A Study to Compare the Efficacy of Fluticasone Furoate/Vilanterol Inhalation Powder With Usual Inhaled Corticosteroids (ICS)/Long Acting Beta Agonists (LABA) in Persistent Asthma

NCT02446418 | Completed Phase 3 Results

• 1 other identifier: 116492
• Study Type: interventional
• Target: 423
• Locations: 2 countries
• Sites: 93

Brief Summary

The combination of FF, an ICS and VI, an orally inhaled LABA has been developed as a once-daily combination therapy for the long-term maintenance treatment of asthma in adults and children \>=12 years of age. Pivotal phase III studies have demonstrated the safety and efficacy of FF/VI in asthma. However, it is increasingly acknowledged that randomised clinical trials tend to be highly controlled and enrol a more highly selected subject population than is expected to be prescribed the medication post-approval. There is a need for data in a more representative population in close to a 'real life' conditions, where physicians have the ability to choose the best treatment in their view for any individual subject and adapt treatments to subjects' characteristics and response. This multi-center, open-label, randomized, parallel group study will evaluate the efficacy and safety of FF/VI compared with two usual ICS/LABA fixed combination (fluticasone propionate/salmeterol \[FP/S\] or budesonide/formoterol \[BUD/F\]) in subjects with persistent asthma, in a "close to real life" settings. FF/VI will be administered once-daily (QD) via ELLIPTA dry powder inhaler (DPI) and FP/S or BUD/F will be administered twice daily (BID) via DISKUS™ and TURBUHALER™ DPI respectively. ELLIPTA is a new powder inhaler designed to be easy to use. The total duration of subject participation will be approximately 6 months (24 weeks). ELLIPTA and DISKUS are registered trademarks of the GSK group of companies. TURBUHALER is a registered trademark of AstraZeneca.

Conditions

Asthma

Keywords

dry powder inahler; vilanerol; efficacy; safety; fluticasone furoate; quality of life

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Asthma Control Test (ACT) Total Score at Week 12

  The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control during the past 4 weeks on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented.

  Baseline and Week 12

Secondary Outcomes (2)

• Change From Baseline in ACT Total Score at Week 24

  Baseline and Week 24

• Percentage of Participants With Correct Use of Device, Defined as Not Making Any Critical or Non-critical Errors, at Week 12, and at Week 24 Independently of the Use at Week 12

  Week 12 and Week 24

Study Arms (2)

Fluticasone Furoate/Vilanterol

EXPERIMENTAL

Subjects will receive FF/VI 92 micrograms (mcg)/22 mcg or FF/VI 184 mcg/22 mcg as decided by the investigator QD via ELLIPTA DPI for 24 weeks.

Drug: Fluticasone Furoate; Drug: Vilanterol

FP/S OR BUD/F

ACTIVE COMPARATOR

Subjects will receive FP/S (250 mcg/50 mcg or 500 mcg/50mcg) twice daily via DISKUS or BUD /F (200 mcg/6mcg or 400 mcg/12mcg one or two inhalations) twice daily via TURBUHALER DPI as decided by the investigator for 24 weeks.

Drug: Fluticasone propionate; Drug: Salmeterol; Drug: Budesonide; Drug: Formoterol Fumarate

Interventions

Fluticasone Furoate DRUG

FF 92 mcg or 184 mcg blended with lactose administered once daily via ELLIPTA DPI

Fluticasone Furoate/Vilanterol

Vilanterol DRUG

Vilanterol 22 mcg blended with lactose and magnesium stearate administered once daily via ELLIPTA DPI

Fluticasone Furoate/Vilanterol

Fluticasone propionate DRUG

FP 250 mcg or 500 mcg blended with lactose administered twice daily via DISKUS DPI

FP/S OR BUD/F

Salmeterol DRUG

Salmeterol 50 mcg blended with lactose administered twice daily via DISKUS DPI

FP/S OR BUD/F

Budesonide DRUG

Budesonide 200 mcg or 400 mcg blended with lactose administered twice daily via TURBUHALER DPI

FP/S OR BUD/F

Formoterol Fumarate DRUG

Formoterol Furoate 6 mcg or 12 mcg blended with lactose administered twice daily via TURBUHALER DPI

FP/S OR BUD/F

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
• Gender and Age: Male or female subjects aged \>=18 and \<=75years of age at Screening visit.
• Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as: Pre-menopausal females with one of the following - Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause \[refer to laboratory reference ranges for confirmatory levels\]); Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
• Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until Week 24.
• GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP:
• This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant that meets the Standard Operating Procedure (SOP) effectiveness criteria including a \<1percent rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a \<1 percent rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject; Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
• Current Asthma Therapy: All subjects must be prescribed maintenance therapy and receiving ICS alone without LABA for at least 4 weeks prior to Randomisation visit; Other background asthma medication such as anti-leukotrienes or theophylline is permitted as an alternative to ICS alone, if initiated at least 4 weeks prior to screening visit.
• Subject questionnaires Subjects must be able to complete the questionnaires themselves.

