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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285492
• Other study ID #: CQVA149A1301
• Status: Completed
• Phase: Phase 3
• First received: January 25, 2011
• Last updated: December 3, 2013
• Start date: January 2011
• Est. completion date: September 2012

Study information

• Verified date: December 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 (110 µg indacaterol / 50 µg glycopyrronium o.d.), delivered via Concept1
• Tiotropium
Tiotropium (18 µg o.d.), delivered via Handihaler®

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Akita
Japan	Novartis Investigative Site	Anjo	Aichi
Japan	Novartis Investigative Site	Asahikawa	Hokkaido
Japan	Novartis Investigative Site	Fuchu	Tokyo
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Hamamatsu	Shizuoka
Japan	Novartis Investigative Site	Himeji-city	Hyogo
Japan	Novartis Investigative Site	Kanazawa	Ishikawa
Japan	Novartis Investigative Site	Kasuga-city	Fukuoka
Japan	Novartis Investigative Site	Kawaguhi-city	Saitama
Japan	Novartis Investigative Site	Kawasaki	Kanagawa
Japan	Novartis Investigative Site	Kitakyushu	Fukuoka
Japan	Novartis Investigative Site	Kochi
Japan	Novartis Investigative Site	Koshi-city	Kumamoto
Japan	Novartis Investigative Site	Kurume	Fukuoka
Japan	Novartis Investigative Site	Matsusaka-city	Mie
Japan	Novartis Investigative Site	Meguro	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nishio-city	Aichi
Japan	Novartis Investigative Site	Obihiro	Hokkaido
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Osakasayama	Osaka
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Takamatsu	Kagawa
Japan	Novartis Investigative Site	Takatsuki	Osaka
Japan	Novartis Investigative Site	Toyonaka	Osaka
Japan	Novartis Investigative Site	Ube	Yamaguchi
Japan	Novartis Investigative Site	Ueda	Nagano
Japan	Novartis Investigative Site	Wakayama
Japan	Novartis Investigative Site	Yamagata city	Yamagata
Japan	Novartis Investigative Site	Yanagawa	Fukuoka
Japan	Novartis Investigative Site	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No