March 23, 2020
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March 25, 2020
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April 18, 2024
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April 28, 2022
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December 2024 (Final data collection date for primary outcome measure)
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Change from baseline in pre-dose morning Forced Expiratory Volume in the 1st second (FEV1) at Week 28 [ Time Frame: Week 28 ]
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Same as current
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|
- Change from baseline in 2-hour post-dose morning FEV1 at Week 28 [ Time Frame: Week 28 ]
- Rate of moderate and severe COPD exacerbations over 52 weeks of treatment [ Time Frame: 52-week treatment period ]
Annualized rate of moderate and severe COPD exacerbations as observed during the 52-week study treatment period.
- Change from baseline in pre-dose morning FEV1 at designated clinic visits [ Time Frame: Week 4, Week 10, Week 40, & Week 52 ]
- Change from baseline in 2-hour post-dose morning FEV1 designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 40, & Week 52 ]
- Change from pre-dose to 2-hour post-dose morning FEV1 at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- FEV1 response (change from baseline in pre-dose morning FEV1 ≥100ml) at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Time to first moderate or severe COPD exacerbation [ Time Frame: 52-week treatment period ]
- Rate of severe COPD exacerbations over 52 weeks of treatment [ Time Frame: 52-week treatment period ]
Annualized rate of severe COPD exacerbations as observed during 52-week treatment period
- Time to first severe COPD exacerbation [ Time Frame: 52-week treatment period ]
- Saint George's Respiratory Questionnaire (SGRQ) response (a decrease from baseline in total score ≥4) at designated clinic visits [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline in the SGRQ total score and domain scores at each designated clinic visit [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline to each inter-visit period in the percentage of days without intake of rescue medication [ Time Frame: Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52 ]
Change from baseline (defined as the 2-week run-in period prior to randomization) to each inter-visit period (defined as the period of time between designated clinic visits) in percentage of days without rescue medication
- Change from baseline to each inter-visit period in the average use of rescue medication (number of puffs/day) [ Time Frame: Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52 ]
Change from baseline (defined as the 2-week run-in period prior to randomization) in the average number of puffs per day of rescue medication for each inter-visit period (defined as the period of time between designated clinic visits).
- Change from baseline in pre-dose morning Forced Vital Capacity (FVC) at designated clinic visits [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline in 2-hour post-dose morning FVC at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
Change from baseline (defined as the pre-dose value on Day 1) in 2-hour post-dose morning FVC at designated clinic visits
- Change from pre-dose to 2-hour post-dose morning FVC at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline to each inter-visit period in the average E-RS total score and domain scores [ Time Frame: Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52 ]
Change from baseline (defined as the 2-week run-in period prior to randomization) in the average E-RS total score and E-RS domain scores for the period of time between designated clinic visits.
- Change from baseline in COPD Assessment Test (CAT) score at designated clinic visit [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
The CAT is composed of 8 questions to measure the impact of COPD on daily life, which are scored from 0 to 5 with higher scores reflecting greater impact.
- CAT response (decrease from baseline ≥2 points) at designated clinic visits [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Modified Medical Research Council (mMRC) dyspnea scale at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
Descriptive statistics of the mMRC dyspnea scale score at designated clinic visits. The mMRC dyspnea scale is graded from 0 to 4, with higher grades reflecting greater severity.
- Change from baseline in health-related quality of life (decrease from baseline in total SGRQ score ≥4) over 52 weeks of treatment. [ Time Frame: 52-week treatment period ]
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- Change from baseline in 2-hour post-dose morning FEV1 at Week 28 [ Time Frame: Week 28 ]
- Rate of moderate and severe COPD exacerbations over 52 weeks of treatment [ Time Frame: 52-week treatment period ]
Annualized rate of moderate and severe COPD exacerbations as observed during the 52-week study treatment period.