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 within the last 6 months before Screening and Randomisation visit.
• Subjects having a severe and unstable asthma, with ACT score \< 15 at Visit 1 and at Visit 2, and/or a history of repeated severe exacerbations (3/year) and/or a severe exacerbation in the previous 6 weeks before Visit 1 and Visit 2.
• Chronic obstructive pulmonary disease (COPD) Respiratory Disease: A subject must not have current evidence or diagnosis of chronic obstructive pulmonary disease at Screening visit.
• Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years at screening \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\].
• Other diseases/abnormalities: Subjects with historical or current evidence of uncontrolled or clinically significant disease at Screening and Randomisation visit. 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.
• Subjects with a history of adverse reaction including immediate or delayed hypersensitivity to any intranasal, inhaled, or systemic corticosteroid and LABA therapy and to components of the inhalation powder (e.g., lactose, magnesium stearate) at Screening and Randomisation visit. In addition, subjects with a history of severe milk protein allergy that, in the opinion of the Investigator, contraindicates the subject's participation will also be excluded.
• Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Randomisation visit or within five half-lives (t½) of the prior investigational study (whichever is longer of the two), (if unsure discuss with the medical monitor prior to screening).
• Chronic user of systemic corticosteroids: A subject who, in the opinion of the Investigator, is considered to be a chronic user of systemic corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening) at Screening visit.
• Subjects treated by the monoclonal antibody omalizumab or mepolizumab at Visit 1. Treatment with omalizumab or mepolizumab is not allowed during the study.
• Subjects involved in other clinical trials at Screening visit.
• Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
• Subjects who plan to move away from the geographical area where the study is being conducted during the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (93)

