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

• ClinicalTrials.gov Identifier: NCT01285492
• Recruitment Status: Completed
• First Posted: January 28, 2011
• Results First Posted: November 7, 2013
• Last Update Posted: December 27, 2013
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: QVA149; Drug: Tiotropium	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: January 2011
• Actual Primary Completion Date: September 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Death [ Time Frame: 52 weeks ]
   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.

Secondary Outcome Measures :

1. Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period [ Time Frame: 52 weeks ]
   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
2. Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Time-point Over the Treatment Period [ Time Frame: 52 weeks ]
   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
3. Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Time-point Over the Whole Treatment Period [ Time Frame: 52 weeks ]
   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.
4. Number of Patients With Newly Occurring or Worsening Clinically Notable Fridericia's QTc Values at Any Time-point Over the Whole Treatment Period [ Time Frame: 52 weeks ]
   Clinically notable change from baseline was an increase from baseline of 30 or greater milliseconds (ms).
5. Change in Pre-dose Forced Expiratory Volume in One Second (FEV1) From Baseline [ Time Frame: Weeks 3, 6, 12, 24, 36, 52 ]
   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).
6. Change in Pre-dose Forced Vital Capacity (FVC) From Baseline [ Time Frame: Weeks 3, 6, 12, 24, 36, 52 ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Japan

Novartis Investigative Site

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

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

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

Himeji-city, Hyogo, Japan, 672-8064

Novartis Investigative Site

Kanazawa, Ishikawa, Japan, 920-8610

Novartis Investigative Site

Takamatsu, Kagawa, Japan, 760-8538

Novartis Investigative Site

Kawasaki, Kanagawa, Japan, 210-0852

Novartis Investigative Site

Yokohama, Kanagawa, Japan, 236-0051

Novartis Investigative Site

Koshi-city, Kumamoto, Japan, 861-1196

Novartis Investigative Site

Matsusaka-city, Mie, Japan, 515-8544

Novartis Investigative Site

Ueda, Nagano, Japan, 386-8610

Novartis Investigative Site

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

Kawaguhi-city, Saitama, Japan, 333-0833

Novartis Investigative Site

Hamamatsu, Shizuoka, Japan, 430-8525

Novartis Investigative Site

Fuchu, Tokyo, Japan, 183-8524

Novartis Investigative Site

Meguro, Tokyo, Japan, 152-8902

Novartis Investigative Site

Yamagata city, Yamagata, Japan, 990-8533

Novartis Investigative Site

Ube, Yamaguchi, Japan, 755-0241

Novartis Investigative Site

Akita, Japan, 010-0933

Novartis Investigative Site

Fukuoka, Japan, 811-0213

Novartis Investigative Site

Fukuoka, Japan, 812-0033

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

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01285492
• Other Study ID Numbers: CQVA149A1301
• First Posted: January 28, 2011
• Results First Posted: November 7, 2013
• Last Update Posted: December 27, 2013
• Last Verified: December 2013

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

COPD; QVA149; NVA237; indacaterol; combination bronchodilator

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Tiotropium Bromide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Parasympatholytics; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action