- Change from baseline in pre-dose morning FEV1 at designated clinic visits [ Time Frame: Week 4, Week 10, Week 40, & Week 52 ]
- Change from baseline in 2-hour post-dose morning FEV1 designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 40, & Week 52 ]
- Change from pre-dose to 2-hour post-dose morning FEV1 at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- FEV1 response (change from baseline in pre-dose morning FEV1 ≥100ml) at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Time to first moderate or severe COPD exacerbation [ Time Frame: 52-week treatment period ]
- Rate of severe COPD exacerbations over 52 weeks of treatment [ Time Frame: 52-week treatment period ]
Annualized rate of severe COPD exacerbations as observed during 52-week treatment period
- Time to first severe COPD exacerbation [ Time Frame: 52-week treatment period ]
- Saint George's Respiratory Questionnaire (SGRQ) response (a decrease from baseline in total score ≥4) at designated clinic visits [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline in the SGRQ total score and domain scores at each designated clinic visit [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline to each inter-visit period in the percentage of days without intake of rescue medication [ Time Frame: Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52 ]
Change from baseline (defined as the 2-week run-in period prior to randomization) to each inter-visit period (defined as the period of time between designated clinic visits) in percentage of days without rescue medication
- Change from baseline to each inter-visit period in the average use of rescue medication (number of puffs/day) [ Time Frame: Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52 ]
Change from baseline (defined as the 2-week run-in period prior to randomization) in the average number of puffs per day of rescue medication for each inter-visit period (defined as the period of time between designated clinic visits).
- Change from baseline in pre-dose morning Forced Vital Capacity (FVC) at designated clinic visits [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline in 2-hour post-dose morning FVC at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
Change from baseline (defined as the pre-dose value on Day 1) in 2-hour post-dose morning FVC at designated clinic visits
- Change from pre-dose to 2-hour post-dose morning FVC at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- Change from baseline to each inter-visit period in the average E-RS total score and domain scores [ Time Frame: Day 1-Week 4, Week 4-Week 10, Week 10-Week 28, Week 28-Week 40, Week 40-Week 52 ]
Change from baseline (defined as the 2-week run-in period prior to randomization) in the average E-RS total score and E-RS domain scores for the period of time between designated clinic visits.
- Change from baseline in COPD Assessment Test (CAT) score at designated clinic visit [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- CAT response (decrease from baseline ≥2 points) at designated clinic visits [ Time Frame: Week 4, Week 10, Week 28, Week 40, & Week 52 ]
- mMRC dyspnea scale at designated clinic visits [ Time Frame: Day 1, Week 4, Week 10, Week 28, Week 40, & Week 52 ]
Descriptive statistics of the mMRC dyspnea scale score at designated clinic visits
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Not Provided
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Not Provided
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|
A Study Comparing Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination CHF 5993 With the Fixed Dose Dual Combination CHF 1535 in Subjects With COPD
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A Phase III, 52-week, Multinational, Multicenter, Randomized, Double-blind, 2-arm Parallel Group Study Comparing Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate Plus Glycopyrronium Bromide (CHF 5993) With the Fixed Dose Dual Combination of Beclomethasone Dipropionate Plus Formoterol Fumarate (CHF 1535), Both Administered Via pMDI in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
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The purpose of this study is to compare CHF 5993 with CHF 1535 in improving lung function, reducing moderate and severe COPD exacerbations, and other clinical efficacy and safety outcomes in the target subject population.
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This is a phase III, multinational, multicenter, randomized, double-blind active controlled 2-arm parallel group study to compare efficacy, safety, and tolerability of CHF 5993 pMDI with CHF 1535 pMDI with respect to lung function, incidence of moderate and severe COPD exacerbations, and other clinical efficacy and safety outcomes.
After screening, eligible subjects will enter 2-week run-in period using their regular COPD maintenance therapies after which they will be randomized to one of 2 study treatment groups. Following randomization, subjects will be assessed after 4 weeks then at 6-week intervals thereafter for a period of 52 weeks. A follow-up safety phone call will be performed a week after the last clinic visit. A subset of subjects consenting to participate in the pharmacokinetic substudy will undergo additional assessments (totaling 3 visits) during the scheduled study visits.