GSK Investigational Site

Amiens, 80090, France

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GSK Investigational Site

Angers, 49000, France

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GSK Investigational Site

Avelin, 59710, France

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GSK Investigational Site

Bassussarry, 64200, France

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GSK Investigational Site

Beauzelle, 31700, France

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GSK Investigational Site

Bersée, 59235, France

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GSK Investigational Site

Bécon-les-Granits, 49370, France

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GSK Investigational Site

Béziers, 34500, France

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GSK Investigational Site

Biarritz, 64200, France

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GSK Investigational Site

Bourg-des-Comptes, 35890, France

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GSK Investigational Site

Broglie, 27270, France

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GSK Investigational Site

Bruay-la-Buissière, 62700, France

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GSK Investigational Site

Caen, 14000, France

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GSK Investigational Site

Cannes, 06614, France

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GSK Investigational Site

Carbon-Blanc, 33560, France

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GSK Investigational Site

Châtellerault, 86100, France

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GSK Investigational Site

Colombey-les-Belles, 54170, France

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GSK Investigational Site

Coulounieix-Chamiers, 24660, France

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GSK Investigational Site

Cournonterral, 34660, France

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GSK Investigational Site

Dessenheim, 68600, France

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GSK Investigational Site

Dijon, 21000, France

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GSK Investigational Site

Dinard, 35800, France

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GSK Investigational Site

Donges, 44480, France

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GSK Investigational Site

Ermont, 95124, France

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GSK Investigational Site

Fléville-devant-Nancy, 54710, France

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GSK Investigational Site

Gémenos, 13420, France

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GSK Investigational Site

Gondreville, 54840, France

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GSK Investigational Site

Grenay, 62160, France

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GSK Investigational Site

Guesnain, 59287, France

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GSK Investigational Site

Hatten, 67690, France

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GSK Investigational Site

Hinx, 40180, France

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GSK Investigational Site

La Bouëxière, 35340, France

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GSK Investigational Site

La Fôret Sur Sèvres, 79380, France

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GSK Investigational Site

La Riche, 37520, France

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GSK Investigational Site

Lambersart, 59130, France

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GSK Investigational Site

Laval, 53000, France

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GSK Investigational Site

Le Blanc-Mesnil, 93150, France

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GSK Investigational Site

Limoges, 87000, France

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GSK Investigational Site

Marseille, 13331, France

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GSK Investigational Site

Metz-Tessy, 74370, France

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GSK Investigational Site

Montauban, 82017, France

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GSK Investigational Site

Montpellier, 34070, France

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GSK Investigational Site

Montpellier, 34295, France

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GSK Investigational Site

Mûrs-Erigné, 49610, France

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GSK Investigational Site

Nancy, 54000, France

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GSK Investigational Site

Nantes, 44200, France

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GSK Investigational Site

Nantes, 44300, France

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GSK Investigational Site

Narbonne, 11100, France

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GSK Investigational Site

Nice, 06000, France

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GSK Investigational Site

Obernai, 67210, France

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GSK Investigational Site

Paris, 75020, France

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GSK Investigational Site

Perpignan, 66000, France

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GSK Investigational Site

Rosiers-d'Égletons, 19300, France

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GSK Investigational Site

Rouen, 76000, France

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GSK Investigational Site

Royaumeix, 54200, France

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GSK Investigational Site

Saint-Etienne, 42000, France

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GSK Investigational Site

Saint-Etienne, 42100, France

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GSK Investigational Site

Saint-Ouen-la-Rouërie, 35460, France

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GSK Investigational Site

Scorbé-Clairvaux, 86140, France

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GSK Investigational Site

Segré, 49500, France

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GSK Investigational Site

Soulac-sur-Mer, 33780, France

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GSK Investigational Site

Strasbourg, 67000, France

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GSK Investigational Site

Thouars, 79100, France

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GSK Investigational Site

Toul, 54200, France

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GSK Investigational Site

Toulon, 83000, France

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GSK Investigational Site

Toulouse, 31077, France

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GSK Investigational Site

Toulouse, 31300, France

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GSK Investigational Site

Verzy, 51380, France

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GSK Investigational Site

Vieux-Condé, 59690, France

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GSK Investigational Site

Villejuif, 94800, France

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GSK Investigational Site

Wattrelos, 59150, France

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GSK Investigational Site

Witry-lès-Reims, 51420, France

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GSK Investigational Site

Munich, Bavaria, 80339, Germany

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GSK Investigational Site

Munich, Bavaria, 81241, Germany

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GSK Investigational Site

Wallerfing, Bavaria, 94574, Germany

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GSK Investigational Site

Potsdam, Brandenburg, 14469, Germany

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GSK Investigational Site

Dortmund, North Rhine-Westphalia, 44263, Germany

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GSK Investigational Site

Rheine, North Rhine-Westphalia, 48431, Germany

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GSK Investigational Site

Delitzsch, Saxony, 04509, Germany

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GSK Investigational Site

Leipzg, Saxony, 04109, Germany

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GSK Investigational Site

Leipzig, Saxony, 04103, Germany

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GSK Investigational Site

Leipzig, Saxony, 04207, Germany

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GSK Investigational Site

Leipzig, Saxony, 04275, Germany

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GSK Investigational Site

Leipzig, Saxony, 04357, Germany

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GSK Investigational Site

Teuchern, Saxony-Anhalt, 6682, Germany

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GSK Investigational Site

Geesthacht, Schleswig-Holstein, 21502, Germany

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GSK Investigational Site

Schmölln, Thuringia, 04626, Germany

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GSK Investigational Site

Berlin, 10119, Germany

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GSK Investigational Site

Berlin, 10717, Germany

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GSK Investigational Site

Berlin, 10787, Germany

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GSK Investigational Site

Berlin, 13156, Germany

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GSK Investigational Site

Berlin, 14059, Germany

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GSK Investigational Site

Magdeburg, 39120, Germany

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Related Publications (1)

• Devillier P, Humbert M, Boye A, Zachgo W, Jacques L, Nunn C, West S, Nicholls A, Antoun Z, Spinu L, Grouin JM. Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI) versus twice-daily inhaled corticosteroids/long-acting beta2-agonists (ICS/LABA) in patients with uncontrolled asthma: An open-label, randomized, controlled trial. Respir Med. 2018 Aug;141:111-120. doi: 10.1016/j.rmed.2018.06.009. Epub 2018 Jun 9.

  PMID: 30053956 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

fluticasone furoate; vilanterol; Fluticasone; Salmeterol Xinafoate; Budesonide; Formoterol Fumarate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Pregnenediones; Pregnenes; Pregnanes

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 18, 2015
• Study Start: July 9, 2015
• Primary Completion: July 20, 2017
• Study Completion: July 20, 2017
• Last Updated: January 14, 2019
• Results First Posted: January 14, 2019

Record last verified: 2018-06

Locations

FR (72); DE (21)