A Long-term Safety Study of Fixed Dose Combination Therapy Fluticasone Furoate/Umeclidinium Bromide/Vilanterol Trifenatate in Japanese Subjects With Asthma

ID: NCT03184987
Status: Recruiting
Phase: Phase 3
Start Date: June 22, 2017
First Submitted: June 09, 2017
Last Updated: February 22, 2018
Results: N/A
Organization: GlaxoSmithKline
Sponsors & Collaborators: GlaxoSmithKline, York Bioanalytical Solution, BI Medical.Inc, SRL Mediserch.Inc, Parexel International Japan, Q2 Solutions
Location: Japan
Conditions: Asthma
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Study Description

Brief Summary

Despite availability of treatments and published guidelines, subjects may have asthma that is inadequately controlled. GlaxoSmithKline is currently developing a once-daily 'closed' triple therapy of an Inhaled Corticosteroids/Long-Acting Beta-2-Agonists/Long-Acting Muscarinic Antagonist (ICS/LAMA/LABA) combination (Fluticasone Furoate/Umeclidinium Bromide/Vilanterol Trifenatate [FF/UMEC/VI]) in a single device, with the aim of providing a new treatment option for the management of asthma by improving lung function, health-related quality of life (HRQoL) and symptom control over established combination therapies. This study has 3 study periods: Run-in, Treatment period and a Follow-up period. Eligible subjects who meet the pre-defined criteria at screening (Visit 1) will enter into a 2-week run-in period. Subjects will continue their pre-screening inhaled medications for asthma (ICS+LABA or ICS+LABA+LAMA) without any change in regimen/dosage until day before Visit 2. At Visit 2 subjects will be allocated to either FF/UMEC/VI 100/62.5/25 or FF/UMEC/VI 200/62.5/25 micrograms (mcg) treatment depending on the asthma control status for 52 weeks. Switching medication from FF/UMEC/VI 100/62.5/25 to FF/UMEC/VI 200/62.5/25 will be permitted in accordance with the control status of the subject assessed by Asthma Control Questionnaire (ACQ)-7 at Week 24 of the treatment period. A follow-up visit will be conducted for approximately 1 week. Subjects will be provided with salbutamol as a rescue medication throughout the study.

Detailed Description

Condition or disease Intervention/treatment Phase

Asthma
Drug: FF/UMEC/VI 100/62.5/25 mcg
Other Names
Drug: FF/UMEC/VI 200/62.5/25 mcg
Other Names
Drug: Salbutamol
Other Names
Other: ACQ-7
Other Names
Phase 3

Tracking Information

First Submitted DateJune 09, 2017
Last Update Posted DateFebruary 22, 2018
Actual Start DateJune 22, 2017
Anticipated Completion DateAugust 01, 2019
Actual Primary Completion DateAugust 01, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Number of subjects with any Adverse Events (AEs) and any serious adverse events (SAEs) [Time Frame: Up to 374 days]

    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Systolic and diastolic blood pressure assessment as a measure of safety [Time Frame: Up to Week 52]

    Blood pressure will be measured in a sitting position after 5 minutes of rest.

  • Pulse rate assessment as a measure of safety [Time Frame: Up to Week 52]

    Pulse rate will be measured in a sitting position after 5 minutes of rest.

  • Electrocardiogram (ECG) measurements as a measure of safety [Time Frame: Up to Week 52]

    Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.

  • Number of subjects with abnormal clinical chemistry parameters [Time Frame: Up to Week 52]

    Blood samples will be collected to analyze platelet count, hemoglobin, hematocrit, white blood cells (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cells (RBC) indices including mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH).

  • Number of subjects with abnormal hematological parameters [Time Frame: Up to Week 52]

    Blood samples will be collected to analyze blood urea nitrogen(BUN), creatinine, glucose, potassium, sodium, calcium, aspartate amino-transferase (AST) (Serum glutamic-oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (Serum glutamic-pyruvic transaminase [SGPT]), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, total protein, and albumin.

