Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

Phase IV O2 Consumption Study in COPD Patients.

27. juli 2018 oppdatert av: AstraZeneca

A Phase 4, Randomized, Double-blind, Multicenter, Placebo-Controlled Two Way Cross-Over Study to Evaluate Changes in Oxygen Consumption and Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Symbicort pMDI 160/4.5 μg.

A Phase IV study evaluating changes in oxygen consumption and cardiac function in Subjects with Chronic obstructive pulmonary disease (COPD) with resting hyperinflation after administration of Symbicort pMDI 160/4.5 μg.

Studieoversikt

Detaljert beskrivelse

Patients with moderate/severe COPD are known to have static hyperinflation and to develop dynamic hyperinflation during exercise. Treatment with inhaled long-acting beta agonists and combination of the long-acting beta agonist (LABA), formoterol and the inhaled corticosteroid, budesonide has been shown to improve IC and decrease lung hyperinflation. In a similar previous pilot single centre study with budesonide/formoterol (Symbicort®) the analysis of cardiac outcomes demonstrated a decrease in maximum volume of oxygen (VO2) compared to placebo. Findings suggested that the use of Symbicort can decrease the cost of breathing and therefore reduce the cardiac demand experienced by COPD patients with hyperinflation at rest. The aim of this study is to investigate whether Symbicort therapy can decrease resting VO2 by decreasing static lung hyperinflation in subjects with COPD and to evaluate changes in cardiac function.

Studietype

Intervensjonell

Registrering (Faktiske)

51

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • Connecticut
      • Hartford, Connecticut, Forente stater, 06105
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02115
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, Forente stater, 28207
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19140
        • Research Site
    • South Carolina
      • Spartanburg, South Carolina, Forente stater, 29303
        • Research Site

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

40 år til 80 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Signing of the informed consent form (ICF) prior to any study specific procedures, including withholding of medications.
  2. Male or female, aged 40 to 80 years, inclusive, at Screening (Visit 1).
  3. Has a clinical diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines with a post bronchodilator FEV1/FVC <0.7 at Screening (Visit 1).
  4. Has a post-bronchodilator FEV1 ≤65% of predicted value at Screening (Visit 1). National Health and Nutrition Examination Survey (NHANES) predicted normal standards will be used for all subjects.
  5. Has an increase in IC of >10% after the administration of 1 inhalation of open-label Symbicort pMDI administered with a spacer at Screening (Visit 1).
  6. Has a cigarette smoking history of more than 10 pack-years (number of cigarettes smoked per day × number of years smoked)/20).
  7. Be able to understand and comply with study requirements, as judged by the Investigator.

Exclusion Criteria:

  1. Subject is an employee or relative of an employee involved in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  2. Previous enrollment or randomization in this study.
  3. Participation in another clinical study with an investigational product (IP) during the last 30 days prior to Screening (Visit 1).
  4. Subjects who are unable to discontinue their regular chronic COPD medications (including LAMAs and/or LABA/ICS) and/or who are unable or unwilling to comply with study requirements.
  5. Subjects who are taking uLABAs (indacaterol, vilanterol) or uLABA-containing products.
  6. Subjects who are taking PDE-4 inhibitors (roflumilast).
  7. Subjects who are taking oral corticosteroids on a chronic, regular basis.
  8. Subjects using daytime oxygen therapy.
  9. Subjects who are currently pregnant (confirmed with positive pregnancy test) or breast feeding.
  10. History of respiratory tract infection (including the upper respiratory tract) and/or pulmonary exacerbation within 6 weeks prior to Screening (Visit 1).
  11. Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening (Visit 1), or history of lung transplantation, or, in the Investigator's opinion, the subject may need thoracotomy or other lung surgery during the study.
  12. History or current diagnosis of asthma and/or alpha 1 anti-trypsin deficiency.
  13. Known active tuberculosis.
  14. History of interstitial lung or massive pulmonary thromboembolic disease.
  15. History of bronchiectasis secondary to respiratory diseases other than COPD (eg, cystic fibrosis, Kartagener's syndrome, etc).
  16. Any clinically significant disease or disorder (eg, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, major physical impairment) which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results of the study, or may affect the subject's ability to participate in the study.
  17. Recent (within 12 months prior to Screening [Visit 1]) history of myocardial infarction, recent history of heart failure (New York Heart Association [NYHA] class III and IV, pulmonary edema, and/or cardiac arrhythmia.
  18. Previous or current history of lung cancer.
  19. History of cancer (within 5 years prior to Visit 1), except for non-metastatic, non melanoma skin cancer.
  20. Subjects who cannot perform spirometry manuevers or tolerate body plethysmography.
  21. Subjects with known hypersensitivity to Symbicort, its monocomponents (budesonide or formoterol), or its excipients.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Crossover-oppdrag
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Symbicort pressurized Metered Dose Inhaler (pMDI)
Subjects will receive a single dose (2 inhalations) of Symbicort pMDI 160/4.5 μg (2 inhalations; total dosage 320/9.0 μg) or placebo (with a spacer) in a cross-over design (a total of 2 doses of Symbicort and 2 doses of placebo over the duration of the study), and assessments will be made before and after dosing at specified timepoints
Placebo komparator: Placebo of reference drug
Placebo will be given according at the same dose and schedule as the active comparator - cross-over design.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Consumption (VO2; Obtained Via a Metabolic Cart)
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Pulse (Defined as VO2/Heart Rate [HR]; VO2 is Obtained Via a Metabolic Cart; Used as a Surrogate for Stroke Volume)
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter HR
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2)to Post-dose (Visit 5) Assessment in Spirometry.
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and IC (using an slow vital capacity [SVC] maneuver; IC/total lung capacity [TLC] will be used as a measure of resting hyperinflation). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Vt/Ti
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in mean inspiratory flow (tidal volume [Vt]/inspiratory time [Ti]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in the Modified Borg Scale for Dyspnea
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). Modified Borg scale for dyspnea was self-administered at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21). The Borg scale is a 1-item instrument through which a subject reports dyspnea symptoms on a scale of 0-10 to quantify the intensity of dyspnea (where 10 is most intense).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter VCO2
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter SaO2
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in RR
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Ti/Ttot
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in fractional inspiratory time (Ti/total cycle time [Ttot]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Vt
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in tidal volume (Vt). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Ve
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in minute ventilation (Ve). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Spirometry.
Tidsramme: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
FEV1/FVC. For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

25. august 2015

Primær fullføring (Faktiske)

12. august 2016

Studiet fullført (Faktiske)

12. august 2016

Datoer for studieregistrering

Først innsendt

30. juli 2015

Først innsendt som oppfylte QC-kriteriene

25. august 2015

Først lagt ut (Anslag)

26. august 2015

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

30. juli 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

27. juli 2018

Sist bekreftet

1. juli 2018

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere