Roflumilast Safety Administered Once a Day on Alternate Days for Two Weeks Compared to the Usual Dosage Once Daily (ROFLU2011)

Clinical Trial Phase III Blind, Parallel Group to Analyze Differences in the Safety of Roflumilast Administered Once a Day on Alternate Days for Two Weeks Compared to the Usual Dosage Once Daily

It is a phase IV clinical trial: longitudinal, prospective, evaluator-blind, randomized into 2 groups of patients with chronic obstructive pulmonary disease (COPD). The intervention group was based on the administration of roflumilast 500 mcg per day on alternate days (roflumilast 500μg eod) for 2 weeks (phasing). In the control group assigned to undertake the treatment according to the standard dosage (roflumilast 500μg od).

The patient monitoring will be done by one of the sub-investigators fully independent team that started the medication keeping the pattern masking by single blind, and since it aims to assess the frequency of adverse events (AEs) in both groups were collected systematically different AEs and their characteristics at 15 days (V1), and from that moment a month (V2) and 2 months (V3). Likewise, other data collected (functional demographic, comorbidities, home treatment, anxiety and depression and quality of life).

The purpose of this study is to assess whether the administration of roflumilast by a gradual pattern varies the incidence of discontinuations due to adverse events when compared with the usual dosage.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Roflumilast alternated days; Drug: Roflumilast 500 mcg per day

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • Granada, Spain
    • H.U. Virgen de las Nieves
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain
      • Hospital de Jerez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of COPD in severe degree GOLD criteria, assessed by post-bronchodilator spirometry (FEV1 <50%, FEV1/Forced vital capacity (FVC) <70% of theory).
• Age over 18 years.
• Productive cough recurrently most days for at least three months a year and at least 2 consecutive years.
• History from smoking prior> 15 to 20 packs / year.
• An exacerbation in the previous year.
• Stability clinic in the last 30 days.

Exclusion Criteria:

• Pregnancy / breastfeeding.
• Acute infections.
• Patients with severe mental disorder or uncontrolled, in the opinion of the investigator, would make the patient has a higher risk due to their participation in the study, could be a confounding factor in the study's results or is likely to prevent that the patient meets the requirements of the study or to complete the study.
• Patients cachectic or the risk of cachexia.
• HIV infection.
• Severe immune Infections (systemic lupus erythematosus, multiple sclerosis, etc.).
• Gastroesophageal reflux symptoms and diagnosis established.
• Hiatal hernia.
• Peptic ulcer disease.
• Inflammatory bowel pathology.
• Neoplastic pathology: current diagnosis of cancer other than basal cell or squamous cell carcinoma of the skin.
• Moderate to severe hepatic impairment (Child-Pugh BC).
• Inability to understand / perform the techniques.
• Home treatment with theophylline, methotrexate, azathioprine, infliximab, etanercept, inducers of cytochrome P450 (eg, rifampicin, phenobarbital, carbamazepine, phenytoin),cytochrome P450 3A4 (CYP3A4) inhibitors (erythromycin and ketoconazole), oral contraceptives (gestodene and ethinyl estradiol), making prolonged oral corticosteroids, or a drug that contains fluvoxamine, enoxacin and cimetidine.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Roflumilast alternated days; Intervention: 500 mcg per day on alternate days (roflumilast 500μg eod) for 2 weeks	Drug: Roflumilast alternated days; 500 mcg per day on alternate days (roflumilast 500μg eod) for 2 weeks; Other Names: schedule change
Active Comparator: Roflumilast 500 mcg per day; Roflumilast 500μg standard dosage	Drug: Roflumilast 500 mcg per day; Other Names: Standard dosage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of Adverse Events	Difference in the proportion of patients who leave the study for AEs between the control group (roflumilast 500μg od) and intervention (roflumilast 500μg eod)	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients who leave the study	Difference in the proportion of patients who leave the study for AEs between the control group (roflumilast 500μg od) alternating pattern (in patients with impaired tolerance) and intervention (roflumilast 500μg eod) between visits V2 and V0.	two weeks

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza Progreso y Salud
• Investigators: Study Chair: Teodoro Montemayor Rubio, M.D. Ph D, Hospital Universitario Virgen Macarena; Principal Investigator: Ruth Ayerbe, M.D, Complejo Hospitalario de Especialidades Juan Ramón Jiménez; Principal Investigator: Gregorio Soto, M.D., Hospital de Jerez; Principal Investigator: Francisco L Muñoz, M.D., Hospital Universitario Reina Sofia; Principal Investigator: Concepción Morales, M.D., H.U. Virgen de las Nieves; Principal Investigator: José L de la Cruz, M.D., Complejo Hospitalario Carlos Haya; Principal Investigator: Cristina García, M.D., Hospital Universitario de Puerto Real; Principal Investigator: Bernardino Alcázar, M.D., HAR de Loja; Principal Investigator: Rosa Vazquez, M.D., Hospital Infanta Elena

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: May 6, 2013
• First Submitted That Met QC Criteria: May 7, 2013
• First Posted (Estimate): May 8, 2013

Study Record Updates

• Last Update Posted (Estimate): July 8, 2015
• Last Update Submitted That Met QC Criteria: July 7, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: ROFLU2011