Effect of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease

NCT01473758 | Terminated Phase 2 Results

• 4 other identifiers: RO-2455-405-RD2011-002905-31U1111-1137-402311/SC/0494
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this trial is to investigate if roflumilast can reduce the neutrophilic inflammation at acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD). In addition, the potential benefit of roflumilast on severity and recovery periods of acute COPD exacerbations will be assessed using patient diaries and questionnaires.

Conditions

Chronic Obstructive Pulmonary Disease With (Acute) Exacerbation

Keywords

COPD; Chronic obstructive pulmonary disease; Roflumilast

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Initial Approach)

  Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.

  Baseline and Day 14

• Change From Baseline in Sputum Neutrophil Counts at Day 14 Post Exacerbation (Extended Approach)

  Sputum samples were collected and processed at the investigational site according to their standard procedures. Total cell count (absolute number of nonsquamous cells per gram of the original sputum sample) were determined using a Neubauer hemocytometer. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used with neutrophil count at Baseline and treatment as independent variables, fixed effects.

  Baseline and Day 14

Secondary Outcomes (56)

• Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Initial Approach)

  Day 14

• Percentage of Participants Whose Sputum Neutrophil Counts Returned to Stable State at Day 14 (Extended Approach)

  Day 14

• Change From Baseline in Sputum Marker Total Cells (Initial Approach)

  Baseline and Day 7, Day 14, Day 28 and Day 56

• Change From Baseline in Sputum Marker Total Cells (Extended Approach)

  Baseline and Day 7, Day 14, Day 28 and Day 56

• Change From Baseline in Sputum Marker Percentage of Neutrophils (Initial Approach)

  Baseline and Day 7, Day 14, Day 28 and Day 56

Study Arms (2)

Roflumilast

ACTIVE COMPARATOR

added on to standard therapy for acute COPD exacerbations

Drug: Roflumilast

Placebo

PLACEBO COMPARATOR

added on to standard therapy for acute COPD exacerbations

Drug: Placebo

Interventions

Roflumilast DRUG

500 µg tablet, od, oral administration in the morning after breakfast

Roflumilast

Placebo DRUG

tablet, od, oral administration in the morning after breakfast

Placebo

Eligibility Criteria

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

You may qualify if:

• Written informed consent (IC)
• Age ≥ 40 years
• History of COPD for at least 12 months prior to enrollment (Visit V0)
• Chronic productive cough for 3 months in each of the 2 years prior to enrollment (if other causes of productive cough have been excluded) and/or an exacerbation with predominantly bronchitic symptoms at enrollment
• Presentation of an acute exacerbation of COPD that will be associated with increased sputum volume or change in sputum colour
• Documented fixed airway obstruction determined by an FEV1/FVC ratio (post-bronchodilator) \< 70% (if a pulmonary function test is not possible at Visit V0 a previous measurement can be taken which must not be older than 6 months)
• Former smoker (defined as: smoking cessation at least 1 year ago) or current smoker both with a smoking history of at least 10 pack years

You may not qualify if:

• Diagnosis of asthma and/or other relevant lung disease
• Known alpha-1-antitrypsin deficiency
• Recurrent exacerbations (within 8 weeks of a preceding exacerbation)
• Treatment of current exacerbation with oral corticosteroids and/or antibiotics already started at enrollment
• Treatment with PDE4 inhibitors within 3 months prior to Visit V0

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Academic Unit of Respiratory Medicine, Royal Free Hospital, Jadwiga A. Wedzicha

London, NW3 2PF, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Related Publications (1)

• Mackay AJ, Patel ARC, Singh R, Sapsford RJ, Donaldson GC, Prasad N, Goehring UM, Nip TK, Wedzicha JA. Randomized Double-Blind Controlled Trial of Roflumilast at Acute Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017 Sep 1;196(5):656-659. doi: 10.1164/rccm.201612-2518LE. No abstract available.

  PMID: 28146642 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: Medical Director, Clinical Science
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2011
• First Posted: November 17, 2011
• Study Start: February 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: February 14, 2017
• Results First Posted: October 24, 2016

Record last verified: 2016-08

Locations

GB (2)