Efficacy and Safety Study of Fluticasone Proponate Inhalation Solution in Adult and Adolescent Asthma

NCT01687283 | Completed Phase 3 Results

• 1 other identifier: 114219
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 25

Brief Summary

This is a multicentre, randomized, single-blind, active-controlled, parallel-group phase III local registration study for a treatment period of 12 weeks. This study aims to assess the effectiveness and safety of fluticasone propionate 1mg via nebulizer BID in treatment of Chinese adult and adolescent patients with severe persistent asthma for a treatment period of 12 weeks versus budesonide 2mg via nebulizer BID. The steady-state plasma pharmacokinetics of fluticasone propionate inhalation solution will also be assessed.

Conditions

Asthma

Keywords

fluticasone propionate inhalation solution; budesonide suspension for inhalation; efficacy; severe persistent asthma; pharmacokinetics; safety

Outcome Measures

Primary Outcomes (2)

• Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population

  The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model. Abbreviations used in statistical analysis section: standard deviation (SD) and significance (sig)

  Baseline (Visit 2) and up to Week 12

• Change From Baseline (Day 1 of Trt Period/Visit 2) in AM PEF Over 12 Weeks in Per Protocol Population

  The peak expiratory flow (PEF) is a person's maximum speed of expiration, A peak flow meter was issued to participants at Visit 1 to measure the morning PEF prior to study drug and rescue medication. The best of three attempts was recorded by the participants in the diary cards. Baseline value was the assessment at Visit 2. The raw and change from baseline in daily AM PEF averaged over the 12-week treatment period The mean value was considered missing if less than 4 days were recorded in the baseline week prior to randomization or if less than 4 days are recorded after randomization. Analysis was performed using analysis of covariance (ANCOVA) model.

  Baseline (Visit 2) and up to Week 12

Secondary Outcomes (9)

• Mean Change of Evening PEF From Baseline Over 12 Weeks

  Baseline (Visit 2) and up to Week 12

• Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks

  Baseline (Visit 2) and over 12 Weeks

• Median Day-time and Night-time Symptom Scores Per Participant Over 12 Weeks

  Over 12 Weeks

• Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks

  Baseline and over 12 weeks

• Median Number of Times Rescue Medication Use Over 12 Weeks

  Up to week 12

Study Arms (2)

fluticasone propionate

EXPERIMENTAL

1 mg BID inhalation via nebulizer

Drug: fluticasone propionate inhalation solution

budesonide suspension

ACTIVE COMPARATOR

2 mg BID inhalation via nebulizer

Drug: budesonide suspension

Interventions

fluticasone propionate inhalation solution DRUG

1 mg BID inhalation for 12 weeks with one possible chance to change to 0.5 mg BID

fluticasone propionate

budesonide suspension DRUG

2 mg BID inhalation for 12 weeks with one possible chance to change to 1 mg BID

budesonide suspension

Eligibility Criteria

• Age: 17 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese male or female outpatients aged \>=17 years and \<=70 years
• A female is eligible to enter and participate in this study if she is:
• Non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is pre-menarchal, post-menopausal), or Child-bearing potential, has a negative urinary pregnancy test at screening and agrees to take contraceptive precautions (including abstinence) (referring to appendix 1: Highly Effective Methods For Avoidance Of Pregnancy In Women Of Childbearing Potential) which, in the opinion of the investigator are adequate to prevent pregnancy during the study.
• A documented clinical history of asthma for a period of at least 12 weeks prior to Visit 1 based on the Guidance of Asthma Management and Prevention 2008 in China (refer to appendix 2).
• Demonstrated \>=12% and \>=200mL reversibility of FEV1 within 15-30minutes following inhalation of 200-400ug of salbutamol aerosol within 12 months prior to visit 1 or at the Screening Visit.
• Subjects have pre-bronchodilator FEV1% predicted between \>=40% and \<80% at visit 1.
• Subjects on a stable dose at least 2 weeks with high dose ICS (eg. Fluticasone Propionate 500ug twice daily or other ICS with equivalence doses, refer to Appendix 3) or moderate dose ICS plus LABA (eg. Fluticasone Propionate/Salmoterol 250/50ug , twice daily; or Budesonide/Formoterol Fumarate in maintainance160/4.5ug, two inhalation, twice daily; or other product equivalence doses).
• Subjects and/or their legally acceptable representative (if applicable) is willing to give informed consent to participate in the study, and having ability to comply with study procedures (including patients can use Nebulizer correctly, be able to understand and complete the diary cards and be able to record their PEF using a peak flow meter). The subjects and/or their legally acceptable representative (if applicable) will need to give additional informed consent to be eligible for blood pharmacokinetic samplings.

