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

NCT03184987 | Completed Phase 3 Results

• 1 other identifier: 207236
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 13

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.

Conditions

Asthma

Keywords

fluticasone furoate; fixed dose combination; Japanese subjects; vilanterol; asthma; umeclidinium bromide; closed triple therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

  An adverse event (AE) is any untoward medical occurrence in clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose: result in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect, other important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcome mentioned before. Intent-To-Treat (ITT) Population comprised of all participants who received at least one dose of study treatment in the treatment period.

  Up to Week 52

Secondary Outcomes (19)

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (Day 1), Weeks 4, 12, 24, 36 and 52

• Change From Baseline in Pulse Rate

  Baseline (Day 1), Weeks 4, 12, 24, 36 and 52

• Change From Baseline in PR Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)

  Baseline (Day 1), Weeks 4, 24 and 52

• Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

  Baseline (Day 1), Weeks 12, 24 and 52

• Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

  Baseline (Day 1), Weeks 12, 24 and 52

Study Arms (2)

FF/UMEC/VI 100/62.5/25 mcg closed triple therapy

EXPERIMENTAL

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; Drug: Salbutamol; Other: ACQ-7

FF/UMEC/VI 200/62.5/25 mcg closed triple therapy

EXPERIMENTAL

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; Drug: Salbutamol; Other: ACQ-7

Interventions

FF/UMEC/VI 100/62.5/25 mcg DRUG

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.

FF/UMEC/VI 100/62.5/25 mcg closed triple therapy

FF/UMEC/VI 200/62.5/25 mcg DRUG

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.

FF/UMEC/VI 200/62.5/25 mcg closed triple therapy

Salbutamol DRUG

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

FF/UMEC/VI 100/62.5/25 mcg closed triple therapy; FF/UMEC/VI 200/62.5/25 mcg closed triple therapy

ACQ-7 OTHER

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

FF/UMEC/VI 100/62.5/25 mcg closed triple therapy; FF/UMEC/VI 200/62.5/25 mcg closed triple therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead
• York Bioanalytical Solution: collaborator
• BI Medical.Inc.: collaborator
• SRL Medisearch Inc.: collaborator
• Parexel: collaborator
• Q2 Solutions: collaborator

Study Sites (13)

GSK Investigational Site

Gifu, 509-6134, Japan

Location

GSK Investigational Site

Gunma, 372-0831, Japan

Location

GSK Investigational Site

Gunma, 373-0807, Japan

Location

GSK Investigational Site

Hiroshima, 732-0052, Japan

Location

GSK Investigational Site

Kagawa, 762-8550, Japan

Location

GSK Investigational Site

Kanagawa, 236-0004, Japan

Location

GSK Investigational Site

Kyoto, 607-8062, Japan

Location

GSK Investigational Site

Okinawa, 901-2121, Japan

Location

GSK Investigational Site

Tokyo, 103-0027, Japan

Location

GSK Investigational Site

Tokyo, 134-0083, Japan

Location

GSK Investigational Site

Tokyo, 157-0066, Japan

Location

GSK Investigational Site

Tokyo, 169-0073, Japan

Location

GSK Investigational Site

Toyama, 937-0042, Japan

Location

MeSH Terms

Conditions

Asthma

Interventions

Albuterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 14, 2017
• Study Start: June 22, 2017
• Primary Completion: June 25, 2019
• Study Completion: June 25, 2019
• Last Updated: May 29, 2020
• Results First Posted: May 29, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

JP (13)