Study on Foster Efficacy Maintenance and Reliever vs Foster Maintenance + Salbutamol Reliever in Asthmatics (MART2)
48-week, Multicentre, Multinational, Randomized, Double-blind, 2-arm Parallel Group, Comparing the Efficacy of FOSTER for Maintenance & Reliever Versus Fixed-dose FOSTER for Maintenance + Salbutamol as Reliever in Asthmatics ≥ 18 Years of Age
Primary objective:
The primary objective of the study was to compare the efficacy of Maintenance and Reliever Therapy (MART) with Foster® 100/6 μg (one inhalation bid) plus additional inhalations as needed, with the standard treatment of Foster® 100/6 μg (one inhalation bid) plus salbutamol 100 μg (Ventolin ®) additional inhalations as needed in not fully controlled asthmatic patients.
Secondary objectives:
The secondary objectives of the study were:
- to evaluate the effect of treatments on lung function parameters and on other clinical outcome measures, and
- to assess the safety and the tolerability of Foster® as MART.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This was a 48-week phase III, double-blind, randomized, 2-arm parallel group study in asthmatic patients (adults of both sexes) not fully controlled under ICS treatment.
The study plan included:
- A pre-screening visit (V0, 3-10 days before V1) to explain the aim of the study, to sign the informed consent form and to prepare patients for V1;
- A screening visit (V1, week -2) to assess inclusion/exclusion criteria followed by a 2-week run-in period when the patients received Foster® 100/6μg, one inhalation twice a day plus salbutamol for reliever medication;
- A randomization visit (V2, week 0) when patients were allocated to one of the two treatment arms:
A) Foster® 100/6 μg one inhalation bid for maintenance plus additional inhalations as needed; B) Foster® 100/6 μg one inhalation bid for maintenance plus salbutamol as needed.
- And subsequent visits taking place at clinics after 4 (V3), after 12 (V4), after 24 (V5), after 36 (V6) and after 48 weeks (V7) of treatment.
The total study duration per participant was 50 weeks, including the 2-week run-in period, 48-week treatment phase.
Salbutamol was used as a rescue medication.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Burgas, Bulgaria
- Chiesi Site No 103
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Pleven, Bulgaria
- Chiesi Site No 107
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Plovdiv, Bulgaria
- Chiesi Site No 105
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Plovdiv, Bulgaria
- Chiesi Site No 111
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Plovdiv, Bulgaria
- Chiesi Site No 115
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Rousse, Bulgaria
- Chiesi Site No 102
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Sofia, Bulgaria
- Chiesi Site No 104
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Sofia, Bulgaria
- Chiesi Site No 108
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Sofia, Bulgaria
- Chiesi Site No 109
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Sofia, Bulgaria
- Chiesi Site No 110
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Sofia, Bulgaria
- Chiesi Site No 113
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Sofia, Bulgaria
- Chiesi Site No 117
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Stara Zagora, Bulgaria
- Chiesi Site No 106
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Troyan Municipality, Bulgaria
- Chiesi Site No 116
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Varna, Bulgaria
- Chiesi Site No 0101
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Veliko Tarnovo, Bulgaria
- Chiesi Site No 112
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Osijek, Croatia
- Chiesi Site No 305
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Rijeka, Croatia
- Chiesi Site No 304
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Zadar, Croatia
- Chiesi Site No 306
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Zagreb, Croatia
- Chiesi Site No 301
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Zagreb, Croatia
- Chiesi Site No 302
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Zagreb, Croatia
- Chiesi Site No 307
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Beroun, Czechia
- Chiesi Site No 201
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Brno, Czechia
- Chiesi Site No 206
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Brno, Czechia
- Chiesi Site No 207
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Prague, Czechia
- Chiesi Site No 202
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Prague, Czechia
- Chiesi Site No 203
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Prague, Czechia
- Chiesi Site No 204
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Prague, Czechia
- Chiesi Site No 205
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Prague, Czechia
- Chiesi Site No 208
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Angoulême, France
- Chiesi Site No 428
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Castelnau-le-Lez, France
- Chiesi Site No 421
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Chauny, France
- Chiesi Site No 434
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Dijon, France
- Chiesi Site No 403
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Hyères, France
- Chiesi Site No 408
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Marmande, France
- Chiesi Site No 424
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Marseille, France
- Chiesi Site No 410
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Marseille, France
- Chiesi Site No 436
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Montpellier, France
- Chiesi Site No 418
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Nice, France
- Chiesi Site No 417
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Nîmes, France
- Chiesi Site No 435
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Ollioules, France
- Chiesi Site No 426
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Paris, France
- Chiesi Site No 401