You may not qualify if:

• History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
• Bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of visit 1 and 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.
• A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
• Subjects have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
• Subjects will not b eligible for the run-in if he/she has clinical visual evidence of candidias at visit 1.
• Current smoker or a smoking history of 10 pack years or more. A subject may not have used inhaled tobacco products (i.e., cigarettes, cigars or pipe tobacco) within the past 3 months.
• Patients who are pregnant or lactating.
• Patients having any known or suspected hypersensitivity to corticosteroids or the excipients of study drug, including Polysorbate 20, Sorbitan monolaurate, Monosodium phosphate dehydrate, Dibasic sodium phosphate anhydrous, Sodium Chloride and Water for Injection.
• Patients who have evidence of alcohol abuse.
• Patients who will have a pre-planned surgery operation in 6 months.
• Liver function tests: aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \>= 2 × upper limit of normal (ULN) or alkaline phosphatase (ALP) / bilirubin \>1.5 × ULN (isolated bilirubin \>1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Has QTc \>= 450 msec or \>= 480 msec for patients with bundle branch block at the time of screening.
• A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub Investigator, study coordinator, or employee of the participating Investigator.
• No subject is permitted to perform night shift work from Visit 1 until completion of the study treatment period.
• Use of the following medications within the following time intervals prior to visit 1 or during the study: Medication / No use within the following time intervals prior to Screening (Visit 1) or at any time during the study Systemic or oral corticosteroids / 2 weeks Depot corticosteroids /12 weeks Anti-IgE (e.g. Xolair)/ 12 weeks Oral long-acting beta2-agonists (e.g. bambuterol) and inhaled long-acting beta2-agonists (e.g. salmeterol, formoterol) or combination products containing inhaled long-acting beta2-agonists (e.g. Seretide, Symbicort) / 12 hours (the stable dose of ICS/LABA combination within 2 weeks prior to Visit 1 could be continued during the run-in period) Theophyllines, slow-release bronchodilators, anticholinergics, ketotifen, nedocromil sodium, sodium cromoglycate, Anti-leukotrienes including suppressors of leukotriene production and antagonists / 1 day Inhaled short-acting beta2-agonist / 4 hours (salbutamol will be supplied for rescue during the study) Potent Cytochrome P450 3A4 inhibitors(e.g. ritonavir, ketoconazole, itraconzole) / 4 weeks Prescription or over the counter medication that would significantly affect the course of asthma, or interact with sympathomimetic amines, such as: anticonvulsants (barbiturates, hydantoins, carbamazepine); polycyclic antidepressants; beta-adrenergic blocking agents; phenothiazines and monoamine oxidase (MAO) inhibitors /1 day Chinese traditional medicines used for treatment of asthma and other allergic diseases / 1 week Any other investigational drug / 30 days or within 5 half lives, whichever is longer

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (25)

GSK Investigational Site

Guangzhou, Guangdong, 510080, China

Location

GSK Investigational Site

Guangzhou, Guangdong, 510180, China

Location

GSK Investigational Site

Zhanjiang, Guangdong, 524001, China

Location

GSK Investigational Site

Changsha, Hunan, 410004, China

Location

GSK Investigational Site

Changsha, Hunan, 410011, China

Location

GSK Investigational Site

Xuzhou, Jiangsu, 221006, China

Location

GSK Investigational Site

Nanchang, Jiangxi, 330006, China

Location

GSK Investigational Site

Shenyang, Liaoning, 110001, China

Location

GSK Investigational Site

Shenyang, Liaoning, 110015, China

Location

GSK Investigational Site

Yinchuan, Ningxia, 750004, China

Location

GSK Investigational Site

Jinan, Shandong, 250012, China

Location

GSK Investigational Site

Jinan, Shandong, 250013, China

Location

GSK Investigational Site

Qingdao, Shandong, 266071, China

Location

GSK Investigational Site

Taiyuan, Shanxi, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610041, China

Location

GSK Investigational Site

Chengdu, Sichuan, 610072, China

Location

GSK Investigational Site

Hangzhou, Zhejiang, China

Location

GSK Investigational Site

Beijing, 100029, China

Location

GSK Investigational Site

Beijing, 100088, China

Location

GSK Investigational Site

Chongqing, 400038, China

Location

GSK Investigational Site

Chongqing, China

Location

GSK Investigational Site

Hangzhou, 310016, China

Location

GSK Investigational Site

Shanghai, 200025, China

Location

GSK Investigational Site

Shanghai, 200072, China

Location

GSK Investigational Site

Wuxi, 214023, China

Location

Related Links

• IPD for this study will be made available via the Clinical Study Data Request site.

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

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: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2012
• First Posted: September 18, 2012
• Study Start: September 27, 2012
• Primary Completion: November 7, 2013
• Study Completion: November 7, 2013
• Last Updated: October 11, 2018
• Results First Posted: June 20, 2017

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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

CN (25)