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

Chronic Obstructive Pulmonary Disease Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01119937
• Other study ID #: CNVA237A1302
• Status: Completed
• Phase: Phase 3
• First received: May 5, 2010
• Last updated: December 12, 2012
• Start date: May 2010

Study information

• Verified date: November 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationJapan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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) .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. primary completion date: November 2011
• 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 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

Study Design

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• NVA237
50µg capsules for inhalation, delivered via a single dose dry powder inhaler (Concept 1®)
• Tiotropium
18µg capsules for inhalation, delivered via HandiHaler®

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Asahikawa	Hokkaido
Japan	Novartis Investigative Site	Bunkyo-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Himeji-city	Hyogo
Japan	Novartis Investigative Site	Iizuka	Fukuoka
Japan	Novartis Investigative Site	Inashiki-gun	Ibaraki
Japan	Novartis Investigative Site	Kasaoka	Okayama
Japan	Novartis Investigative Site	Kawasaki	Kanagawa
Japan	Novartis Investigative Site	Kitakyushu	Fukuoka
Japan	Novartis Investigative Site	Kitakyushu	Fukuoka
Japan	Novartis Investigative Site	Kochi
Japan	Novartis Investigative Site	Kurume	Fukuoka
Japan	Novartis Investigative Site	Matsusaka-city	Mie
Japan	Novartis Investigative Site	Morioka	Iwate
Japan	Novartis Investigative Site	Nagaoka	Niigata
Japan	Novartis Investigative Site	Nagaoka-City	Niigata
Japan	Novartis Investigative Site	Naka-gun	Ibaraki
Japan	Novartis Investigative Site	Nakano-ku	Tokyo
Japan	Novartis Investigative Site	Obihiro	Hokkaido
Japan	Novartis Investigative Site	Ohta-ku	Tokyo
Japan	Novartis Investigative Site	Onojo	Fukuoka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osakasayama	Osaka
Japan	Novartis Investigative Site	Saitama
Japan	Novartis Investigative Site	Sakai	Osaka
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Sashima-gun	Ibaraki
Japan	Novartis Investigative Site	Sendai	Miyagi
Japan	Novartis Investigative Site	Shimotsuka-gun	Tochigi
Japan	Novartis Investigative Site	Takarazuka	Hyogo
Japan	Novartis Investigative Site	Takatsuki	Osaka
Japan	Novartis Investigative Site	Tsuyama	Okayama
Japan	Novartis Investigative Site	Ube	Yamaguchi
Japan	Novartis Investigative Site	Uji	Kyoto
Japan	Novartis Investigative Site	Yabu	Hyogo
Japan	Novartis Investigative Site	Yamagata city	Yamagata
Japan	Novartis Investigative Site	Yanagawa	Fukuoka
Japan	Novartis Investigative Site	Yokohama	Kanagawa
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, 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.	52 weeks	Yes
Secondary	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.	Weeks 12, 24, 36 and 52	No
Secondary	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.	Weeks 12, 24, 36 and 52	No
Secondary	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.	52 weeks	No
Secondary	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.	52 weeks	No
Secondary	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.	Weeks 12, 24, 36, 52	No
Secondary	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.	52 weeks	No
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 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	52 weeks	Yes
Secondary	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.	52 weeks	Yes
Secondary	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).	52 weeks	Yes