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Paris, France
- Chiesi Site No 423
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Perpignan, France
- Chiesi Site No 404
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Poitiers, France
- Chiesi Site No 405
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Pézenas, France
- Chiesi Site No 425
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Saint-Etienne, France
- Chiesi Site No 416
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Saint-Girons, France
- Chiesi Site No 420
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Saint-Michel, France
- Chiesi Site No 402
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Saint-Quentin, France
- Chiesi Site No 411
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Soissons, France
- Chiesi Site No 406
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Toulon, France
- Chiesi Site No 422
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Toulon, France
- Chiesi Site No 432
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Verdun, France
- Chiesi Site No 414
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Bochum, Germany
- Chiesi Site No 514
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Bonn, Germany
- Chiesi Site No 520
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Cologne, Germany
- Chiesi Site No 510
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Dortmund, Germany
- Chiesi Site No 502
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Duisburg, Germany
- Chiesi Site No 516
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Düren, Germany
- Chiesi Site No 504
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Frankfurt, Germany
- Chiesi Site No 503
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Frankfurt, Germany
- Chiesi Site No 511
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Hagen, Germany
- Chiesi Site No 506
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Hamburg, Germany
- Chiesi Site No 513
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Koblenz, Germany
- Chiesi Site No 508
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Koblenz, Germany
- Chiesi Site No 509
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Krefeld, Germany
- Chiesi Site No 519
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Ludwigshafen, Germany
- Chiesi Site No 512
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München, Germany
- Chiesi Site No 505
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Neuss, Germany
- Chiesi Site No 515
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Weyhe, Germany
- Chiesi Site No 501
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Witten, Germany
- Chiesi Site No 518
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Benevento, Italy
- Chiesi Site No 606
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Brescia, Italy
- Chiesi Site No 633
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Castrovillari, Italy
- Chiesi Site No 632
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Cittadella, Italy
- Chiesi Site No 612
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Crema, Italy
- Chiesi Site No 607
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Ferrara, Italy
- Chiesi Site No 601
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Foggia, Italy
- Chiesi Site No 610
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Genova, Italy
- Chiesi Site No 604
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Genova, Italy
- Chiesi Site No 605
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Impruneta, Italy
- Chiesi Site No 619
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Messina, Italy
- Chiesi Site No 631
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Milan, Italy
- Chiesi Site No 627
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Milan, Italy
- Chiesi Site No 636
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Modena, Italy
- Chiesi Site No 608
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Montescano, Italy
- Chiesi Site No 611
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Naples, Italy
- Chiesi Site No 635
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Palermo, Italy
- Chiesi Site No 603
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Palermo, Italy
- Chiesi Site No 624
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Palermo, Italy
- Chiesi Site No 630
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Parma, Italy
- Chiesi Site No 615
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Perugia, Italy
- Chiesi Site No 628
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Pietra Ligure, Italy
- Chiesi Site No 613
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Pisa, Italy
- Chiesi Site No 602
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Reggio Calabria, Italy
- Chiesi Site No 625
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Roma, Italy
- Chiesi Site No 618
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Roma, Italy
- Chiesi Site No 626
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Sesto San Giovanni, Italy
- Chiesi Site No 609 "Sesto San Giovanni (MI)"
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Vicenza, Italy
- Chiesi Site No 614
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Bialystok, Poland
- Chiesi Site No 720
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Bialystok, Poland
- Chiesi Site No 724
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Bialystok, Poland
- Chiesi Site No 741
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Bielsko-Biala, Poland
- Chiesi Site No 729
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Gdansk, Poland
- Chiesi Site No 709
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Gdansk, Poland
- Chiesi Site No 719
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Gdynia, Poland
- Chiesi Site No 738
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Giżycko, Poland
- Chiesi Site No 707
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Iława, Poland
- Chiesi Site No 704
