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Long Term Safety and Tolerability of NVA237 Versus Tiotropium in Japanese Patients (GLOW4)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01119937
First received: May 5, 2010
Last updated: December 12, 2012
Last verified: November 2012
  Purpose

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) .


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: NVA237
Drug: Tiotropium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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 NVA237 (50µg o.d.) Using Tiotropium (18µg o.d.) as an Active Control in Japanese Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants With Adverse Events, Serious Adverse Events or Death [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Weeks 12, 24, 36 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 12, 24, 36 and 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Weeks 12, 24, 36, 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).


Enrollment: 211
Study Start Date: May 2010
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NVA237
50µg once daily
Drug: NVA237
50µg capsules for inhalation, delivered via a single dose dry powder inhaler (Concept 1®)
Experimental: Tiotropium
18µg once daily
Drug: Tiotropium
18µg capsules for inhalation, delivered via HandiHaler®

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01119937

Locations
Japan
Novartis Investigative Site
Iizuka, Fukuoka, Japan, 820-8505
Novartis Investigative Site
Kitakyushu, Fukuoka, Japan, 802-0083
Novartis Investigative Site
Kitakyushu, Fukuoka, Japan, 820-0052
Novartis Investigative Site
Kurume, Fukuoka, Japan, 830-0011
Novartis Investigative Site
Onojo, Fukuoka, Japan, 816-0931
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, Hokkaido, Japan, 060-8648
Novartis Investigative Site
Himeji-city, Hyogo, Japan, 672-8064
Novartis Investigative Site
Takarazuka, Hyogo, Japan, 665-0827
Novartis Investigative Site
Yabu, Hyogo, Japan, 667-8555
Novartis Investigative Site
Inashiki-gun, Ibaraki, Japan, 300-0395
Novartis Investigative Site
Naka-gun, Ibaraki, Japan, 319-1113
Novartis Investigative Site
Sashima-gun, Ibaraki, Japan, 306-0433
Novartis Investigative Site
Morioka, Iwate, Japan, 020-0055
Novartis Investigative Site
Kawasaki, Kanagawa, Japan, 210-0852
Novartis Investigative Site
Yokohama, Kanagawa, Japan, 232-0021
Novartis Investigative Site
Yokohama, Kanagawa, Japan, 236-0051
Novartis Investigative Site
Uji, Kyoto, Japan, 611-0042
Novartis Investigative Site
Matsusaka-city, Mie, Japan, 515-8544
Novartis Investigative Site
Sendai, Miyagi, Japan, 981-8563
Novartis Investigative Site
Nagaoka, Niigata, Japan, 940-8653
Novartis Investigative Site
Nagaoka-City, Niigata, Japan, 940-2085
Novartis Investigative Site
Kasaoka, Okayama, Japan, 714-0081
Novartis Investigative Site
Tsuyama, Okayama, Japan, 708-0841
Novartis Investigative Site
Osakasayama, Osaka, Japan, 589-0022
Novartis Investigative Site
Sakai, Osaka, Japan, 591-8555
Novartis Investigative Site
Takatsuki, Osaka, Japan, 569-1096
Novartis Investigative Site
Shimotsuka-gun, Tochigi, Japan, 321-0293
Novartis Investigative Site
Bunkyo-ku, Tokyo, Japan, 113-8431
Novartis Investigative Site
Nakano-ku, Tokyo, Japan, 164-0012
Novartis Investigative Site
Ohta-ku, Tokyo, Japan, 140-0063
Novartis Investigative Site
Yamagata city, Yamagata, Japan, 990-8533
Novartis Investigative Site
Ube, Yamaguchi, Japan, 755-0241
Novartis Investigative Site
Fukuoka, Japan, 812-0033
Novartis Investigative Site
Kochi, Japan, 780-8077
Novartis Investigative Site
Osaka, Japan, 530-0012
Novartis Investigative Site
Osaka, Japan, 545-8586
Novartis Investigative Site
Saitama, Japan, 337-0012
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01119937     History of Changes
Other Study ID Numbers: CNVA237A1302
Study First Received: May 5, 2010
Results First Received: November 20, 2012
Last Updated: December 12, 2012
Health Authority: United States: Food and Drug Administration
Japan: Ministry of Health, Labor and Welfare

Keywords provided by Novartis:
COPD
NVA237

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Tiotropium
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014