During the study, daily symptoms, rescue medication use and compliance with the study drug will be recorded via a subject electronic diary. Subject concomitant medications, adverse events, and healthcare resource utilization will be assessed and recorded throughout the study. At intermittent study visits, subjects will undergo vital signs examinations including weight, spirometry measurements, and 12-lead ECG. Symptoms and COPD health status will be assessed through disease specific questionnaires. Routine hematology, blood chemistry, and serum pregnancy testing will be performed before enrollment and at end of study.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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- Drug: Beclomethasone Dipropionate
Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5μg and BDP/FF 100/6μg
Other Name: BDP
- Drug: Glycopyrronium Bromide
Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5μg
- Drug: Formoterol Fumarate
Available in pressurized inhalation solution BDP/FF/GB 100/6/12.5μg and BDP/FF 100/6μg
Other Name: FF
|
- Experimental: BDP/FF/GB - CHF 5993
Two inhalations twice daily of BDP/FF/GB (100/6/12.5μg) for a period of 52 weeks via pressurized metered dose inhaler
Interventions:
- Drug: Beclomethasone Dipropionate
- Drug: Glycopyrronium Bromide
- Drug: Formoterol Fumarate
- Active Comparator: BDP/FF - CHF 1535
Two inhalations twice daily of BDP/FF (100/6μg) for a period of 52 weeks via pressurized metered dose inhaler
Interventions:
- Drug: Beclomethasone Dipropionate
- Drug: Formoterol Fumarate
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- Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324-43. doi: 10.1183/09031936.00080312. Epub 2012 Jun 27.
- Lopez AD, Shibuya K, Rao C, Mathers CD, Hansell AL, Held LS, Schmid V, Buist S. Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J. 2006 Feb;27(2):397-412. doi: 10.1183/09031936.06.00025805. No abstract available.
- Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De Leon FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2095-128. doi: 10.1016/S0140-6736(12)61728-0. Erratum In: Lancet. 2013 Feb 23;381(9867):628. AlMazroa, Mohammad A [added]; Memish, Ziad A [added].
- Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442. doi: 10.1371/journal.pmed.0030442.
- Montes de Oca M, Perez-Padilla R, Talamo C, Halbert RJ, Moreno D, Lopez MV, Muino A, Jose Roberto BJ, Valdivia G, Pertuze J, Ana Maria BM; PLATINO Team. Acute bronchodilator responsiveness in subjects with and without airflow obstruction in five Latin American cities: the PLATINO study. Pulm Pharmacol Ther. 2010 Feb;23(1):29-35. doi: 10.1016/j.pupt.2009.09.005. Epub 2009 Oct 8.
- Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999 Jul;54(7):581-6. doi: 10.1136/thx.54.7.581.
- Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509.
- Lane DC, Stemkowski S, Stanford RH, Tao Z. Initiation of Triple Therapy with Multiple Inhalers in Chronic Obstructive Pulmonary Disease: An Analysis of Treatment Patterns from a U.S. Retrospective Database Study. J Manag Care Spec Pharm. 2018 Nov;24(11):1165-1172. doi: 10.18553/jmcp.2018.24.11.1165.
- Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, Dransfield MT, Halpin DMG, Han MK, Jones CE, Kilbride S, Lange P, Lomas DA, Martinez FJ, Singh D, Tabberer M, Wise RA, Pascoe SJ; IMPACT Investigators. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. N Engl J Med. 2018 May 3;378(18):1671-1680. doi: 10.1056/NEJMoa1713901. Epub 2018 Apr 18.
- Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, Kessler R. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009 Oct 15;180(8):741-50. doi: 10.1164/rccm.200904-0492OC. Epub 2009 Jul 30.
- Hanania NA, Crater GD, Morris AN, Emmett AH, O'Dell DM, Niewoehner DE. Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD. Respir Med. 2012 Jan;106(1):91-101. doi: 10.1016/j.rmed.2011.09.002. Epub 2011 Oct 29.
