Long Term Safety and Tolerability of NVA237 Versus Tiotropium in Japanese Patients (GLOW4)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
NVA237
Tiotropium
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, NVA237
Eligibility Criteria
Inclusion Criteria:
- Patients with moderate to severe stable COPD (Stage II or Stage III) according to the Gold Guideline 2008.
- Current or ex-smokers who have a smoking history of at least 10 pack years.
- Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and postbronchodilator FEV1/FVC < 0.7 at Visit 2 (day -7)
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 6 weeks prior to Visit 1
- Patients with concomitant pulmonary disease
- Patients with a history of asthma
- Any patient with lung cancer or a history of lung cancer
- 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 tiotropium or ipratropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents
- Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
NVA237
Tiotropium
Arm Description
50µg once daily
18µg once daily
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events, Serious Adverse Events or Death
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Secondary Outcome Measures
Change in Pre-dose FEV1 From Baseline
Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Change in Pre-dose FVC From Baseline
Pre-dose FVC is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation
Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required. Participants who withdraw from the study and do not experience a moderate or severe exacerbation are censored at the date of withdrawal. Participants who complete the study and do not experience a moderate or severe exacerbation are censored at the completion visit date.
Number of Patients With Moderate or Severe COPD Exacerbations
Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required.
Change in St. George Respiratory Questionnaire From Baseline
SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period
Patients recorded rescue medication use in a paper patient diary. If a patient required the use of salbutamol as rescue medication due to an increase in COPD symptoms, the number of inhalations (puffs) taken was recorded in the patient diary.
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
Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole 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
Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint 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.
Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period
Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).
Full Information
NCT ID
NCT01119937
First Posted
May 5, 2010
Last Updated
December 12, 2012
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01119937
Brief Title
Long Term Safety and Tolerability of NVA237 Versus Tiotropium in Japanese Patients
Acronym
GLOW4
Official Title
A 52-week Treatment, Multi-center, Randomized, Open Label, Parallel Group Study to Assess the Long Term Safety and Tolerability of NVA237 (50µg o.d.) Using Tiotropium (18µg o.d.) as an Active Control in Japanese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
Study Type
Interventional
2. Study Status
Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
This is a 52-week, multi-center, randomized, open label, parallel group study to assess the long term safety and tolerability of once-daily NVA237, using tiotropium as an active control, in Japanese patients with moderate to severe chronic obstructive pulmonary disease (COPD) .
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
COPD, NVA237
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
211 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NVA237
Arm Type
Experimental
Arm Description
50µg once daily
Arm Title
Tiotropium
Arm Type
Experimental
Arm Description
18µg once daily
Intervention Type
Drug
Intervention Name(s)
NVA237
Intervention Description
50µg capsules for inhalation, delivered via a single dose dry powder inhaler (Concept 1®)
Intervention Type
Drug
Intervention Name(s)
Tiotropium
Intervention Description
18µg capsules for inhalation, delivered via HandiHaler®
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events, Serious Adverse Events or Death
Description
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Change in Pre-dose FEV1 From Baseline
Description
Pre-dose FEV1 is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Time Frame
Weeks 12, 24, 36 and 52
Title
Change in Pre-dose FVC From Baseline
Description
Pre-dose FVC is defined as the average of the measurements at 45 and 15 minutes pre-dose.
Time Frame
Weeks 12, 24, 36 and 52
Title
Time From Randomization Until the Start of the First Moderate or Severe COPD Exacerbation
Description
Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required. Participants who withdraw from the study and do not experience a moderate or severe exacerbation are censored at the date of withdrawal. Participants who complete the study and do not experience a moderate or severe exacerbation are censored at the completion visit date.
Time Frame
52 weeks
Title
Number of Patients With Moderate or Severe COPD Exacerbations
Description
Moderate COPD exacerbations were defined as: worsening of 2 or more of the following major symptoms for at least 2 consecutive days - dyspnea, sputum volume and sputum purulence; OR a worsening of any 1 major symptom with any 1 of the following minor symptoms for at least 2 consecutive days - sore throat, colds, fever without other cause, increased cough or increased wheeze, requiring treatment with systemic glucocorticosteroids or antibiotics or both. Severe COPD exacerbations were defined as: conditions for Moderate COPD exacerbation and hospitalization was required.
Time Frame
52 weeks
Title
Change in St. George Respiratory Questionnaire From Baseline
Description
SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life.
Time Frame
Weeks 12, 24, 36, 52
Title
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication Over the Whole Treatment Period
Description
Patients recorded rescue medication use in a paper patient diary. If a patient required the use of salbutamol as rescue medication due to an increase in COPD symptoms, the number of inhalations (puffs) taken was recorded in the patient diary.
Time Frame
52 weeks
Title
Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period
Description
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
Time Frame
52 weeks
Title
Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period
Description
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
Time Frame
52 weeks
Title
Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period
Description
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.
Time Frame
52 weeks
Title
Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period
Description
Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with moderate to severe stable COPD (Stage II or Stage III) according to the Gold Guideline 2008.
Current or ex-smokers who have a smoking history of at least 10 pack years.
Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and postbronchodilator FEV1/FVC < 0.7 at Visit 2 (day -7)
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 6 weeks prior to Visit 1
Patients with concomitant pulmonary disease
Patients with a history of asthma
Any patient with lung cancer or a history of lung cancer
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 tiotropium or ipratropium treatment or who have shown an untoward reaction to inhaled anticholinergic agents
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Iizuka
State/Province
Fukuoka
ZIP/Postal Code
820-8505
Country
Japan
Facility Name
Novartis Investigative Site
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
802-0083
Country
Japan
Facility Name
Novartis Investigative Site
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
820-0052
Country
Japan
Facility Name
Novartis Investigative Site
City
Kurume
State/Province
Fukuoka
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
Novartis Investigative Site
City
Onojo
State/Province
Fukuoka
ZIP/Postal Code
816-0931
Country
Japan
Facility Name
Novartis Investigative Site
City
Yanagawa
State/Province
Fukuoka
ZIP/Postal Code
832-0059
Country
Japan
Facility Name
Novartis Investigative Site
City
Asahikawa
State/Province
Hokkaido
ZIP/Postal Code
070-8644
Country
Japan
Facility Name
Novartis Investigative Site
City
Obihiro
State/Province
Hokkaido
ZIP/Postal Code
080-0805
Country
Japan
Facility Name
Novartis Investigative Site
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Novartis Investigative Site
City
Himeji-city
State/Province
Hyogo
ZIP/Postal Code
672-8064
Country
Japan
Facility Name
Novartis Investigative Site
City
Takarazuka
State/Province
Hyogo
ZIP/Postal Code
665-0827
Country
Japan
Facility Name
Novartis Investigative Site
City
Yabu
State/Province
Hyogo
ZIP/Postal Code
667-8555
Country
Japan
Facility Name
Novartis Investigative Site
City
Inashiki-gun
State/Province
Ibaraki
ZIP/Postal Code
300-0395
Country
Japan
Facility Name
Novartis Investigative Site
City
Naka-gun
State/Province
Ibaraki
ZIP/Postal Code
319-1113
Country
Japan
Facility Name
Novartis Investigative Site
City
Sashima-gun
State/Province
Ibaraki
ZIP/Postal Code
306-0433
Country
Japan
Facility Name
Novartis Investigative Site
City
Morioka
State/Province
Iwate
ZIP/Postal Code
020-0055
Country
Japan
Facility Name
Novartis Investigative Site
City
Kawasaki
State/Province
Kanagawa
ZIP/Postal Code
210-0852
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
232-0021
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
236-0051
Country
Japan
Facility Name
Novartis Investigative Site
City
Uji
State/Province
Kyoto
ZIP/Postal Code
611-0042
Country
Japan
Facility Name
Novartis Investigative Site
City
Matsusaka-city
State/Province
Mie
ZIP/Postal Code
515-8544
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
981-8563
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagaoka-City
State/Province
Niigata
ZIP/Postal Code
940-2085
Country
Japan
Facility Name
Novartis Investigative Site
City
Nagaoka
State/Province
Niigata
ZIP/Postal Code
940-8653
Country
Japan
Facility Name
Novartis Investigative Site
City
Kasaoka
State/Province
Okayama
ZIP/Postal Code
714-0081
Country
Japan
Facility Name
Novartis Investigative Site
City
Tsuyama
State/Province
Okayama
ZIP/Postal Code
708-0841
Country
Japan
Facility Name
Novartis Investigative Site
City
Osakasayama
State/Province
Osaka
ZIP/Postal Code
589-0022
Country
Japan
Facility Name
Novartis Investigative Site
City
Sakai
State/Province
Osaka
ZIP/Postal Code
591-8555
Country
Japan
Facility Name
Novartis Investigative Site
City
Takatsuki
State/Province
Osaka
ZIP/Postal Code
569-1096
Country
Japan
Facility Name
Novartis Investigative Site
City
Shimotsuka-gun
State/Province
Tochigi
ZIP/Postal Code
321-0293
Country
Japan
Facility Name
Novartis Investigative Site
City
Bunkyo-ku
State/Province
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
Novartis Investigative Site
City
Nakano-ku
State/Province
Tokyo
ZIP/Postal Code
164-0012
Country
Japan
Facility Name
Novartis Investigative Site
City
Ohta-ku
State/Province
Tokyo
ZIP/Postal Code
140-0063
Country
Japan
Facility Name
Novartis Investigative Site
City
Yamagata city
State/Province
Yamagata
ZIP/Postal Code
990-8533
Country
Japan
Facility Name
Novartis Investigative Site
City
Ube
State/Province
Yamaguchi
ZIP/Postal Code
755-0241
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka
ZIP/Postal Code
812-0033
Country
Japan
Facility Name
Novartis Investigative Site
City
Kochi
ZIP/Postal Code
780-8077
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
530-0012
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
545-8586
Country
Japan
Facility Name
Novartis Investigative Site
City
Saitama
ZIP/Postal Code
337-0012
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
Long Term Safety and Tolerability of NVA237 Versus Tiotropium in Japanese Patients
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