A Long-term Safety Study of Fluticasone Furoate (FF)/GW642444 and FF in Japanese Subjects With Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01244984
First received: November 18, 2010
Last updated: August 15, 2013
Last verified: June 2013
  Purpose

The primary purpose of the study is to assess the safety and tolerability of 52-week teatment with fluticasone furoate/GW642444 inhalation powder once-daily and FF inhalation powder once-daily in Japanese adult subjects with asthma.


Condition Intervention Phase
Asthma
Drug: Fluticasone Furoate/GW642444 Inhalation Powder
Drug: Fluticasone Furoate Inhalation Powder
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Long-term Study to Evaluate the Safety and Tolerability of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and FF Inhalation Powder in Japanese Subjects With Asthma

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious Adverse Event (SAE) [ Time Frame: From the start of investigational product to the last dose of treatment (up to Week 52/Withdrawal [WD]) ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs (occurring at a frequency threshold >=5%) and SAE.


Secondary Outcome Measures:
  • Laboratory Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameters of Eosinophils, Platelet Count, White Blood Cell (WBC), and Total Neutrophils at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Hemoglobin at Baseline (Week -2), Week 12,Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Hematocrit at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Red Blood Cell Count at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Albumin and Total Protein (TP) at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LDH) at BL (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (BL) (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Bilirubin (Direct [BD], Indirect [BI], Total [BT], Creatinine, and Uric Acid at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Urine Potential of Hydrogen (pH) at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Urine samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Laboratory Parameter of Urine Specific Gravity (USG) at Baseline (Week -2), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Urine samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

  • Number of Participants for the Indicated Uninalysis Parameters Tested by Dipstick at Baseline (BL), Week 12, Week 24, and Week 52/WD [ Time Frame: Baseline (Week -2), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Urinalysis parameters included: Urine Occult Blood (UOB), Urine Glucose (UG), Urine Ketones (UK), Urine Protein (UP), and Urine Leukocyte Esterase test for detecting White Blood Cell (UWBC). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results can be read as negative (Neg), Trace (TRA), 1+, 2+, and 3+, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had neg, trace, 1+, 2+, and 3+ levels at Baseline (Week -2) and Week 52/WD.

  • Change From Baseline in the 24-hour Urinary Cortisol Excretion [ Time Frame: Baseline (Week 0), Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Urine samples were collected for measurement of urinary cortisol excretion at the following scheduled time points: Baseline (Week 0), Week 24, and Week 52/WD. The 24-hour urinary cortisol excretion was calculated by multiplying the total volume of urine by the concentration of urinary cortisol. Cortisol is a hormone released from the adrenal gland that helps in fat, protein, and carbohydrate metabolism. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

  • Change From Baseline in Blood Pressure [ Time Frame: Baseline (Week 0), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline (Week 0), Weeks 12, 24 and Week 52/WD. Blood pressure was measured in a sitting position after a participant was kept at rest for at least 5 minutes. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  • Change From Baseline in Heart Rate (HR) [ Time Frame: Baseline (Week 0), Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    Heart rate was measured in a sitting position after a participant was kept at rest for at least 5 minutes at Baseline (Week 0), Weeks 12, 24 and Week 52/WD. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  • Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings [ Time Frame: Week 12, Week 24, and Week 52/WD ] [ Designated as safety issue: No ]
    A 12-lead ECG was recorded in a supine position after the participant was kept at rest in this position for at least 5 minutes at assessment time points (Baseline[Week -2], Week 12, 24 and Week 52/WD) in the treatment period. Data are presented for clinically significant (CS) as well as not clinically significant (NCS) abnormal (Abn) findings. Any abnormal ECG, including those that worsen from Baseline, and determined clinically significant by the assessment of the investigator were recorded as CS.

  • Number of Participants With Severe Asthma Exacerbation During the Study Treatment [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    A severe asthma exacerbation is defined as the deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Courses of corticosteroids separated by 1 week or more were treated as separate severe exacerbations.

  • Change From Baseline in Diary Data - Morning (AM) Peak Expiratory Flow (PEF) and Evening (PM) PEF During the Study Treatment [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    Change from Baseline in AM and PM PEF at 52 weeks of evaluation period during study treatment was recorded in the dairy record card. The Baseline value was calculated as the mean of all available data recorded during the7 days immediately prior to the treatment start date (including Day 1: Day 1 is treatment start date). The PEF is defined as the greatest rate of airflow that can be achieved during forced exhalation beginning with the lungs fully inflated.

