Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Fixed Combinations of Long-acting β2-agonists (LABA) and Inhaled Glucocorticosteroid (ICS)

NCT01329029 | Completed Phase 4 Results

• 3 other identifiers: RO-2455-404-RD2010-019685-87U1111-1141-7422
• Study Type: interventional
• Target: 1,945
• Locations: 20 countries
• Sites: 176

Brief Summary

The objective of the REACT trial is to investigate the effect of roflumilast 500 μg tablets once daily versus placebo on exacerbation rate and pulmonary function in COPD patients who are concomitantly treated with a fixed combination of long-acting β2-agonists (LABA) and inhaled glucocorticosteroids (ICS). In addition, data on safety and tolerability of roflumilast will be obtained. An additional objective is to further characterize the population pharmacokinetic profile of roflumilast and roflumilast N oxide and to further characterize their pharmacokinetics/pharmacodynamics (PK/PD) relationship in terms of efficacy and relevant safety aspects. Patients to be included are required to have severe COPD associated with chronic bronchitis and a history of frequent exacerbations and must be concomitantly treated with a fixed combination of LABA and ICS. Two parallel treatment arms (roflumilast 500 μg once daily and placebo) are included.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Roflumilast; Daxas

Outcome Measures

Primary Outcomes (1)

• Rate of Moderate or Severe COPD Exacerbations Per Patient Per Year

  A COPD exacerbation is an event in the natural course of the disease characterized by a worsening in the patient's baseline dyspnoea, cough, and/or sputum production beyond day to day variability sufficient to warrant a change in management. COPD exacerbations were categorized as follows: Severe=Requiring hospitalization and/or leading to death; Moderate=Requiring oral or parenteral glucocorticosteroid therapy. The defined number of days a patient was in the trial was divided by 365.25, in order to express the duration as a fraction of 1 year.

  52 weeks

Secondary Outcomes (32)

• Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in the First Second (FEV1)

  Baseline and Week 52

• Rate of Severe COPD Exacerbations Per Patient Per Year

  52 weeks

• Rate of COPD Exacerbations Per Patient Per Year All Categories

  52 weeks

• Percentage of Participants Experiencing at Least 1 COPD Exacerbation

  52 weeks

• Time to First COPD Exacerbation All Categories

  52 Weeks

Study Arms (2)

Roflumilast

ACTIVE COMPARATOR

concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid

Drug: Roflumilast

Placebo

PLACEBO COMPARATOR

concomitant medication: fixed combination of long-acting β2-agonist and inhaled glucocorticosteroid

Drug: Placebo

Interventions

Roflumilast DRUG

500 µg, once daily

Roflumilast

Placebo DRUG

once daily

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Giving written informed consent
• History of COPD (according to GOLD 2009) for at least 12 months prior to baseline Visit V0 associated with chronic productive cough for 3 months in each of the 2 years prior to baseline visit (with other causes of productive cough excluded)
• Age ≥ 40 years
• Forced expiratory volume after one second (FEV1)/forced vital capacity (FVC) ratio (post-bronchodilator) \< 70%
• FEV1 (post-bronchodilator) ≤ 50% of predicted
• At least two documented moderate or severe COPD exacerbations within one year prior to baseline visit
• Patients must be pre-treated with LABA and ICS for at least 12 months before baseline Visit V0. Up to 3 months before baseline Visit V0 free or fixed combinations of LABA and ICS are allowed, including changes in dose, active substances, and brands. In the last 3 months before baseline Visit V0 patients must be pre-treated with fixed combinations of LABA and ICS at a constant dose (maximum approved dosage strength of the combination).
• Former smoker (defined as smoking cessation at least one year ago) or current smoker both with a smoking history of at least 20 pack years

You may not qualify if:

• Exacerbations not resolved at first baseline visit
• Diagnosis of asthma and/or other relevant lung disease
• Known alpha-1-antitrypsin deficiency

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (180)

Nycomed Investigational Site

Box Hill, 3128, Australia

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Clayton, 3168, Australia

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Concord, 2139, Australia

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Daws Park, 5041, Australia

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Frankston, 3199, Australia

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Heidelberg, 3084, Australia

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Parkville, 3050, Australia

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Toorak Gardens, 5065, Australia

