Clinical trial NCT01702363: Long-term Safety Study for GSK573719 in Japanese
Official title: A 52-week, Multi-centre, Open-label Study to Evaluate the Safety and Tolerability of GSK573719 125 mcg Once-daily Via Novel Dry Powder Inhaler (nDPI) in Japanese Subjects With Chronic Obstructive Pulmonary Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Chronic Obstructive Pulmonary Disease (COPD), GSK573719, Pharmacogenetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-10-08
Enrollment: 131
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the safety and tolerability of GSK573719 Inhalation Powder 125 mcg once-daily over 52 weeks in Japanese subjects with COPD.

Detailed description: Chronic Obstructive Pulmonary Disease (COPD) treatment guidelines recommend an incremental approach to pharmacological treatment as the disease state worsens, involving the use of combinations of drug classes with different or complementary mechanisms of action \[Celli, 2004, GOLD 2009\]. As disease progresses from mild to moderate, regular treatment with one or more long-acting bronchodilators is recommended. Inhaled bronchodilators, including beta2 agonists and anticholinergics are included with inhaled corticosteroids (ICS) therapy and are mainstays of therapy in patients diagnosed with COPD. Since GSK573719 Inhalation Powder is expected to be used for chronic management of COPD as long-acting muscarinic antagonist (LAMA), this study is intended to evaluate the safety and tolerability of long-term administration of GSK573719 Inhalation Powder 125 mcg in Japanese patients with COPD at doses possibly used to be in Japan.

In this study, patient safety will also be monitored by evaluating pulmonary function and clinical symptoms.

Eligibility criteria: Inclusion Criteria:

* Outpatient.
* A signed and dated written informed consent prior to study participation.
* Japanese subjects 40 years of age or older at Visit 1.
* Male or female subjects. A female is eligible if she is of: Non-child bearing potential or Child bearing potential agrees to one of the contraceptive methods.
* Subjects with a clinical history of COPD in accordance with the definition by COPD domestic guideline.
* Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years at Visit 1.
* Subject with a measured post-salbutamol forced expiratory volume/forced vital capacity (FEV1/FVC) ratio of \<70% and Subjects with a measured post-salbutamol FEV1 \<80% of predicted normal values.

Exclusion Criteria (Visit 1):

* Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* A current diagnosis of asthma.
* Known respiratory disorders other than COPD.
* Subjects with historical or current evidence of clinically significant abnormalities that are uncontrolled.
* A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD.
* Allergy or hypersensitivity to muscarinic, beta2-agonist, lactose/milk protein or magnesium stearate or a condition that contraindicates participation.
* Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
* Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).
* An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1.
* Significantly abnormal finding from clinical chemistry or hematology, tests at Visit 1.
* Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day.
* Regular use (prescribed every day, not for as-needed use) of short-acting bronchodilators (e.g., salbutamol) via nebulized therapy.
* Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1.
* A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
* Affiliation with Investigator Site.
* Previous use of GSK573719, the GSK573719/GW642444 combination.
* Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer).

Exclusion Criteria (Visit 2):

- COPD Exacerbation during run-in period: Subject must not have experienced a COPD exacerbation or a lower respiratory tract infection during run-in or at Visit 2.

Primary outcomes:
measure: Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) Throughout the Treatment Period
timeFrame: From the first dose of study medication up to 52 weeks
measure: Number of Participants With AEs Classified by the Indicated Maximum Grade Severity Throughout the Treatment Period
timeFrame: From the first dose of study medication up to 52 weeks
Secondary outcomes:
measure: Basophil, Eosinophil, Lymphocyte, Monocyte, and Total Neutrophil Values at Baseline (BL) (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit
measure: Eosinophil Values, Total Neutrophil Values, Platelet Count, and White Blood Cell (WBC) Count at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Hemoglobin, Albumin, and Total Protein Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Hematocrit Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, and Gamma Glutamyl Transferase (GGT) Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the WD Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24, Week36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the WD Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Calcium, Chloride, Glucose, Carbon Dioxide/Bicarbonate (CO2/HCO3), Potassium, Sodium, Inorganic Phosphorus, and Urea/Blood Urea Nitrogen (Urea/BUN) Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Change From BL in Blood Pressure Throughout the Treatment Period
timeFrame: BL(Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit
measure: Change From BL in Heart Rate Throughout the Treatment Period
timeFrame: BL (Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit
measure: Number of Participants With Abnormal Findings in 12-lead Electrocardiograms (ECG) at the Indicated Time Points
timeFrame: BL (Screening Visit: Week -2), Week 12, Week 24,Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Gunma
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ishikawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Oita
country: Japan
facility: GSK Investigational Site
city: Oita
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yamanashi
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Yamagata E, Soutome T, Hashimoto K, Mihara K, Tohda Y. Long-term (52 weeks) safety and tolerability of umeclidinium in Japanese patients with chronic obstructive pulmonary disease. Curr Med Res Opin. 2016 May;32(5):967-73. doi: 10.1185/03007995.2016.1140029. Epub 2016 Feb 18.