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Katowice, Poland
- Chiesi Site No 705
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Katowice, Poland
- Chiesi Site No 739
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Krakow, Poland
- Chiesi Site No 711
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Krakow, Poland
- Chiesi Site No 721
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Krakow, Poland
- Chiesi Site No 722
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Krakow, Poland
- Chiesi Site No 727
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Krakow, Poland
- Chiesi Site No 728
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Legionowo, Poland
- Chiesi Site No 716
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Lodz, Poland
- Chiesi Site No 701
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Lodz, Poland
- Chiesi Site No 702
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Lodz, Poland
- Chiesi Site No 703
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Lodz, Poland
- Chiesi Site No 713
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Lodz, Poland
- Chiesi Site No 723
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Lodz, Poland
- Chiesi Site No 726
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Lodz, Poland
- Chiesi Site No 736
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Lodz, Poland
- Chiesi Site No 740
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Lubin, Poland
- Chiesi Site No 715
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Lublin, Poland
- Chiesi Site No 718
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Lublin, Poland
- Chiesi Site No 730
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Ostróda, Poland
- Chiesi Site No 735
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Proszowice, Poland
- Chiesi Site No 725
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Rzeszów, Poland
- Chiesi Site No 737
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Starachowice, Poland
- Chiesi Site No 710
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Strzelce Opolskie, Poland
- Chiesi Site No 708
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Sucha Beskidzka, Poland
- Chiesi Site No 706
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Warsaw, Poland
- Chiesi Site No 742
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Wilkowice, Poland
- Chiesi Site No 732
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Wroclaw, Poland
- Chiesi Site No 712
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Wroclaw, Poland
- Chiesi Site No 733
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Zabrze, Poland
- Chiesi Site No 714
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Łomża, Poland
- Chiesi Site No 717
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Brasov, Romania
- Chiesi Site No 805
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Bucharest, Romania
- Chiesi Site No 801
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Bucharest, Romania
- Chiesi Site No 807
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Bucharest, Romania
- Chiesi Site No 808
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Cluj-Napoca, Romania
- Chiesi Site No 810
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Constanța, Romania
- Chiesi Site No 806
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Iași, Romania
- Chiesi Site No 804
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Târgu Mureş, Romania
- Chiesi Site No 811
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Moscow, Russia
- Chiesi Site No 901
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Moscow, Russia
- Chiesi Site No 902
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Moscow, Russia
- Chiesi Site No 903
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Moscow, Russia
- Chiesi Site No 904
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Moscow, Russia
- Chiesi Site No 905
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Moscow, Russia
- Chiesi Site No 906
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Moscow, Russia
- Chiesi Site No 907
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Moscow, Russia
- Chiesi Site No 916
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Moscow, Russia
- Chiesi Site No 917
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Moscow, Russia
- Chiesi Site No 918
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Ryazan, Russia
- Chiesi Site No 915
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Saratov, Russia
- Chiesi Site No 913
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Saratov, Russia
- Chiesi Site No 914
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Yaroslavl, Russia
- Chiesi Site No 908
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Yaroslavl, Russia
- Chiesi Site No 909
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Yaroslavl, Russia
- Chiesi Site No 910
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Yaroslavl, Russia
- Chiesi Site No 911
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Yaroslavl, Russia
- Chiesi Site No 912
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Belgrade, Serbia
- Chiesi Site No 1001
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Belgrade, Serbia
- Chiesi Site No 1003
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Kamenitz, Serbia
- Chiesi Site No 1002
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Kragujevac, Serbia
- Chiesi Site No 1004
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Niš, Serbia
- Chiesi Site No 1005
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Badalona, Spain
- Chiesi Site No 1101
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Lleida, Spain
- Chiesi Site No 1102
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Terrassa, Spain
- Chiesi Site No 1105
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Zaragoza, Spain
- Chiesi Site No 1106
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Adana, Turkey (Türkiye)
- Chiesi Site No 1216
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Ankara, Turkey (Türkiye)
