Trial to Assess the Anti-inflammatory Effects of Roflumilast in Chronic Obstructive Pulmonary Disease

NCT ID: NCT01509677

Last Updated: 2019-11-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-01
• Study Completion Date: 2016-02-01

Brief Summary

The objective of the Biopsy trial is to investigate the effect of roflumilast 500 µg tablets once daily versus placebo on inflammation parameters in bronchial biopsy tissue specimen and additional in sputum and blood serum. Also data on safety status will be obtained.

Patients to be included required to have moderate to severe COPD associated with chronic bronchitis. The total duration of this randomized, multicentre, phase III trial is 24 weeks maximum.

Detailed Description

This was a multicenter, double-blind, randomized, parallel group, phase 3 study. Patients included had a history of COPD (GOLD stage II-III, in Germany stage II only) with chronic productive cough.

There were 2 parallel treatment arms (placebo and roflumilast 500 μg once daily). A 1 to 1 randomization scheme was used, that is, patients were allocated to roflumilast 500 μg or placebo in equal proportions. Randomization was stratified by concomitant LABA use.

The total duration of this study was 24 weeks maximum per patient. The study consisted of the following periods:

• Single-blind placebo run-in period (6 weeks) with visits at Week -6 (visit 0 [V0]), Week -2 (V1), and Week 0 (V2, randomization visit), during which all patients received placebo.
• Double-blind treatment period (16 weeks) during which patients received either roflumilast or matching placebo with visits at Week 6 (V4), Week 14 (V5), and Week 16 (V6).

An additional visit (V3) within 2 weeks after bronchoscopy/bronchial biopsy was performed purely as a safety visit. The exact timing of this safety visit was to be determined by the investigator. Safety follow-up. All AEs were followed up to 30 days after the double-blind treatment period. An additional safety visit, V7, was scheduled within 2 weeks after the second bronchoscopy. The exact timing of the safety visit was to be determined by the investigator.

Patients were required not to take any food or drink overnight for at least 8 hours prior to returning to the study center for each visit. Patients were also asked to avoid strenuous exercise for 8 hours prior to each study visit and to avoid smoking for 4 hours prior to each study visit.

For visits where patients did not undergo blood collections or biopsies, the fasting requirement was only mandated if clinically indicated, per investigator judgment.

Conditions

COPD; Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Roflumilast

500 μg tablet, once daily, oral administration in the morning after breakfast

Group Type: ACTIVE_COMPARATOR

Roflumilast

Intervention Type: DRUG

500 μg tablet, once daily, oral administration in the morning after breakfast

Placebo

tablet, once daily, oral administration in the morning after breakfast

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

tablet, once daily, oral administration in the morning after breakfast

Interventions

Roflumilast

500 μg tablet, once daily, oral administration in the morning after breakfast

Intervention Type: DRUG

Placebo

tablet, once daily, oral administration in the morning after breakfast

Intervention Type: DRUG

Other Intervention Names

Daxas; Placebo to Roflumilast

Eligibility Criteria

Inclusion Criteria

• 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 at least three months in each of the two years prior to baseline visit V0 (with other causes of productive cough excluded)
• Outpatients 40-80 years of age
• Post-bronchodilator 30% ≤FEV1 ≤80% predicted
• Post-bronchodilator FEV1/FVC ratio ≤70%
• Current or former smokers with smoking history ≥20 pack years

Exclusion Criteria

• Criteria affecting the read-out parameters of the trial:

• Clinical instability, defined as experiencing a COPD exacerbation six months prior to V0
• An upper/lower respiratory tract infection which has not resolved four weeks prior to V0
• Diagnosis of asthma and/or other relevant lung disease
• Known alpha-1-antitrypsin deficiency
• Suspicion or diagnosis of a bleeding disorders irrespective of its pathophysiological mechanism

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AstraZeneca AstraZeneca

Role: STUDY_DIRECTOR

AstraZeneca

Locations

København NV, , Denmark

København NV, , Denmark

Freiburg im Breisgau, , Germany

Großhansdorf, , Germany

Hanover, , Germany

Heidelberg, , Germany

Immenhausen, , Germany

Kiel, , Germany

Mainz, , Germany

Bialystok, , Poland

Krakow, , Poland

Lodz, , Poland

Lodz, , Poland

Lund, , Sweden

Cottingham, , United Kingdom

Dafen, , United Kingdom

Leicester, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Norwich, , United Kingdom

Countries

Denmark; Germany; Poland; Sweden; United Kingdom

References

Rabe KF, Watz H, Baraldo S, Pedersen F, Biondini D, Bagul N, Hanauer G, Gohring UM, Purkayastha D, Roman J, Alagappan VKT, Saetta M. Anti-inflammatory effects of roflumilast in chronic obstructive pulmonary disease (ROBERT): a 16-week, randomised, placebo-controlled trial. Lancet Respir Med. 2018 Nov;6(11):827-836. doi: 10.1016/S2213-2600(18)30331-X. Epub 2018 Sep 14.

Reference Type: DERIVED

PMID: 30224319 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4560&filename=RO-2455-402-RD_ROBERT_Updated_Protocol_v6.0_(Amendment_12)_-_Redacted.pdf

RO-2455-402-RD Updated Protocol v 6.0 (Amendment 12)

Other Identifiers

2011-000582-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1155-8767

Identifier Type: REGISTRY

Identifier Source: secondary_id

D7120C00003

Identifier Type: OTHER

Identifier Source: secondary_id

RO-2455-402-RD

Identifier Type: -

Identifier Source: org_study_id