  • Number of subjects with abnormal urinalysis [Time Frame: Up to Week 52]

    Urine samples will be collected to analyze potential of hydrogen (pH), glucose, protein, blood, ketones by dipstick, specific gravity and microscopic examination (if blood or protein is abnormal)

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Long-term Safety Study of Fixed Dose Combination Therapy Fluticasone Furoate/Umeclidinium Bromide/Vilanterol Trifenatate in Japanese Subjects With Asthma
Official TitleA Phase III, 52-week, Open-label Study to Evaluate Long-term Safety of Fixed Dose Combination Therapy Fluticasone Furoate/Umeclidinium Bromide/Vilanterol Trifenatate in Japanese Patients With Asthma
Brief Summary

Despite availability of treatments and published guidelines, subjects may have asthma that is inadequately controlled. GlaxoSmithKline is currently developing a once-daily 'closed' triple therapy of an Inhaled Corticosteroids/Long-Acting Beta-2-Agonists/Long-Acting Muscarinic Antagonist (ICS/LAMA/LABA) combination (Fluticasone Furoate/Umeclidinium Bromide/Vilanterol Trifenatate [FF/UMEC/VI]) in a single device, with the aim of providing a new treatment option for the management of asthma by improving lung function, health-related quality of life (HRQoL) and symptom control over established combination therapies. This study has 3 study periods: Run-in, Treatment period and a Follow-up period. Eligible subjects who meet the pre-defined criteria at screening (Visit 1) will enter into a 2-week run-in period. Subjects will continue their pre-screening inhaled medications for asthma (ICS+LABA or ICS+LABA+LAMA) without any change in regimen/dosage until day before Visit 2. At Visit 2 subjects will be allocated to either FF/UMEC/VI 100/62.5/25 or FF/UMEC/VI 200/62.5/25 micrograms (mcg) treatment depending on the asthma control status for 52 weeks. Switching medication from FF/UMEC/VI 100/62.5/25 to FF/UMEC/VI 200/62.5/25 will be permitted in accordance with the control status of the subject assessed by Asthma Control Questionnaire (ACQ)-7 at Week 24 of the treatment period. A follow-up visit will be conducted for approximately 1 week. Subjects will be provided with salbutamol as a rescue medication throughout the study.

Detailed Description

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
110
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Asthma
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: FF/UMEC/VI 100/62.5/25 mcg

Subjects will self-administer the study treatment via the ELLIPTA device. The ELLIPTA holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 100 mcg in each blister and the second strip contains UMEC 62.5 mcg and VI 25 mcg in each blister. ELLIPTA is a registered trademark of GSK groups of companies.

Other Names
Drug: FF/UMEC/VI 200/62.5/25 mcg

Subjects will self-administer the study treatment via the ELLIPTA device. The ELLIPTA holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 200 mcg in each blister and the second strip contains UMEC 62.5 mcg and VI 25 mcg in each blister. ELLIPTA is a registered trademark of GSK groups of companies.

Other Names
Drug: Salbutamol

Salbutamol is a rescue medication administered via metered-dose inhaler (MDI) which will be used when needed during the study.

Other Names
Other: ACQ-7

ACQ-7 will be used for the assessment of control status of asthma.

Other Names
Study Groups/Cohorts
FF/UMEC/VI 100/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.

FF/UMEC/VI 200/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.

Study Arms
Experimental FF/UMEC/VI 100/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
Drug : FF/UMEC/VI 100/62.5/25 mcg
Subjects will self-administer the study treatment via the ELLIPTA device. The ELLIPTA holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 100 mcg in each blister and the second strip contains UMEC 62.5 mcg and VI 25 mcg in each blister. ELLIPTA is a registered trademark of GSK groups of companies.

Experimental FF/UMEC/VI 100/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
Drug : Salbutamol
Salbutamol is a rescue medication administered via metered-dose inhaler (MDI) which will be used when needed during the study.

Experimental FF/UMEC/VI 100/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
Other : ACQ-7
ACQ-7 will be used for the assessment of control status of asthma.