- Chiesi Site No 1213
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Aydin, Turkey (Türkiye)
- Chiesi Site No 1204
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Gaziantep, Turkey (Türkiye)
- Chiesi Site No 1203
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Istanbul, Turkey (Türkiye)
- Chiesi Site No 1208
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Istanbul, Turkey (Türkiye)
- Chiesi Site No 1214
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Istanbul, Turkey (Türkiye)
- Chiesi Site No 1215
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Izmir, Turkey (Türkiye)
- Chiesi Site No 1217
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Kayseri, Turkey (Türkiye)
- Chiesi Site No 1201
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Kirikkale, Turkey (Türkiye)
- Chiesi Site No 1202
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Konya, Turkey (Türkiye)
- Chiesi Site No 1207
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Malatya, Turkey (Türkiye)
- Chiesi Site No 1211
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Manisa, Turkey (Türkiye)
- Chiesi Site No 1210
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Tokat Province, Turkey (Türkiye)
- Chiesi Site No 1205
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Trabzon, Turkey (Türkiye)
- Chiesi Site No 1209
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Donetsk, Ukraine
- Chiesi Site No 1410
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Kharkiv, Ukraine
- Chiesi Site No 1401
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Kharkiv, Ukraine
- Chiesi Site No 1406
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Kharkiv, Ukraine
- Chiesi Site No 1407
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Kharkiv, Ukraine
- Chiesi Site No 1408
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Kharkiv, Ukraine
- Chiesi Site No 1417
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Kharkiv, Ukraine
- Chiesi Site No 1418
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Kiev, Ukraine
- Chiesi Site No 1402
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Kiev, Ukraine
- Chiesi Site No 1403
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Luhansk, Ukraine
- Chiesi Site No 1405
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Odesa, Ukraine
- Chiesi Site No 1412
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Simferopol, Ukraine
- Chiesi Site No 1411
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Glasgow, United Kingdom
- Chiesi Site No 1301
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Hereford, United Kingdom
- Chiesi Site No 1306
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Newcastle, United Kingdom
- Chiesi Site No 1305
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Written signed and dated informed consent obtained from patient;
- Male or female patients aged ≥ 18 years;
- Clinical diagnosis of asthma for ≥ 6 months;
- A positive reversibility test, defined as an increase of at least 12% and at least 200 mL from pre-dose in FEV1 30 minutes following 4 puffs (4 × 100 μg) of inhaled salbutamol pMDI. If this could not be achieved, a documented reversibility test to salbutamol within the last 6 months was acceptable for eligibility;
- Patients who experienced at least one severe exacerbation in the 12 months before entry (but not in the last month), defined as deterioration in asthma resulting in hospitalization or emergency room treatment due to asthma worsening, or the need for systemic steroids for at least 3 days because of asthma;
Using inhaled corticosteroids (ICS) in monotherapy or using ICS in a fixed or free combination with long acting β2 agonists (LABA) at a constant dose (changes in doses for less than seven days were accepted) for two months before V1.
- If patients were under ICS only, the daily dose had to be ≥ non-extrafine 1000 μg BDP or equivalent.
- If patients were under ICS + LABA, the ICS daily dose had to be ≥ non-extrafine 500 μg BDP or equivalent. LABA were to be stopped at least 24 hours before V1.
Not fully controlled asthmatics (which means partly controlled or/and uncontrolled patients according to GINA guidelines 2007) (apart from asthma exacerbation criteria) in the last month before V1.
Asthma control was assessed in terms of:
- Daytime symptoms (more than twice a week);
- Limitation of activities (any);
- Nocturnal symptoms/awakening (any);
- Need for rescue (more than twice a week);
- Forced expiratory volume in the first second (FEV1) < 80% predicted (or personal best, if known) on any day.
Partly controlled patients were those with at least one of the above mentioned symptoms/signs in any week of the last month before V1.
Uncontrolled patients were those with 3 or more features of partly controlled asthma present in any week of the last month before V1.
- FEV1 ≥ 60% of predicted for the patient normal value;
- Non smokers or ex-smokers (defined as those who have stopped smoking for more than one year and with a smoking history of less than 10 pack/years); Pack/year: number of cigarettes smoked per day multiplied by the number of years of smoking/20.
- A co-operative attitude and ability to be trained to correctly use the pMDI;
- Subjects who were willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Not fully controlled asthma (defined according to criterion No. 7) in the last week of the run-in was to be confirmed at Visit 2.
Exclusion Criteria:
Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotrophin laboratory test (> 5 mIU/mL). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precluded intercourse with a male partner and women whose partners had been sterilized by vasectomy or other means, unless they met the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or were using one or more of the following acceptable methods of contraception:
- Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy);
- Hormonal contraception (implantable, patch, oral);
- Double-barrier methods (any double combination of: IUD, male or female condom, diaphragm, sponge, cervical cap).
