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Study to Compare the Addition of Umeclidinium Bromide (UMEC) to Fluticasone Furoate (FF)/Vilanterol (VI), With Placebo Plus FF/VI in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

9. oktober 2017 opdateret af: GlaxoSmithKline

A Study to Compare the Addition of Umeclidinium Bromide (UMEC) to Fluticasone Furoate (FF)/Vilanterol (VI), With Placebo Plus FF/VI in Subjects With Chronic Obstructive Pulmonary Disease (COPD) -Study 1

After screening, subjects will enter a 4 week open-label run-in period with fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg administered once daily via dry powder inhaler (DPI). Subjects will then be randomized to receive any one of the 3 treatments (umeclidinium bromide [UMEC] [62.5 mcg] administered once daily via a DPI; OR UMEC [125 mcg] administered once daily via a DPI; OR matching placebo administered once daily via a DPI), while continuing treatment with open label FF/VI 100/25 mcg during a 12-week treatment period. There will be a total of eight scheduled clinic visits at Pre-Screening (Visit0), Screening (Visit 1), blinded treatment Day 1(Visit2), 2(Visit3), 28 (Visit4), 56 (Visit5), 84 (Visit6) and 85 (Visit7). A follow-up phone contact will be conducted approximately 7 days after the last clinic visit. The total duration of subject participation in the study from Screening to Follow-up will be approximately 17 weeks.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

619

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Argentina
      • Buenos Aires, Argentina, C1424BSF
        • GSK Investigational Site
      • Buenos Aires, Argentina, C1425BEN
        • GSK Investigational Site
      • Buenos Aires, Argentina, C1425FVH
        • GSK Investigational Site
      • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
        • GSK Investigational Site
      • Mendoza, Argentina, M5500CCG
        • GSK Investigational Site
      • Mendoza, Argentina, 5500
        • GSK Investigational Site
      • San Miguel de Tucumán, Argentina, 4000
        • GSK Investigational Site
  • Canada
      • Quebec, Canada, G1V 4G5
        • GSK Investigational Site
    • Manitoba
      • Winnipeg, Manitoba, Canada, R2K 3S8
        • GSK Investigational Site
    • Nova Scotia
      • Truro, Nova Scotia, Canada, B2N 1L2
        • GSK Investigational Site
    • Ontario
      • Sudbury, Ontario, Canada, P3E 1H5
        • GSK Investigational Site
      • Toronto, Ontario, Canada, M3H 5S4
        • GSK Investigational Site
      • Toronto, Ontario, Canada, M5G 1N8
        • GSK Investigational Site
      • Toronto, Ontario, Canada, M4V 1R3
        • GSK Investigational Site
    • Quebec
      • Gatineau, Quebec, Canada, J8Y 6S8
        • GSK Investigational Site
      • Mirabel, Quebec, Canada, J7J 2K8
        • GSK Investigational Site
      • Montreal, Quebec, Canada, H2R 1V6
        • GSK Investigational Site
      • St-Charles-Borromée, Quebec, Canada, J6E 2B4
        • GSK Investigational Site
      • St-Romulad, Quebec, Canada, G6W 5M6
        • GSK Investigational Site
  • Chile
      • Santiago, Chile, 8380453
        • GSK Investigational Site
      • Santiago, Chile, 8910131
        • GSK Investigational Site
      • Viña del Mar, Chile, 2520594
        • GSK Investigational Site
    • Región Del Biobio
      • Concepción, Región Del Biobio, Chile, 4070038
        • GSK Investigational Site
    • Región Metro De Santiago
      • Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
        • GSK Investigational Site
      • Santiago, Región Metro De Santiago, Chile, 7510186
        • GSK Investigational Site
      • Santiago, Región Metro De Santiago, Chile, 7500692
        • GSK Investigational Site
      • Santiago, Región Metro De Santiago, Chile, 7500710
        • GSK Investigational Site
      • Santiago, Región Metro De Santiago, Chile, 7880047
        • GSK Investigational Site
      • Santiago, Región Metro De Santiago, Chile, 8910131
        • GSK Investigational Site
      • Talca, Región Metro De Santiago, Chile, 3460001
        • GSK Investigational Site
    • Valparaíso
      • Quillota, Valparaíso, Chile, 2260000
        • GSK Investigational Site
  • Forenede Stater
    • Alabama
      • Jasper, Alabama, Forenede Stater, 35501
        • GSK Investigational Site
    • Florida
      • Clearwater, Florida, Forenede Stater, 33765-2616
        • GSK Investigational Site
      • Tampa, Florida, Forenede Stater, 33603
        • GSK Investigational Site
    • Louisiana
      • New Orleans, Louisiana, Forenede Stater, 70115
        • GSK Investigational Site
    • Missouri
      • Saint Louis, Missouri, Forenede Stater, 63141
        • GSK Investigational Site
    • Oregon
      • Medford, Oregon, Forenede Stater, 97504
        • GSK Investigational Site
    • South Carolina
      • Easley, South Carolina, Forenede Stater, 29640
        • GSK Investigational Site
      • Greenville, South Carolina, Forenede Stater, 29615
        • GSK Investigational Site
      • Spartanburg, South Carolina, Forenede Stater, 29303
        • GSK Investigational Site
      • Union, South Carolina, Forenede Stater, 29379
        • GSK Investigational Site
    • Texas
      • San Antonio, Texas, Forenede Stater, 78229
        • GSK Investigational Site
    • Virginia
      • Abingdon, Virginia, Forenede Stater, 24210
        • GSK Investigational Site
    • West Virginia
      • Morgantown, West Virginia, Forenede Stater, 26505
        • GSK Investigational Site
  • Rumænien
      • Bacau, Rumænien, 600252
        • GSK Investigational Site
      • Bucharest, Rumænien, 020125
        • GSK Investigational Site
      • Bucuresti, Rumænien, 010457
        • GSK Investigational Site
      • Bucuresti, Rumænien, 030303
        • GSK Investigational Site
      • Cluj Napoca, Rumænien, 400371
        • GSK Investigational Site
      • Codlea, Rumænien, 505100
        • GSK Investigational Site
      • Ramnicu Valcea, Rumænien, 240564
        • GSK Investigational Site
      • Suceava, Rumænien, 720284
        • GSK Investigational Site
      • Timisoara, Rumænien, 300310
        • GSK Investigational Site