Experimental FF/UMEC/VI 200/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
Other : ACQ-7
ACQ-7 will be used for the assessment of control status of asthma.

Experimental FF/UMEC/VI 200/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
Drug : FF/UMEC/VI 200/62.5/25 mcg
Subjects will self-administer the study treatment via the ELLIPTA device. The ELLIPTA holds 2 individual blister strips with 30 blisters on each strip: the first strip contains FF 200 mcg in each blister and the second strip contains UMEC 62.5 mcg and VI 25 mcg in each blister. ELLIPTA is a registered trademark of GSK groups of companies.

Experimental FF/UMEC/VI 200/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
Drug : Salbutamol
Salbutamol is a rescue medication administered via metered-dose inhaler (MDI) which will be used when needed during the study.

Arm Intervention/Treatment
Experimental FF/UMEC/VI 100/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
 Drug : FF/UMEC/VI 100/62.5/25 mcg
Experimental FF/UMEC/VI 100/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
 Drug : Salbutamol
Experimental FF/UMEC/VI 100/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
 Other : ACQ-7
Experimental FF/UMEC/VI 200/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
 Other : ACQ-7
Experimental FF/UMEC/VI 200/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
 Drug : FF/UMEC/VI 200/62.5/25 mcg
Experimental FF/UMEC/VI 200/62.5/25 mcg closed triple therapy
Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
 Drug : Salbutamol

Recruitment Information

Recruitment Status:Recruiting
Enrollment110
Completion DateAugust 01, 2019
Eligibility Criteria: Inclusion Criteria at the time of informed consent (Visit 0) and at screening (Visit 1).
- Age: Participant must be 18 years of age or older at the time of signing the informed consent.
- Ethnicity: Japanese
- Diagnosis: Subjects with a diagnosis of asthma as defined by the National Institutes of Health at least one year prior to providing informed consent.
- Current Asthma Maintenance Therapy: Outpatients are eligible if they have received ICS+LABA or ICS+LABA＋LAMA with asthma control status as Not well controlled with ICS (mid-dose) +LABA ; Not well controlled with ICS (high-dose) +LABA or Controlled with ICS (mid-dose) +LABA + LAMA; Not well controlled with ICS (mid-dose) +LABA + LAMA; Controlled with ICS (high-dose) +LABA + LAMA respectively in stable regimen and dosage for at least 4 weeks prior to screening visit (Visit 1) (with medium to high dose of ICS defined by the Japanese Guidelines [JGL]). Asthma Control Questionnaire (ACQ-6) will be used for the assessment of control status of asthma at Visit 1 (screening Visit) (i.e., less than or equal to 0.75 points shows controlled and > 0.75 shows not well controlled).
- Short-Acting Beta Agonists (SABAs): All subjects must be able to replace their current SABA inhaler with salbutamol aerosol inhaler at Visit 1 as needed for the duration of the study. Subjects should be able to withhold salbutamol for at least 6 hours prior to clinic visit.
- Sex: Male and/or female: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance from the screening visit until after the last dose of study medication and completion of the follow-up visit.
- Informed Consent: capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).