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Feldbach, 8330, Austria

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Graz, 8036, Austria

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Salzburg, 5020, Austria

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Vienna, 1140, Austria

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Brussels, 1000, Belgium

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Brussels, 1200, Belgium

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Halen, 3545, Belgium

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Liège, 4000, Belgium

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Malmedy, 4960, Belgium

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Belo Horizonte, Brazil

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Botucatu, Brazil

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Florianópolis, Brazil

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Goiânia, Brazil

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Porto Alegre, Brazil

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Vitória, Brazil

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Hamilton, L8N 4A6, Canada

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Kingston, K7L 2V7, Canada

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Lachine, H8S 2E4, Canada

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Niagara Falls, L2G 1J4, Canada

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Richmond Hill, L4C 2N9, Canada

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Toronto, M5T 3A9, Canada

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Toronto, M6H 3M2, Canada

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Winnepeg, R2K 3S8, Canada

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Hellerup, 2900, Denmark

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Hillerød, 3400, Denmark

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Hvidovre, 2650, Denmark

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København NV, 2400, Denmark

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Férolles-Attilly, 77150, France

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Nîmes, 30900, France

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Poitiers, 86021, France

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Saint-Laurent-du-Var, 06700, France

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Strasbourg, 67091, France

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Berlin, 10367, Germany

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Berlin, 10969, Germany

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Berlin, 12203, Germany

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Fürth, 90766, Germany

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Großhansdorf, 22927, Germany

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Hanover, 30167, Germany

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Homburg, 66421, Germany

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Koblenz, 56068, Germany

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Marburg, 35043, Germany

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Rüdersdorf, 15562, Germany

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Alexandroupoli, 68100, Greece

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Athens, 10676, Greece

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Athens, 11527, Greece

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Heraklion, Crete, 71110, Greece

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Kavala, 65201, Greece

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Larissa, 41100, Greece

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Marousi, 15126, Greece

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Thessaloniki, 57010, Greece

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Balassagyarmat, 2660, Hungary

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Budapest, 1125, Hungary

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Cegléd, 2700, Hungary

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Csorna, 9300, Hungary

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Deszk, 6772, Hungary

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Érd, Hungary

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Miskolc, 3526, Hungary

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Nyíregyháza, 4400, Hungary

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Pécs, 7623, Hungary

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Siófok, 8600, Hungary

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Sopron, 9400, Hungary

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Szombathely, 9700, Hungary

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Törökbálint, 2045, Hungary

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Ashkelon, 78278, Israel

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Beersheba, 84101, Israel

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Haifa, 31096, Israel

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Haifa, 34362, Israel

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Holon, 58100, Israel

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Jerusalem, 91031, Israel

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Jerusalm, 91120, Israel

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Kfar Saba, 44281, Israel

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Petah Tikva, 49100, Israel

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Rehovot, 76100, Israel

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Tel Aviv, 64239, Israel

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Tel Aviv, 67891, Israel

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Tel Litwinsky, 52621, Israel

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Ferrara, 44011, Italy

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Genova, 16132, Italy

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Milan, 20122, Italy

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Milan, 20138, Italy

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Modena, 41100, Italy

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Monza, 20052, Italy

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Pordenone, 33170, Italy

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Roma, 00133, Italy

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's-Hertogenbosch, 5200 ME, Netherlands

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Amersfoort, 3800 BM, Netherlands

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Arnhem, 6815 AD, Netherlands

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Enschede, 7500 KA, Netherlands

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Heerlen, 6419 PC, Netherlands

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Hoorn, 1624 NP, Netherlands

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Bialystok, 15-540, Poland

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Bydgoszcz, 85-681, Poland

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Gliwice, Poland

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Katowice, 40-753, Poland

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Lodz, 90-153, Poland

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Lodz, 91-849, Poland

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Lodz, 94-010, Poland

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Lublin, 20-718, Poland

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Oleśnica, Poland

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Ostrów Wielkopolski, 63-400, Poland

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Tarnów, 33-100, Poland

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Warsaw, Poland

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Wroclaw, 50-127, Poland

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Wroclaw, 53-301, Poland

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Zawadzkie, 47-120, Poland

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Chelyabinsk, 454021, Russia

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Kazan', 420029, Russia

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Kemerovo, 650002, Russia

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Moscow, 105077, Russia

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Moscow, 117485, Russia

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Moscow, 117574, Russia

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Moscow, 125206, Russia

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Nizhny Novgorod, 603011, Russia

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Novosibirsk, 630087, Russia

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Novosibirsk, 630091, Russia

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Saint Petersburg, 196084, Russia

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Saint Petersburg, 197089, Russia

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Saint Petersburg, 197706, Russia

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Samara, Russia

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Saratov, 410012, Russia

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Smolensk, 214006, Russia

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Volgograd, 400001, Russia

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Vsevolozhsk, 188640, Russia

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Yaroslavl, 150010, Russia

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Banská Bystrica, 975 17, Slovakia