Acceptable methods of contraception could include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensured compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal were not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation;
- Body Mass Index (BMI) > 34 kg/m2;
- Patients with lower respiratory tract infections affecting the patient's asthma within 30 days of the screening visit;
- Use of systemic steroids in the last month;
- Patients with other lung diseases such as (but not limited to) COPD, cystic fibrosis, interstitial lung diseases or any other clinically or functionally significant lung disorder;
- Patients who had an uncontrolled respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that could, in the judgment of the investigator, represent for the patients an undue risk or that could compromise the results or interpretation of the study;
- History or current evidence of uncontrolled heart failure, clinically relevant coronary artery disease, recent myocardial infarction, severe hypertension, uncontrolled cardiac arrhythmias;
- Cancer or any other chronic disease with poor prognosis (less than 2 years) and /or affecting patient status;
- Clinically relevant laboratory abnormalities such as (but not limited to) hypokaliemia (<3.5 mEq/L), that could compromise patient's safety or compliance, interfere with evaluation, or preclude completion of the study, in the judgment of the investigator. Patients with uncontrolled diabetes, including patients with a history of serum glucose levels consistently out of the normal range (> 140 mg/dl) or HbA1c > 8.0%, were to be excluded from the study;
- Patients who had an abnormal QTcF interval value in the screening visit ECG test (i.e., > 450 msec in males or > 470 msec in females);
- Intolerance or contra-indication to treatment with β2-agonists and/or ICS or allergy to any component of the study treatments;
- Patients treated with slow-release corticosteroids in the 3 months prior to screening visit;
- Patients unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study treatments;
- Patients being treated with anti-IgE antibodies;
- Patients treated with LABA or ICS/LABA fixed combination in the 24 hours before visit 1;
- Patients having received an investigational drug within 2 months before the screening visit;
- Inability to comply to study procedures or to study treatment intake;
- Inability to carry out a valid spirometry;
- Severe asthma exacerbation in the last month before screening visit;
- Severe asthma exacerbation during the run-in period.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Foster (Treatment A)
Participants received one inhalation of Foster (beclomethasone dipropionate 100 µg plus formoterol 6 µg/unit dose) administered via a pMDI, BID, as maintenance therapy and additional inhalations of Foster (beclomethasone dipropionate 100 µg plus formoterol 6 µg/unit dose) as needed in response to symptoms as reliever therapy.
A maximum of 6 inhalations per day was allowed as reliever therapy.
To ensure blinding, participants received inhalations of placebo matching Ventolin as reliever therapy.
Participants received treatment for a duration of 48 weeks.
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Administered via a pressurized metered-dose inhaler
Other Names:
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Active Comparator: Foster + Ventolin (Treatment B)
Participants received one inhalation of Foster (beclomethasone dipropionate 100 µg plus formoterol 6 µg/unit dose) administered via a pMDI, BID, as maintenance therapy and additional inhalations of Ventolin (Salbutamol, 100 μg per metered dose) as needed in response to symptoms as reliever therapy.
A maximum of 6 inhalations per day was allowed as reliever therapy.
To ensure blinding, participants received inhalations of placebo matching Foster as reliever therapy.
Participants received treatment for a duration of 48 weeks.
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Administered via a pressurized metered-dose inhaler
Other Names:
Administered via a pressurized metered-dose inhaler
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Time to First Severe Asthma Exacerbation
Time Frame: From First IMP dose to week 48 (EOT)
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A severe asthma exacerbation was defined as asthma worsening resulting in hospitalization or emergency room treatment due to asthma worsening, or the need for systemic steroids for ≥ 3 days because of asthma. First severe asthma exacerbation occurred after the first dose of randomised study drug and within end of study was considered for the analysis. Patients without a severe asthma exacerbation or withdrawn before having it, are considered as 'censored' at the last day in the study or at the time of the withdrawal. Since the median time (50th percentile) and the other key percentiles (25th and 75th) were not reached, the median time of first exacerbation is not available (N.A.). So, to provide meaningful information, the cumulative number of patients who experienced a severe exacerbation at the end of each time period was reported separately. |
From First IMP dose to week 48 (EOT)
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Cumulative Number of Patients With Severe Asthma Exacerbation by Inter-visit (Measured in Weeks)
Time Frame: From First dose to end of each interval: 0-4, 4-12, 12-24, 24-36, 36-48 weeks
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A severe asthma exacerbation was defined as asthma worsening resulting in hospitalization or emergency room treatment due to asthma worsening, or the need for systemic steroids for ≥ 3 days because of asthma. First severe asthma exacerbation occurred after the first dose of randomised study drug and within end of study was considered for the analysis. Patients without a severe asthma exacerbation or withdrawn before having it, are considered as 'censored' at the last day in the study or at the time of the withdrawal. As already anticipated in the primary endpoint, since the median time (50th percentile) and the other key percentiles (25th and 75th) were not reached, and the median time of first exacerbation is not available (N.A.), to provide meaningful information, the cumulative number of patients who experienced a severe exacerbation at the end of each time period is here reported. |
From First dose to end of each interval: 0-4, 4-12, 12-24, 24-36, 36-48 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Number of Severe Asthma Exacerbations Per 100 Patients Per Year
Time Frame: First dose to end of the study (Up to 48 Weeks)
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A severe asthma exacerbation was defined as asthma worsening, resulting in hospitalization or emergency room treatment due to asthma worsening, or the need for systemic steroids for ≥ 3 days. As per the outcome measure title, the total number of severe exacerbations (this outcome), of hospitalisations/emergency room treatment, of systemic corticosteroids use (other outcomes) is expressed as rate (events per 100 patients per year) and compared between arms. Please note that in case of two close severe asthma exacerbations (start date of a severe asthma exacerbation is less than 10 days from the stop date of the previous severe asthma exacerbation), only the first was counted for the analysis. |
First dose to end of the study (Up to 48 Weeks)
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Number of Systemic Corticosteroids Courses to Treat Asthma Per 100 Patients Per Year
Time Frame: First dose to end of the study (Up to 48 Weeks)
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Systemic corticosteroids courses to treat asthma started at or after the first dose of randomised study drug and with at least one day from the stop date of a systemic corticosteroids course and the start date of the following one have been considered for analysis.
