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

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.

The study purpose is to evaluate the effect of QAB149

• NVA237 vs. QAB149 on static lung hyperinflation.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease: COPD
• Intervention / Treatment: Drug: QAB149; Drug: Placebo; Drug: NVA237

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 Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 3

Contacts and Locations

Study Locations

• Switzerland
  • Barmelweid, Switzerland, 5017
    • Novartis Investigative Site
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Bern, Switzerland, 3013
    • Novartis Investigative Site
  • Crans-Montana, Switzerland, 3963
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
  • Locarno, Switzerland, 6600
    • Novartis Investigative Site
  • Lugano, Switzerland, 6900
    • Novartis Investigative Site
  • St. Gallen, Switzerland, 9007
    • Novartis Investigative Site
  • Walenstadtberg, Switzerland, 8881
    • Novartis Investigative Site
  • ZH
    • Faltigberg-Wald, ZH, Switzerland, 8639
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inspiratory Capacity (IC) Peak Value	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).	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1)	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	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Inspiratory Capacity (IC)	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	within 4h after dosing
Forced Volume Capacity (FVC)	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	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Total Lung Capacity (TLC)	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	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Airway Resistance (Raw)	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	Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• Salomon J, Stolz D, Domenighetti G, Frey JG, Turk AJ, Azzola A, Sigrist T, Fitting JW, Schmidt U, Geiser T, Wild C, Kostikas K, Clemens A, Brutsche M. Indacaterol and glycopyrronium versus indacaterol on body plethysmography measurements in COPD-a randomised controlled study. Respir Res. 2017 Jan 11;18(1):13. doi: 10.1186/s12931-016-0498-1.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: September 28, 2012
• First Submitted That Met QC Criteria: October 1, 2012
• First Posted (ESTIMATE): October 4, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2016
• Last Update Submitted That Met QC Criteria: January 11, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: NVA; Moderate to severe COPD patients are included; QAB
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Glycopyrrolate
• Other Study ID Numbers: CNVA237ACH01; 2012-002362-13 (EUDRACT_NUMBER)