- Jung KS, Park HY, Park SY, Kim SK, Kim YK, Shim JJ, Moon HS, Lee KH, Yoo JH, Lee SD; Korean Academy of Tuberculosis and Respiratory Diseases study group; Korea Chronic Obstructive Pulmonary Disease study group. Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: a randomized controlled study. Respir Med. 2012 Mar;106(3):382-9. doi: 10.1016/j.rmed.2011.09.004. Epub 2011 Oct 4.
- Lipson DA, Barnacle H, Birk R, Brealey N, Locantore N, Lomas DA, Ludwig-Sengpiel A, Mohindra R, Tabberer M, Zhu CQ, Pascoe SJ. FULFIL Trial: Once-Daily Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Aug 15;196(4):438-446. doi: 10.1164/rccm.201703-0449OC.
- Ferguson GT, Rabe KF, Martinez FJ, Fabbri LM, Wang C, Ichinose M, Bourne E, Ballal S, Darken P, DeAngelis K, Aurivillius M, Dorinsky P, Reisner C. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial. Lancet Respir Med. 2018 Oct;6(10):747-758. doi: 10.1016/S2213-2600(18)30327-8. Epub 2018 Sep 16. Erratum In: Lancet Respir Med. 2018 Oct 4;: Lancet Respir Med. 2019 Feb;7(2):e9.
- Singh D, Papi A, Corradi M, Pavlisova I, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting beta2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016 Sep 3;388(10048):963-73. doi: 10.1016/S0140-6736(16)31354-X. Epub 2016 Sep 1.
- Vestbo J, Papi A, Corradi M, Blazhko V, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, Singh D. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Lancet. 2017 May 13;389(10082):1919-1929. doi: 10.1016/S0140-6736(17)30188-5. Epub 2017 Apr 3.
- Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, Guasconi A, Montagna I, Vezzoli S, Petruzzelli S, Scuri M, Roche N, Singh D. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018 Mar 17;391(10125):1076-1084. doi: 10.1016/S0140-6736(18)30206-X. Epub 2018 Feb 9. Erratum In: Lancet. 2018 Feb 26;:
- Wedzicha JA, Singh D, Vestbo J, Paggiaro PL, Jones PW, Bonnet-Gonod F, Cohuet G, Corradi M, Vezzoli S, Petruzzelli S, Agusti A; FORWARD Investigators. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014 Aug;108(8):1153-62. doi: 10.1016/j.rmed.2014.05.013. Epub 2014 Jun 6. Erratum In: Respir Med. 2015 Mar;109(3):434-5.
- Jones PW, Tabberer M, Chen WH. Creating scenarios of the impact of COPD and their relationship to COPD Assessment Test (CAT) scores. BMC Pulm Med. 2011 Aug 11;11:42. doi: 10.1186/1471-2466-11-42.
- Mullerova H, Dransfield MT, Thomashow B, Jones PW, Rennard S, Karlsson N, Fageras M, Metzdorf N, Petruzzelli S, Rommes J, Sciurba FC, Tabberer M, Merrill D, Tal-Singer R. Clinical Development and Research Applications of the Chronic Obstructive Pulmonary Disease Assessment Test. Am J Respir Crit Care Med. 2020 May 1;201(9):1058-1067. doi: 10.1164/rccm.201907-1369PP. No abstract available.
- Kon SS, Canavan JL, Jones SE, Nolan CM, Clark AL, Dickson MJ, Haselden BM, Polkey MI, Man WD. Minimum clinically important difference for the COPD Assessment Test: a prospective analysis. Lancet Respir Med. 2014 Mar;2(3):195-203. doi: 10.1016/S2213-2600(14)70001-3. Epub 2014 Feb 4.
- Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
- Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, van der Grinten C, Gustafsson P, Jensen R, Macintyre N, McKay RT, Pedersen OF, Pellegrino R, Viegi G, Wanger J. Standardisation of lung function testing: the authors' replies to readers' comments. Eur Respir J. 2010 Dec;36(6):1496-8. doi: 10.1183/09031936.00130010. No abstract available.
- Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987 Feb;106(2):196-204. doi: 10.7326/0003-4819-106-2-196.
- Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1418-22. doi: 10.1164/ajrccm.157.5.9709032.
- Jones PW. St. George's Respiratory Questionnaire: MCID. COPD. 2005 Mar;2(1):75-9. doi: 10.1081/copd-200050513.
- Jones P, Lareau S, Mahler DA. Measuring the effects of COPD on the patient. Respir Med. 2005 Dec;99 Suppl B:S11-8. doi: 10.1016/j.rmed.2005.09.011. Epub 2005 Oct 19.
- Jones PW, Gelhorn H, Wilson H, Karlsson N, Menjoge S, Mullerova H, Rennard SI, Tal-Singer R, Merrill D, Tabberer M. Responder Analyses for Treatment Effects in COPD Using the St George's Respiratory Questionnaire. Chronic Obstr Pulm Dis. 2017 Mar 2;4(2):124-131. doi: 10.15326/jcopdf.4.2.2017.0130.
- Roland NJ, Bhalla RK, Earis J. The local side effects of inhaled corticosteroids: current understanding and review of the literature. Chest. 2004 Jul;126(1):213-9. doi: 10.1378/chest.126.1.213.
- Ellepola AN, Samaranayake LP. Inhalational and topical steroids, and oral candidosis: a mini review. Oral Dis. 2001 Jul;7(4):211-6.
- Roger JH, Bratton DJ, Mayer B, Abellan JJ, Keene ON. Treatment policy estimands for recurrent event data using data collected after cessation of randomised treatment. Pharm Stat. 2019 Jan;18(1):85-95. doi: 10.1002/pst.1910. Epub 2018 Nov 8.
- Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002 Mar;35(3):716-21. doi: 10.1053/jhep.2002.31250.
- Bajaj JS, Cordoba J, Mullen KD, Amodio P, Shawcross DL, Butterworth RF, Morgan MY; International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN). Review article: the design of clinical trials in hepatic encephalopathy--an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther. 2011 Apr;33(7):739-47. doi: 10.1111/j.1365-2036.2011.04590.x. Epub 2011 Feb 9.
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Recruiting
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2934
|
Same as current
|
December 2024
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December 2024 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Signed and dated written informed consent must be obtained prior to initiating any study-related procedures
- Outpatient
- Male or female subjects aged ≥40 years
-
Female subjects:
- WOCBP fulfilling one of the following criteria: i. WOCBP with fertile male partners: they and/or their partner must be willing to use a highly effective birth control method from the signing of the informed consent form and until the follow-up contact or ii. WOCBP with non-fertile male partners (contraception is not required in this case).
- Female subjects of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e. post-menopausal or permanently sterile as per definitions given in Appendix 5). Tubal ligation or partial surgical interventions are not acceptable. If indicated, as per investigator's request, post-menopausal status may be confirmed by follicle-stimulating hormone levels (according to local laboratory ranges)
- COPD diagnosis for at least 12 months before the screening visit in accordance with the definition by the GOLD 2020 Report
- Current or ex-smokers who quit smoking at least 6 months prior to screening with a smoking history of at least 10 pack-years [pack-years = (number of cigarettes per day x number of years)/20]
- COPD Assessment Test (CAT) score ≥10
- A pre- and post-bronchodilator FEV1/FVC ratio <0.70 at screening
- A post-bronchodilator FEV1 <50% predicted normal at screening and a documented history of ≥1 moderate or severe COPD exacerbation in the previous 12 months OR a post-bronchodilator FEV1 ≥50% and <80% of predicted normal at screening and a documented history of ≥2 moderate COPD exacerbations or ≥1 severe COPD exacerbation in the previous 12 months
- Subjects receiving daily inhaled maintenance therapy for their COPD, at a stable dose for at least 3 months prior to the screening and randomization visits
- Documentation (including imagery and report) of chest x-ray (CXR) or CT scan performed within 6 months prior to the screening visit, without evidence of significant abnormalities (other than those related to the presence of COPD).