Exclusion Criteria at the time of informed consent (Visit 0) and at screening (Visit 1).
- Pneumonia: Chest X-ray documented pneumonia in the 6 weeks prior to Visit 1.
- Asthma Exacerbation: Any asthma exacerbation requiring a change in maintenance asthma therapy in the 6 weeks prior to Visit 1.
- COPD: Subjects with the diagnosis of chronic obstructive pulmonary disease, as per Global Initiative for Chronic Obstructive Lung Disease (GOLD 2016) guidelines, including history of exposure to risk factors (i.e., especially tobacco smoke, occupational dusts and chemicals, smoke from home cooking and heating fuels) (for tobacco smoke); post- salbutamol Forced Expiratory Volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of <0.70 and a post- salbutamol FEV1 of less than or equal to 70% of predicted normal values (diagnosis prior to Visit 1 acceptable);Onset of disease greater than or equal to 40 years of age.
- Concurrent respiratory disorders: Subjects with current evidence of pneumonia, active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases or abnormalities other than asthma.
- Risk Factors for Pneumonia: Immune suppression (e.g., HIV, lupus) or other risk factors for pneumonia (e.g., neurological disorders affecting control of the upper airway, such as Parkinson's disease, myasthenia gravis). Patients at potentially high risk (e.g., very low body mass index (BMI), severely malnourished, or very low FEV1) will only be included at the discretion of the Investigator.
- Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
- Unstable liver disease as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).Note: Chronic stable hepatitis B and C are acceptable if the subject otherwise meets entry criteria.
- Clinically significant ECG abnormality: Evidence of a clinically significant abnormality in the 12-lead ECG performed during screening. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. An abnormal and clinically significant finding is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following:
- Atrial fibrillation (AF) with rapid ventricular rate >120 beats per minute (bpm)
- Sustained or nonsustained ventricular tachycardia (VT)
- Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted)
- QT interval corrected for heart rate by Fridericia's formula (QTcF) greater than or equal to 500 milliseconds (msec) in patients with QRS <120 msec and QTcF greater than or equal to 530 msec in patients with QRS greater than or equal to 120 msec.
- Unstable or life threatening cardiac disease: subjects with any of the following at screening (Visit 1) would be excluded:
- Myocardial infarction or unstable angina in the last 6 months
- Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months
- New York Heart Association (NYHA) Class IV heart failure
- Antimuscarinic effects: Subjects with a medical condition such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy or bladder neck obstruction should only be included if in the opinion of the Investigator the benefit outweighs the risk and that the condition would not contraindicate study participation.
- Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the subject has been considered cured by treatment.
- Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
- Medication prior to spirometry: Subjects who are medically unable to withhold their salbutamol for the 6-hour period required prior to spirometry testing at each study visit.
- Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
- Allergy or hypersensitivity: A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta-agonist, lactose/severe milk protein or magnesium stearate.
- Tobacco use: Subjects who are: Current smokers (defined as subjects who have used inhaled tobacco products within the 12 months prior to Visit 1 [i.e., cigarettes, e-cigarettes/vaping, cigars or pipe tobacco]); Former smokers with a smoking history of greater than equal to 10 pack years (e.g., greater than equal to 20 cigarettes/day for 10 years).
- Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
- Affiliation with Investigator site: Study Investigators, sub-Investigators, study coordinators, employees of a participating Investigator or study site, or immediate family members of the aforementioned that is involved with this study.
- Inability to read: In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete study related materials.
Inclusion Criteria end of the run-in period (Visit 2)
- Asthma maintenance therapy: No changes in asthma maintenance therapy (excluding salbutamol inhalation aerosol provided at Visit 1) and control status during the run-in period. Asthma Control Questionnaire (ACQ-6 at screening and ACQ-7 at the end of the run-in period) will be used for the assessment of control status of asthma, i.e., 0.75 points shows controlled and >0.75 shows not well controlled.
- Concurrent conditions/medical history: Liver function test at Visit1
- ALT <2 x upper limit of normal (ULN)
- ALP less than or equal to 1.5 x ULN
- Bilirubin less than or equal to 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

Exclusion Criteria end of the run-in period (Visit 2)
- Respiratory Infection: Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
- Severe asthma exacerbation: Evidence of a severe exacerbation during screening or the run-in period, defined as 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.
- Laboratory test abnormalities: Evidence of clinically significant abnormal laboratory tests during screening or the run-in period which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality.
- There is no restriction on diet in this study.
- Use of tobacco products will not be allowed from screening until after the final follow-up visit. Caffeine and alcohol is allowed ad libitum.
- There is no restriction on activity in this study.
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Japan

Administrative Information

NCT Number:NCT03184987
Other Study ID Numbers
207236
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
GlaxoSmithKline
Collaborators
York Bioanalytical Solution
BI Medical.Inc
SRL Mediserch.Inc
Parexel International Japan
Q2 Solutions
Investigators
Study Director
GSK Clinical Trials
GlaxoSmithKline