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

40 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Type of subject: Outpatient.
  • Informed Consent: A signed and dated written informed consent prior to study participation.
  • Age: Subjects 40 years of age or older at Visit 1.
  • Gender: Male or female subjects.
  • A female is eligible to enter and participate in the study if she is of:
  • Non-child bearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g., age appropriate, >45 years, in the absence of hormone replacement therapy.

OR

  • Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact):
  • Abstinence
  • Oral Contraceptive, either combined or progestogen alone
  • Injectable progestogen
  • Implants of levonorgestrel
  • Estrogenic vaginal ring
  • Percutaneous contraceptive patches
  • Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label
  • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, "documented" refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records.
  • Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
  • Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
  • Smoking History: Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years [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)]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to calculate pack year history.
  • Severity of Disease: A pre and post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a pre and post-albuterol/salbutamol FEV1 of <=70% of predicted normal values at Visit 1 (Screening) calculated using Nutrition Health and Examination Survey (NHANES) III reference equations.
  • Dyspnea: A score of >=2 on the mMRC Dyspnea Scale at Visit 1.
  • QTc Criteria:
  • QTc(F) <450 milliseconds (msec) or
  • QTc(F) <480msec for patients with QRS duration >=120msec
  • The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread.
  • For subject eligibility and withdrawal, QTcF will be used.
  • For purposes of data analysis, QTcF will be used as primary.
  • The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.