- A cooperative attitude and ability to demonstrate correct use of the pMDI inhalers and eDiary.
Exclusion Criteria:
- Female subjects who are pregnant (as evident by a positive urine hCG or serum β-hCG test) or lactating
-
Subjects using the following medications prior to the screening visit and during the run-in period:
- Systemic/oral/parenteral corticosteroids in the prior 4 weeks
- Use of antibiotics for a lower respiratory tract infection (e.g. pneumonia) or COPD exacerbation in the prior 4 weeks
- Any long-term chronic maintenance use of antibiotic treatment in the prior 4 weeks
- Oral xanthine derivatives (e.g. theophylline) in the prior 7 days
- A moderate or severe COPD exacerbation or a respiratory tract infection (e.g., pneumonia) that has not resolved ≤14 days prior to the screening visit or during the run-in period
- Current treatment with non-cardioselective β-blockers
- Requirement of long term (> 15 hours daily) oxygen therapy
- Known respiratory disorders other than COPD which may impact the efficacy of the study drug according to investigator's judgement.
- Lung transplant surgery or lung volume reduction surgery (subjects with lung volume reduction surgery are excluded if the procedure was performed within 1 year before the Screening visit)
- Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the investigator, would prevent use of anticholinergic agents
- History of hypersensitivity to M3 receptor antagonists, β2 agonists, corticosteroids or any of the excipients contained in any of the study drugs used in the trial which may raise contra-indications or impact the efficacy of the study drug according to the investigator's judgement
- Subject has severe, acute or uncontrolled cardiovascular condition (such as but not limited to unstable ischemic heart disease, NYHA Class IV, left ventricular failure, acute myocardial infarction or unstable angina) in the last 6 months
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An abnormal and clinically significant 12-lead ECG at either the screening or randomization visit. This is characterized as but not limited to any of the following findings:
- Atrial fibrillation (AF) with rapid ventricular response > 120 bpm
- Ventricular tachycardias (sustained, non-sustained [>3 up to 30 sec])
- Evidence of Mobitz Type II second degree or third-degree atrioventricular block
- Prolonged QTcF (>450ms for males, or >470ms for females). This criterion is not applicable for subjects with a pacemaker or permanent AF.
- Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator's judgement
- Unstable or uncontrolled concurrent disease which may impact the efficacy or safety of the study drug or the subject's participation in the study according to investigator's judgment
- Malignancy that has not been in complete remission for at least 1 year or any untreated localized carcinomas
- History of alcohol abuse and/or substance/drug abuse within 12 months prior to the screening visit
- Receipt of any other investigational drug within 1 month or 5 half-lives (whichever is greater) prior to the screening visit or have been previously randomized in this trial, or are currently participating in another clinical trial
- Currently in the acute phase of a pulmonary rehabilitation program within 4 weeks before the screening visit or planning to enroll in the acute phase of such a program during the study. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded
- Mentally or legally incapacitated, or subjects incarcerated as a result of an official or judicial order
- Major surgery in the 3 months prior to the screening visit or have a planned surgery during the trial
- Non-satisfactory compliance with the eDiary (<65% or >135%) during the run-in period
- Subjects requiring the use of spacer device or nebulizer for administration of maintenance COPD therapies.
- Veins unsuitable for repeat venipuncture
- Blood donation or blood loss (≥450mL) in the 4 weeks before randomization
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Sexes Eligible for Study: |
All |
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40 Years and older (Adult, Older Adult)
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No
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Argentina, Bulgaria, Canada, Czechia, Hungary, Mexico, Poland, Puerto Rico, Romania, United States
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Russian Federation, Ukraine
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NCT04320342
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CLI-05993AA3-06 2020-002389-16 ( EudraCT Number )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Chiesi Farmaceutici S.p.A.
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Same as current
|
Chiesi Farmaceutici S.p.A.
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Same as current
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Not Provided
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Principal Investigator: |
Gregory M Feldman, MD |
Vitalink Research - Spartanburg |
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Chiesi Farmaceutici S.p.A.
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April 2024
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