Long Term Safety and Tolerability of QVA149 Versus Tiotropium in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

A 52-week Treatment, Multi-center, Randomized, Open Label, Parallel Group Study to Assess the Long Term Safety and Tolerability of QVA149 (110 Mcg Indacaterol / 50 Mcg Glycopyrrolate o.d.) Using Tiotropium (18 Mcg o.d.) as an Active Control in Japanese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

This is a 52-week treatment, multi-center, randomized, open label, parallel group study to assess the long term safety and tolerability of once-daily QVA149 (indacaterol and NVA237 ([glycopyrronium bromide]) using tiotropium as an active control in Japanese patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: QVA149; Drug: Tiotropium

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan, 010-0933
    • Novartis Investigative Site
  • Fukuoka, Japan, 812-0033
    • Novartis Investigative Site
  • Fukuoka, Japan, 811-0213
    • Novartis Investigative Site
  • Fukuoka, Japan, 815-8588
    • Novartis Investigative Site
  • Kochi, Japan, 780-8077
    • Novartis Investigative Site
  • Osaka, Japan, 558-8558
    • Novartis Investigative Site
  • Wakayama, Japan, 641-8510
    • Novartis Investigative Site
  • Aichi
    • Anjo, Aichi, Japan, 446-8602
      • Novartis Investigative Site
    • Nagoya, Aichi, Japan, 457-8511
      • Novartis Investigative Site
    • Nishio-city, Aichi, Japan, 445-8510
      • Novartis Investigative Site
  • Fukuoka
    • Kasuga-city, Fukuoka, Japan, 816-0813
      • Novartis Investigative Site
    • Kitakyushu, Fukuoka, Japan, 820-0052
      • Novartis Investigative Site
    • Kurume, Fukuoka, Japan, 830-0011
      • Novartis Investigative Site
    • Yanagawa, Fukuoka, Japan, 832-0059
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 070-8644
      • Novartis Investigative Site
    • Obihiro, Hokkaido, Japan, 080-0805
      • Novartis Investigative Site
    • Sapporo-city, Hokkaido, Japan, 060-8648
      • Novartis Investigative Site
  • Hyogo
    • Himeji-city, Hyogo, Japan, 672-8064
      • Novartis Investigative Site
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8610
      • Novartis Investigative Site
  • Kagawa
    • Takamatsu, Kagawa, Japan, 760-8538
      • Novartis Investigative Site
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 210-0852
      • Novartis Investigative Site
    • Yokohama, Kanagawa, Japan, 236-0051
      • Novartis Investigative Site
  • Kumamoto
    • Koshi-city, Kumamoto, Japan, 861-1196
      • Novartis Investigative Site
  • Mie
    • Matsusaka-city, Mie, Japan, 515-8544
      • Novartis Investigative Site
  • Nagano
    • Ueda, Nagano, Japan, 386-8610
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 545-8586
      • Novartis Investigative Site
    • Osakasayama, Osaka, Japan, 589-0022
      • Novartis Investigative Site
    • Takatsuki, Osaka, Japan, 569-1192
      • Novartis Investigative Site
    • Toyonaka, Osaka, Japan, 560-8552
      • Novartis Investigative Site
  • Saitama
    • Kawaguhi-city, Saitama, Japan, 333-0833
      • Novartis Investigative Site
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-8525
      • Novartis Investigative Site
  • Tokyo
    • Fuchu, Tokyo, Japan, 183-8524
      • Novartis Investigative Site
    • Meguro, Tokyo, Japan, 152-8902
      • Novartis Investigative Site
  • Yamagata
    • Yamagata city, Yamagata, Japan, 990-8533
      • Novartis Investigative Site
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-0241
      • 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:

• Patients with moderate to severe stable COPD (Stage II or Stage III) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines 2008.
• Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.)
• Patients with post-bronchodilator forced expiratory volume in one second (FEV1) ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (FVC) < 0.7 at Visit 2.

Exclusion Criteria:

• Pregnant women or nursing mothers or women of child-bearing potential not using an acceptable method of contraception
• Patients requiring long term oxygen therapy
• Patients who have had a lower respiratory tract infection within 4 weeks prior to Visit 1
• Patients with concomitant pulmonary disease
• Patients with a history of asthma
• Any patient with history of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years
• Patients with a history of certain cardiovascular comorbid conditions
• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
• Patients in the active phase of a supervised pulmonary rehabilitation program
• Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to anticholinergic agents, long and short acting beta-2 agonists, sympathomimetic amines

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QVA149; QVA149 110/50 μg once a day (o.d)	Drug: QVA149; QVA149 (110 μg indacaterol / 50 μg glycopyrronium o.d.), delivered via Concept1
Active Comparator: Tiotropium; tiotropium 18 μg o.d.	Drug: Tiotropium; Tiotropium (18 μg o.d.), delivered via Handihaler®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death	An AE was the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event was not considered to be related to study drug. Study drug includes the investigational drug under evaluation and the comparator drug or placebo that was given during any phase of the study. Adverse events starting on or after the time of the first inhalation of study drug were classified as a treatment emergent adverse event.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period	Clinically notable hematology values were: hemoglobin - male <11.5g/dL, female <9.5 g/dL; hematocrit - male <37%, female <32%; white cell count - <2800µL or >16000µL; platelets - <7.5 10*4/µL or >70.0 10*4/µL	52 weeks
Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period	Clinically notable biochemistry values were: total protein - <4.0 g/dL or >9.5 g/dL; albumin <2.5 g/dL; bilirubin (total) >1.9 mg/dL; BUN >27 mg/dL; creatinine >1.99 mg/dL; AST >3 x ULN U/L; ALT >3 x ULN U/L; ALP >3 x ULN U/L; y-GTP >3 x ULN U/L; sodium <125 mEq/L or >160 mEq/L; potassium <3.0 mEq/L or >6.0 mEq/L; glucose <51.0 mg/dL or >180.0 mg/dL	52 weeks
Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period	Clinically notable vital sign values were: pulse rate - low, <40 bpm or <=50 bpm and decrease from baseline >=15bpm; pulse rate high, >130 bpm or >=120bpm and increase from baseline >=15 bpm. Systolic blood pressure - low, <75 mmHg or <=90 mmHg and decrease from baseline >=20 mmHg; high, >200 mmHg or >=180 mmHg and increase from baseline >=20 mmHg. Diastolic blood pressure - low, <40 mmHg or <=50 mmHg and decrease from baseline >=15 mmHg; high, >115 mmHg or >=105 mmHg and increase from baseline >=15 mmHg.	52 weeks
Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period	Clinically notable change from baseline was an increase from baseline of 30 or greater milliseconds (ms).	52 weeks
Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline	Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FEV1 value on Day 1 (Week 1).	Weeks 3, 6, 12, 24, 36, 52
Change in Pre-dose Forced Vital Capacity (FVC) From Baseline	Pre-dose FVC is defined as the average of the measurements at 45 and 15 min pre-dose. Baseline is defined as the pre-dose FVC value on Day 1 (Week 1).	Weeks 3, 6, 12, 24, 36, 52

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: January 25, 2011
• First Submitted That Met QC Criteria: January 26, 2011
• First Posted (Estimate): January 28, 2011

Study Record Updates

• Last Update Posted (Estimate): December 27, 2013
• Last Update Submitted That Met QC Criteria: December 3, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: COPD; indacaterol; QVA149; NVA237; combination bronchodilator
• 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; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide
• Other Study ID Numbers: CQVA149A1301