As per the outcome measure title, the total number of severe exacerbations (other outcome), of hospitalisations/emergency room treatment (other outcome), of systemic corticosteroids use (this outcome) is expressed as rate (events per 100 patients per year) and compared between arms.
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First dose to end of the study (Up to 48 Weeks)
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Number of Hospitalisation/Emergency Room Treatments Due to Asthma Per 100 Patients Per Year
Time Frame: From first dose to end of the study (Up to Week 48)
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Hospitalization or emergency room treatment due to asthma started at or after the first dose of randomised study drug was be considered for the analysis. As per the outcome measure title, the total number of severe exacerbations (another outcome), of hospitalisations/emergency room treatment (this outcome), of systemic corticosteroids use (other outcomes) is expressed as rate (events per 100 patients per year) and compared between arms. |
From first dose to end of the study (Up to Week 48)
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Change From Baseline in Asthma Control Questionnaire (ACQ) Score to Each Visit
Time Frame: Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6), Week 48 (V7)
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The Asthma Control Questionnaire is a tool used to asses how well a participant asthma is controlled and consists of seven questions scored. On average/in general, during the past week 0 (no impairment), 6 (maximum impairment for symptoms).
The ACQ total score has been calculated as the mean of the seven question scores ranging from 0 (totally controlled) and 6 (severely uncontrolled). Higher scores indicate the worse outcomes. Adjusted means were reported. |
Week 4 (V3), Week 12 (V4), Week 24 (V5), Week 36 (V6), Week 48 (V7)
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Number of Mild Asthma Exacerbations Per 100 Patients / Year
Time Frame: From first dose through end of the study (Up to Week 48)
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A mild asthma exacerbation was defined as two consecutive mild asthma exacerbation days satisfying the same criterion. In case periods satisfying different criteria overlapping, only one mild asthma exacerbation was considered. In case of two close mild asthma exacerbations (start date of a mild asthma exacerbation is less than 7 days from the stop date of the previous mild asthma exacerbation), only the first was counted for the analysis. Mild asthma exacerbations occurred at or after the first dose of randomised study drug and within end of study is considered for the analysis. As per the outcome measure title, the total number of mild asthma exacerbations is expressed as rate (events per 100 patients per year) and compared between arms. |
From first dose through end of the study (Up to Week 48)
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Number of Mild Asthma Exacerbations: Number of Total Events
Time Frame: From first dose through end of the study (Up to Week 48)
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A mild asthma exacerbation was defined as two consecutive mild asthma exacerbation days satisfying the same criterion. In case periods satisfying different criteria overlapping, only one mild asthma exacerbation was considered. In case of two close mild asthma exacerbations (start date of a mild asthma exacerbation is less than 7 days from the stop date of the previous mild asthma exacerbation), only the first was counted for the analysis. Total number of mild asthma exacerbation events were reported. Mild asthma exacerbations occurred at or after the first dose of randomised study drug and within end of study is considered for the analysis. . |
From first dose through end of the study (Up to Week 48)
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Time to First Mild Asthma Exacerbation
Time Frame: From first dose to end of the study (Up to Week 48)
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A "mild asthma exacerbation" was defined as two consecutive mild asthma exacerbation days satisfying the same criterion. In case periods satisfying different criteria overlapping, only 1 mild exacerbation was considered. In case of two close mild exacerbations (start date of a mild exacerbation is less than 7 days from the stop date of the previous mild exacerbation), only the first was counted for the analysis. First mild exacerbation occurred after the first dose of randomised study drug and within end of study is considered for the analysis. In patient with at least one mild exacerbation, the time to first mild exacerbation was calculated as the time in days between the first dose of randomised study drug (derived) and the time at which the first mild exacerbation occurs (date of the first day of the first mild exacerbation). Time to first mild asthma exacerbation (days) = (date of first day of first mild exacerbation - date of first dose of randomised study drug (derived)) +1 |
From first dose to end of the study (Up to Week 48)
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Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF) to Each Visit
Time Frame: Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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PEF is measured twice a day (morning and evening) with Spirotel, a portable electronic peak flow meter.