  • Change From Baseline in Asthma Symptom Score During the Study Treatment [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    The Baseline value was calculated as the mean of all available data recorded during the 7 days immediately prior to Visit 2 (treatment assignment visit). Participants entered their asthma symptom score in the patient diary twice daily (morning and evening). Daytime asthma symptom scores: 0-no asthma symptoms, 1-one episode of short-time asthma symptoms, 2-two or more episodes of short-time asthma symptoms, 3-asthma symptoms occurring during most part of daytime without interference with daily life activities, 4-asthma symptoms occurring during most part of daytime with interference with daily life activities, 5-severe asthma symptoms that disable working or daily life activities. Nighttime asthma symptom scores: 0-no asthma symptoms, 1-one awakening due to asthma symptoms, 2-two or more awakenings due to asthma symptoms, 3-asthma symptoms almost prevented the participant from sleeping, 4-severe asthma symptoms completely prevented from sleeping.

  • Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the Study Treatment [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    Participants who were symptom free for 24-hours were assessed. Change from Baseline is calculated as the value at Week 52 minus the value at Baseline.

  • Change From Baseline in the Percentage of Rescue-free 24-hour Periods [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    The time span during which the participants did not have to take any rescue medication (medication intended to relieve symptoms immediately) was considered as a rescue free period. Change from Baseline is calculated as the value at Week 52 minus the value at Baseline.

  • Number of Rescue Medication Inhalations [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: No ]
    Salbutamol inhaler was used as the rescue medication. Participants entered the number of rescue medication inhalations in the patient diary twice daily (morning and evening).


Enrollment: 243
Study Start Date: July 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluticasone Furoate/GW642444
Combination inhaled corticosteroid and long-acting beta2-agonist
Drug: Fluticasone Furoate/GW642444 Inhalation Powder
Fluticasone Furoate/GW642444 inhalation powder inhaled orally once daily for 52 weeks
Experimental: Fluticasone Furoate
Inhaled corticosteroid
Drug: Fluticasone Furoate Inhalation Powder
Fluticasone Furoate inhalation powder inhaled orally once daily for 52 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Out patient at least 18 years of age
  • Both genderds; females of childbearing potential must be willing to use birth control method
  • A diagnosis of asthma at least 6 months prior to Screening
  • A best FEV1 of at least 50% of the predicted nomal value at Screening
  • Subjects have been receiving maintanance therapy for asthma, for at least 4 weeks prior to Screening

Exclusion Criteria:

  • History of life-threating asthma
  • Respiratory infection or oral candidiasis
  • Asthma exacerbation within 12 weeks
  • Concurrent respiratory disease or other disease that would confound study participation or affect subject safety
  • Allergies to study drugs, study drugs7 excipients, medications related to study drugs
  • Taking another investigational medication or medication prohibited for use during this study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01244984

Locations
Japan
GSK Investigational Site
Chiba, Japan, 277-0863
GSK Investigational Site
Fukuoka, Japan, 816-0813
GSK Investigational Site
Fukuoka, Japan, 802-0083
GSK Investigational Site
Gifu, Japan, 501-6062
GSK Investigational Site
Gunma, Japan, 373-0021
GSK Investigational Site
Hiroshima, Japan, 739-0402
GSK Investigational Site
Hiroshima, Japan, 732-0062
GSK Investigational Site
Hiroshima, Japan, 730-0844
GSK Investigational Site
Hyogo, Japan, 670-0046
GSK Investigational Site
Hyogo, Japan, 672-8064
GSK Investigational Site
Hyogo, Japan, 665-0827
GSK Investigational Site
Ibaraki, Japan, 302-0022
GSK Investigational Site
Kanagawa, Japan, 231-8682
GSK Investigational Site
Kanagawa, Japan, 253-0041
GSK Investigational Site
Kyoto, Japan, 601-1495
GSK Investigational Site
Kyoto, Japan, 615-8087
GSK Investigational Site
Miyagi, Japan, 983-8520
GSK Investigational Site
Miyagi, Japan, 983-0824
GSK Investigational Site
Nagano, Japan, 390-8510
GSK Investigational Site
Nagano, Japan, 390-0303
GSK Investigational Site
Okayama, Japan, 701-0304
GSK Investigational Site
Okayama, Japan, 700-0862
GSK Investigational Site
Okayama, Japan, 714-0081
GSK Investigational Site
Osaka, Japan, 569-1192
GSK Investigational Site
Osaka, Japan, 589-0022
GSK Investigational Site
Osaka, Japan, 545-8586
GSK Investigational Site
Tokyo, Japan, 185-0014
GSK Investigational Site
Tokyo, Japan, 134-0083
GSK Investigational Site
Tokyo, Japan, 105-0004
GSK Investigational Site
Toyama, Japan, 937-0066
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01244984     History of Changes
Other Study ID Numbers: 113989
Study First Received: November 18, 2010
Results First Received: June 6, 2013
Last Updated: August 15, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
asthma
Fluticasone furoate
GW642444

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Fluticasone
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 15, 2014