0.968)	3.07 (0.852)
Day (6) 30 min post-dose	3.19 (1.002)	2.96 (0.788)
Day (6) 1 hour post-dose	3.25 (1.047)	2.97 (0.807)
Day (6) 2 hour post-dose	3.29 (1.018)	2.99 (0.754)
Day (6) 3 hour post-dose	3.32 (1.003)	2.98 (0.794)
Day (6) 4 hour post-dose	3.30 (1.012)	2.96 (0.797)

5. Secondary Outcome

Title	Total Lung Capacity (TLC)
Description	TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose
Time Frame	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
Measure Participants	38	38
Day (0) 30 min post-dose	7.20 (1.587)	6.81 (1.144)
Day (0) 1 hour post-dose	7.17 (1.559)	6.79 (1.197)
Day (0) 2 hour post-dose	7.06 (1.658)	6.81 (1.190)
Day (0) 3 hour post-dose	7.14 (1.662)	6.82 (1.198)
Day (0) 4 hour post-dose	7.21 (1.608)	6.78 (1.247)
Day (6) 30 min post-dose	7.20 (1.664)	6.79 (1.243)
Day (6) 1 hour post-dose	7.12 (1.576)	6.80 (1.312)
Day (6) 2 hour post-dose	7.21 (1.641)	6.80 (1.213)
Day (6) 3 hour post-dose	7.23 (1.561)	6.81 (1.304)
Day (6) 4 hour post-dose	7.30 (1.691)	6.93 (1.376)

6. Secondary Outcome

Title	Airway Resistance (Raw)
Description	Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes
Time Frame	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)	QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
Measure Participants	38	38
Day (0) 30 min post-dose	5.13 (2.243)	4.74 (1.810)
Day (0) 1 hour post-dose	5.19 (2.561)	4.61 (1.881)
Day (0) 2 hour post-dose	5.21 (2.496)	4.43 (1.849)
Day (0) 3 hour post-dose	5.07 (2.528)	4.53 (1.748)
Day (0) 4 hour post-dose	5.18 (2.535)	4.48 (1.866)
Day (6) 30 min post-dose	4.73 (2.540)	5.18 (2.130)
Day (6) 1 hour post-dose	4.47 (2.323)	4.97 (1.861)
Day (6) 2 hour post-dose	4.31 (2.119)	4.71 (1.822)
Day (6) 3 hour post-dose	4.30 (2.161)	4.77 (1.989)
Day (6) 4 hour post-dose	4.30 (2.170)	4.78 (1.939)

Adverse Events

Arm/Group Title	Sequence A		Sequence B
Arm/Group Description	QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)		QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo
All Cause Mortality
	Sequence A		Sequence B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sequence A		Sequence B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Sequence A		Sequence B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/39 (12.8%)		3/38 (7.9%)
Infections and infestations
Nasopharyngitis	1/39 (2.6%)		0/38 (0%)
Investigations
Forced expiratory volume decreased	1/39 (2.6%)		1/38 (2.6%)
Inspiratory capacity decreased	1/39 (2.6%)		0/38 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/39 (0%)		1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/39 (2.6%)		1/38 (2.6%)
Lung disorder	1/39 (2.6%)		0/38 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.