PEF measurement recorded in the morning of the day of each clinic visit was considered as data of the period before clinic visit.
During each measurement session (morning or evening before the intake of the study medication) the participant performed 3 blows and only the best PEF parameter was saved into the Spirotel memory.
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Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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Change From Baseline in Daily PEF Variability to Each Visit
Time Frame: Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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PEF is measured twice a day (morning and evening) with Spirotel. PEF measurement recorded in the morning of the day of each clinic visit was considered as data of the period before clinic visit. During each measurement session (morning or evening before the intake of the study medication) the participant will perform 3 blows and only the best PEF parameter will be saved into the Spirotel memory. The variability of PEF of a day will be calculated using the Best PEF morning and the Best PEF evening recorded in the same day. Variability of PEF is measured daily with Spirotel using the following formula: Best PEF evening - Best PEF morning/Best PEF evening + Best PEF morning/2 X 100 |
Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Each Visit
Time Frame: Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second.
FEV1 was measured using spirometry, conducted at baseline and all clinical visits.
An increase in FEV1 reflects improved airway patency, while a decrease suggests worsening obstruction.
Higher FEV1 values indicate better lung function.
Adjusted means were reported.
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Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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Change From Baseline in Pre-Dose Forced Expiratory Flow Between 25% and 75% of Vital Capacity (FEF25-75%) at Each Visit
Time Frame: Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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FEF is a lung function test and is measured using the spirometery.
The FEF25%-75% is the forced expiratory flow from 25% to 75% of FVC.
FEF25%-75% measurement is conducted at baseline and all clinical visits.
An increase in FEF25%-75% reflects improved airway patency, while a decrease suggests worsening obstruction.
Higher FEF25%-75% values indicate better lung function.
Adjusted means were reported.
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Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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Change From Baseline in Total Asthma Symptom Scores Measured Daily by Each Visit
Time Frame: Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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The asthma symptoms are: cough, wheeze, chest tightness and breathlessness. Each morning and evening asthma symptoms are to be scored, as respectively occurred during the night and during the day, as follows: Night-time asthma symptom score: 0 = No symptom, 1 = Mild: symptoms not causing awakening, 2 = Moderate: discomfort enough to cause awakening, 3 = Severe: causing awakening for most of the night / do not allow to sleep at all Day-time asthma symptom score: 0 = No symptom, 1 = Mild: aware of symptoms which can be easily tolerated, 2 = Moderate: discomfort enough to cause interference with daily activity, 3 = Severe: incapacitating with inability to work / take part in usual activity Total asthma symptoms score was calculated as the sum of the day-time and the night-time asthma symptoms score recorded on the following day and score ranges from 0 to 6, higher score indicates worse symptoms. |
Baseline, Weeks 4 (V3), 12 (V4), 24 (V5), 36 (V6), 48 (V7)
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Number of Inhalations of Reliever Medication Per Day by Each Two-Week Period
Time Frame: Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18,19-20,21-22, 23-24, 25-26, 27-28, 29-30, 31-32, 33-34, 35-36, 37-38, 39-40, 41-42, 43-44, 45-46, 47-48
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The daily use of reliever medication was calculated as sum of the number of puffs taken during the day and the number of puffs taken during the night recorded on the following day.
In case one session in a day is missing, only the available session (evening or morning) was considered for the daily use of reliever medication.
A minimum of seven evaluable measurements are required in each two-week treatment period and during the two-weeks of the run-in period (baseline).