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Bardejov, 085 01, Slovakia

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Bratislava, 821 06, Slovakia

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Bratislava, 826 06, Slovakia

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Košice, 040 01, Slovakia

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Martin, 036 01, Slovakia

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Nitra, 950 01, Slovakia

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Nové Zámky, 940 34, Slovakia

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Spišská Nová Ves, 052 01, Slovakia

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Auckland Park, Johannesburg Gauteng, 2006, South Africa

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Benoni Gauteng, 1500, South Africa

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Bloemfontein Free State, 9300, South Africa

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Cape Town Western Cape, 7764, South Africa

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Durban Kwazulu-Natal, 4092, South Africa

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Johannesburg, 2193, South Africa

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Morningside, Johannesburg Gauteng, 2057, South Africa

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Thabazimbi Limpopo, 0380, South Africa

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Umkomaas Kwazulu-Natal, 4170, South Africa

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Witbank Mpumalanga, 1035, South Africa

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Anyang, 431-070, South Korea

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Cheongju-si, 361-711, South Korea

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Daegu, South Korea

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

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Seoul, 152-703, South Korea

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Wŏnju, 220-701, South Korea

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Barcelona, 08022, Spain

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Guadalajara, 19002, Spain

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Madrid, 28007, Spain

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Pozuelo de Alarcón, 28223, Spain

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Santander, 39008, Spain

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Terrassa, 08221, Spain

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Valencia, 46015, Spain

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Ankara, 06590, Turkey (Türkiye)

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Çanakkale, 17020, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Kocaeli, 41380, Turkey (Türkiye)

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Konya, 42075, Turkey (Türkiye)

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Mersin, 33079, Turkey (Türkiye)

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Edinburgh, EH16 4TJ, United Kingdom

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Glasgow, United Kingdom

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Liverpool, L9 7AL, United Kingdom

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London, E2 9JX, United Kingdom

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London, NW3 2PF, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Related Publications (5)

• Facius A, Marostica E, Gardiner P, Watz H, Lahu G. Pharmacokinetic and Pharmacodynamic Modelling to Characterize the Tolerability of Alternative Up-Titration Regimens of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease. Clin Pharmacokinet. 2018 Aug;57(8):1029-1038. doi: 10.1007/s40262-018-0671-4.

  PMID: 29797235 DERIVED

• Martinez FJ, Rabe KF, Calverley PMA, Fabbri LM, Sethi S, Pizzichini E, McIvor A, Anzueto A, Alagappan VKT, Siddiqui S, Reisner C, Zetterstrand S, Roman J, Purkayastha D, Bagul N, Rennard SI. Determinants of Response to Roflumilast in Severe Chronic Obstructive Pulmonary Disease. Pooled Analysis of Two Randomized Trials. Am J Respir Crit Care Med. 2018 Nov 15;198(10):1268-1278. doi: 10.1164/rccm.201712-2493OC.

  PMID: 29763572 DERIVED

• Rabe KF, Calverley PMA, Martinez FJ, Fabbri LM. Effect of roflumilast in patients with severe COPD and a history of hospitalisation. Eur Respir J. 2017 Jul 5;50(1):1700158. doi: 10.1183/13993003.00158-2017. Print 2017 Jul. No abstract available.

  PMID: 28679611 DERIVED

• Martinez FJ, Calverley PM, Goehring UM, Brose M, Fabbri LM, Rabe KF. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet. 2015 Mar 7;385(9971):857-66. doi: 10.1016/S0140-6736(14)62410-7. Epub 2015 Feb 13.

  PMID: 25684586 DERIVED

• Calverley PM, Martinez FJ, Fabbri LM, Goehring UM, Rabe KF. Does roflumilast decrease exacerbations in severe COPD patients not controlled by inhaled combination therapy? The REACT study protocol. Int J Chron Obstruct Pulmon Dis. 2012;7:375-82. doi: 10.2147/COPD.S31100. Epub 2012 Jun 20.

  PMID: 22791991 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Roflumilast

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: AstraZeneca Clinical Study Information Center
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• AstraZeneca AstraZeneca

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 5, 2011
• Study Start: May 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: May 1, 2014
• Last Updated: December 13, 2016
• Results First Posted: October 29, 2015

Record last verified: 2016-09

Locations

FR (5); RU (19); GB (6); ZA (10); SL (9); HU (13); PL (15); GR (8); AU (8); DK (4); KR (7); BE (5); IT (8); TU (7); NL (6); CA (8); BR (8); IL (13); ES (7); DE (10)