Exclusion Criteria:

  • Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
  • Asthma: A current diagnosis of asthma.
  • Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
  • Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for <5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). 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.
  • Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) lactose/milk protein or magnesium stearate, or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction, that, in the opinion of the study physician contraindicates study participation or use of an inhaled Long acting muscarinic antagonist (LAMA), Long acting beta agonist (LABA) or Inhaled corticosteroids (ICS).
  • Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
  • Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.
  • Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
  • 12-Lead ECG: An abnormal and clinical significant ECG finding from the 12-lead ECG conducted at Visit 1. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The study investigator will determine the medical significance of any ECG abnormalities.
  • Clinically significant and abnormal laboratory finding at Screening (Visit1). After discussion with the Medical Monitor, the investigator may have the option to verify the abnormal lab result prior to Visit2
  • Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
  • Excluded Medications: Use of the following medications are not permitted within the defined time intervals prior to Visit 1and throughout the study:
  • No use within 12 weeks prior to Screening Visit 1 or thereafter at any time during the study: Depot corticosteroids.
  • No use within 6 weeks prior to Screening Visit 1 or thereafter at any time during the study: Systemic, oral or parenteral corticosteroids (Intra-articular corticosteroid injections are permitted.), Antibiotics (for lower respiratory tract infection), Cytochrome P450 3A4 strong inhibitors.
  • No use within 14 days prior to Screening Visit 1 or thereafter at any time during the study: Phosphodiesterase 4 inhibitors (roflumilast).
  • No use within 10 days prior to Screening Visit 1 or thereafter at any time during the study: Olodaterol and Indacaterol.
  • No use within 7 days prior to Screening Visit 1 or thereafter at any time during the study: Long acting muscarinici antagonists (tiotropium, aclidinium, glycopyrronium).
  • No use within 48 hrs prior to Screening Visit 1 or thereafter at any time during the study: Theophyllines, Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton), Salmeterol and formoterol, ICS/LABA combinations (e.g., fluticasone propionate/salmeterol, mometasone furoate/formoterol fumarate, budesonide/formoterol fumarate), Oral beta2-agonists Long-acting.
  • No use within 24 hrs prior to Screening Visit 1 or thereafter at any time during the study: Inhaled sodium cromoglycate or nedocromil sodium.
  • No use within 12 hrs prior to Screening Visit 1 or thereafter at any time during the study: Oral beta2-agonists Short-acting.
  • No use within 4 hrs prior to Screening Visit 1 or thereafter at any time during the study: Inhaled short acting beta2-agonists (use of study provided prn albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing.), Inhaled short-acting anticholinergics, Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products.
  • No use within 30 days or 5 half lives whichever is longer prior to Screening Visit 1 or thereafter at any time during the study: Any other investigational drug.
  • Prior enrolment in one of the replicate studies: subjects who have previously been assigned a subject number (enrolled) in study 200110 that is a replicate study of 200109.
  • Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., <=12 hours per day) is not exclusionary.
  • Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy.
  • Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1, or who will enter the acute phase of a pulmonary rehabilitation program during the study. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
  • Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
  • Affiliation with Investigator Site: 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.
  • Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: FF/VI 100/25 mcg + UMEC (62.5mcg)
Subjects received one inhalation of FF/VI 100/25 mcg via a DPI followed by one inhalation UMEC (62.5mcg) via DPI once-daily in the morning for 12 weeks.
Medicin: FF
Tørt hvidt pulver indeholdende 100 mcg Fluticasone Furoat blandet med lactose pr. blister blev indgivet af DPI.
Medicin: VI
Tørt hvidt pulver indeholdende 25 mcg Vilanterol mikroniseret lægemiddel (som 'M' salt triphenylacetat) blandet med lactose og magnesiumstearat pr. blister blev administreret af DPI.
Medicin: UMEC
Umeclidiniumbromid i en pulverblanding med lactose og magnesiumstearat blev brugt i to forskellige doser 62,5mcg og 125mcg.
Eksperimentel: FF/VI 100/25 mcg + UMEC (125 mcg)
Forsøgspersonerne fik én inhalation af FF/VI 100/25 mcg via DPI efterfulgt af én inhalation af UMEC (125mcg) via en DPI én gang dagligt om morgenen i 12 uger.
Medicin: FF
Tørt hvidt pulver indeholdende 100 mcg Fluticasone Furoat blandet med lactose pr. blister blev indgivet af DPI.
Medicin: VI
Tørt hvidt pulver indeholdende 25 mcg Vilanterol mikroniseret lægemiddel (som 'M' salt triphenylacetat) blandet med lactose og magnesiumstearat pr. blister blev administreret af DPI.
Medicin: UMEC
Umeclidiniumbromid i en pulverblanding med lactose og magnesiumstearat blev brugt i to forskellige doser 62,5mcg og 125mcg.
Eksperimentel: FF/VI 100/25 mcg + placebo
Forsøgspersonerne fik én inhalation af FF/VI 100/25 mcg via DPI efterfulgt af én inhalation af matchende placebo via en DPI én gang dagligt om morgenen i 12 uger.
Medicin: FF
Tørt hvidt pulver indeholdende 100 mcg Fluticasone Furoat blandet med lactose pr. blister blev indgivet af DPI.
Medicin: VI
Tørt hvidt pulver indeholdende 25 mcg Vilanterol mikroniseret lægemiddel (som 'M' salt triphenylacetat) blandet med lactose og magnesiumstearat pr. blister blev administreret af DPI.
Medicin: Placebo
Den matchende placebo DPI er identisk i udseende med inhalatoren, der indeholder aktiv undersøgelsesmedicin.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Ændring fra baseline (BL) i gennemtvunget eksspiratorisk volumen på et sekund (FEV1) på dag 85
Tidsramme: Dag 85
FEV1 er et mål for lungefunktionen og er defineret som den maksimale mængde luft, der kan udåndes kraftigt på et sekund. Laveste FEV1 på dag 85 er defineret som gennemsnittet af FEV1-værdierne opnået 23 og 24 timer efter dosering på dag 84. Analyse blev udført ved hjælp af en blandet model gentaget mål (MMRM) med kovariater af behandling, baseline FEV1, rygestatus, dag, behandling, dag for baseline interaktion og dag for behandling interaktion, dag er nominel. Baseline FEV1 er gennemsnittet af de to vurderinger foretaget efter 30 og 5 minutter (min) før dosis på dag 1. Ændringen fra basisværdien er forskellen mellem værdien under behandling og basisværdien.
Dag 85