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Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18,19-20,21-22, 23-24, 25-26, 27-28, 29-30, 31-32, 33-34, 35-36, 37-38, 39-40, 41-42, 43-44, 45-46, 47-48
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Percentage of Asthma Symptom-free Days by Each Two-Week Period
Time Frame: Week 3-4, 11-12, 23-24, 35-36 and 47-48
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Asthma symptom-free days are days with the total asthma symptom score equal to zero. Percentage of asthma symptom-free days will be calculated in each two-week period using the following formula: % of asthma symptoms- free days = Number o f asthma symptoms- free days in that two - week period/Number o f days with data recorded for asthma symptom scores in that two - week period X 100. |
Week 3-4, 11-12, 23-24, 35-36 and 47-48
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Percentage of Reliever-Medication-Free Days by Each Two-Week Period
Time Frame: Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18,19-20,21-22, 23-24, 25-26, 27-28, 29-30, 31-32, 33-34, 35-36, 37-38, 39-40, 41-42, 43-44, 45-46, 47-48
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A day without reliever medication is a day in which the number of puffs of reliever medication taken in the 24 hours is zero. A day will be considered as missing if both measurements (evening and morning) are missing. A day will be considered as "not-free" if one session is recorded and the other is missing. Percentage of reliever medication-free days will be calculated in each two-week period using the following formula: % of reliever medication-free days = Number of reliever medication-free days in that two -week period/Number of days with data recorded for reliever medication in that two -week period X 100 |
Weeks 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, 13-14, 15-16, 17-18,19-20,21-22, 23-24, 25-26, 27-28, 29-30, 31-32, 33-34, 35-36, 37-38, 39-40, 41-42, 43-44, 45-46, 47-48
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Percentage of Asthma Control Days by Each Two-week Period Before Clinic Visits
Time Frame: Week 3-4, 11-12, 23-24, 35-36 and 47-48
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Asthma control day is a day with total asthma symptom score equal to zero and without use of reliever medication. A day will be considered as missing if both measurements (evening and morning) are missing. A day will be considered as "not control" if one session is recorded and the other is missing. Percentage of asthma control days will be calculated in each two-week period using the following formula: % of asthma control days = Number of asthma control days in that two -week period/Number of days with data recorded for asthma symptom scores and reliever medication in that two-week period X100 |
Week 3-4, 11-12, 23-24, 35-36 and 47-48
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Number of Participants With Treatment Emergent Adverse Events
Time Frame: From first dose of study drug until end of the study (up to 48 weeks)
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AE=An untoward medical occurrence after exposure to a medicine, which is not necessarily caused by that medicine. Serious AE= An adverse event that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect. ADR=A response to a medicinal product which is harmful and unintended. Response in this context means that a causal relationship between the medicinal product and an adverse event is at least a reasonable possibility Serious ADR=An adverse reaction that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect. Severe AE= "Severe" refers to the intensity of an AE; the event itself may be of relatively minor medical significance but intense. |
From first dose of study drug until end of the study (up to 48 weeks)
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Number of Patients Who Required > 6 Rescue Inhalations Per Day for at Least Two Consecutive Days During During Treatment Period
Time Frame: From first dose of study drug until end of the study (up to 48 weeks)
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Use of reliever medication was derived from the data of SpirotelTM.
The event "more than six reliever medications per day for two consecutive days" is defined as at least two consecutive days with more than six puffs of reliever medication in the day.
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From first dose of study drug until end of the study (up to 48 weeks)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Alberto Papi, Professor, Università degli Studi di Ferrara
Publications and helpful links
General Publications
- Papi A, Corradi M, Pigeon-Francisco C, Baronio R, Siergiejko Z, Petruzzelli S, Fabbri LM, Rabe KF. Beclometasone-formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir Med. 2013 Mar;1(1):23-31. doi: 10.1016/S2213-2600(13)70012-2. Epub 2013 Mar 4.
- Morjaria JB, Rigby AS, Morice AH. Symptoms and exacerbations in asthma: an apparent paradox? Ther Adv Chronic Dis. 2019 Oct 24;10:2040622319884387. doi: 10.1177/2040622319884387. eCollection 2019.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity, Immediate
- Hypersensitivity
- Asthma
- Organic Chemicals
- Therapeutics
- Polycyclic Compounds
- Amines
- Pregnadienes
- Pregnanes
- Steroids
- Fused-Ring Compounds
- Patient Care
- Health Services
- Health Care Facilities Workforce and Services
- Community Health Services
- Alcohols
- Pregnadienetriols
- Amino Alcohols
- Ethanolamines
- Phenethylamines
- Ethylamines
- Steroids, Chlorinated
- Formoterol Fumarate
- Albuterol
- Beclomethasone
- Foster Home Care
Other Study ID Numbers
- CCD-0804-PR-0034
- 2008-004671-22 (EudraCT Number)
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