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Ændring fra baseline i vægtet gennemsnit (WM), 0-6 timers FEV1 opnået efter dosis på dag 84
Tidsramme: Dag 84
FEV1 er et mål for lungefunktionen og er defineret som den maksimale mængde luft, der kan udåndes kraftigt på et sekund. Det 0-6 timers vægtede gennemsnit blev udledt ved at beregne arealet under FEV1/tidskurven over de nominelle tidspunkter på 0 timer (trough-værdi), 15 og 30 min, 1, 3 og 6 timer ved hjælp af trapezreglen, og derefter dividere med den faktiske tid mellem dosering og 6 timers vurderingen. Analyse blev udført ved hjælp af MMRM med kovariater af behandling, baseline FEV1 (gennemsnit af de to vurderinger foretaget 30 minutter og 5 minutter før dosis på dag 1), rygestatus, dag og dag for baseline og dag efter behandlingsinteraktioner. Baseline FEV1 er gennemsnittet af de to vurderinger foretaget ved 30 og 5 minutter før dosis på dag 1. Ændringen fra basisværdien er forskellen mellem værdien under behandling og basisværdien.
Dag 84

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

GlaxoSmithKline

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. oktober 2013

Primær færdiggørelse (Faktiske)

1. april 2014

Studieafslutning (Faktiske)

1. april 2014

Datoer for studieregistrering

Først indsendt

4. oktober 2013

Først indsendt, der opfyldte QC-kriterier

4. oktober 2013

Først opslået (Skøn)

8. oktober 2013

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

9. november 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

9. oktober 2017

Sidst verificeret

1. oktober 2017

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 200109

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

Ja

IPD-planbeskrivelse

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Studiedata/dokumenter

  1. Datasætspecifikation
    Informations-id: 200109
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  2. Individuelt deltagerdatasæt
    Informations-id: 200109
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  3. Studieprotokol
    Informations-id: 200109
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  4. Formular til informeret samtykke
    Informations-id: 200109
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  5. Annoteret sagsbetænkningsformular
    Informations-id: 200109
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  6. Statistisk analyseplan
    Informations-id: 200109
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  7. Klinisk undersøgelsesrapport
    Informations-id: 200109
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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