Influence Of Salmeterol Xinafoate/Fluticasone Propionate (50/500 µg BID) On The Course Of The Disease And Exacerbation Frequency In COPD Patients Gold Stage III And IV

NCT00527826 | Completed Phase 4 Results

• 1 other identifier: SCO107227
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 23

Brief Summary

This is a 12 month randomized, open-label, parallel-group study to obtain data on the frequency and variability of exacerbations in severe and very severe Chronic Obstructive Pulmonary Disease (COPD) patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage III and IV) receiving salmeterol xinafoate and fluticasone propionate either in fixed combination (SFC) or from separate inhalers (Sal/FP) with standard therapy. 200 subjects will be enrolled in approximately 30 study centres in Germany. Data on health care utilisation will be collected to compare direct costs associated with COPD in these two groups. Baseline data will be collected for all subjects at Visit 1 and eligible subjects will be randomized to receive either SFC 50/500 µg bid (twice daily) as fixed combination or Sal 50 µg bid (twice daily) and FP 500 µg bid (twice daily) concurrently over 52 weeks. Subjects will return for study visits every two to three months until week 52. Additional telephone calls will be made between scheduled visits every 4 weeks. Assessments will include monitoring of frequency of exacerbations, health care utilisation (including emergency visits and hospitalizations) and rescue medication, lung function, drug compliance, health-related quality of life (SGRQ = St George's Respiratory Questionnaire) and safety.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Severe and very severe COPD (GOLD stage III / IV) exacerbations; health care utilisation; Chronic Obstructive Pulmonary Disease (COPD); quality of life; compliance; salmeterol/fluticasone combination

Outcome Measures

Primary Outcomes (2)

• Mean Number of Exacerbations Per Year: Negative Binomial Model

  During regular visits, participants were asked whether they experienced any exacerbation since last contact. Between visits, COPD participants were contacted by phone by the staff and asked about exacerbation details. Exacerbations were defined according to Rodriguez-Roisin: moderate (grade II) exacerbations include a worsening of COPD symptoms that require both a change of respiratory medication (increased dose of prescribed or addition of new drugs) and medical assistance; severe (grade III) exacerbations include deterioration in COPD resulting in hospitalization or emergency room treatment.

  Baseline through Week 52

• Mean Number of Exacerbations Per Year: Poisson Model

  During regular visits, participants were asked whether they experienced any exacerbation since last contact. Between visits, COPD participants were contacted by phone by the staff and asked about exacerbation details. Exacerbations were defined according to Rodriguez-Roisin: moderate (grade II) exacerbations include a worsening of COPD symptoms that require both a change of respiratory medication (increased dose of prescribed or addition of new drugs) and medical assistance; severe (grade III) exacerbations include deterioration in COPD resulting in hospitalization or emergency room treatment.

  Baseline through Week 52

Secondary Outcomes (13)

• Compliance and Adherence to Study Medication

  Baseline through Week 52

• Mean Number of COPD-related Visits at/by Physician

  Baseline through Week 52

• Number of Participants With the Indicated Number of Days at the Intensive Care Unit (ICU)

  Baseline through Week 52

• Number of Participants With the Indicated Number of Hospital Stays

  Baseline through Week 52

• Mean Number of Days Rescue Medication Was Used

  The 7 days before baseline (=Visit 2 [Week 8]) and the last 7 days of study (=Visit 6 [Week 52])

Study Arms (2)

arm 1

ACTIVE COMPARATOR

Drug: Salmeterol / Fluticasone (50/500 µg) BID fixed combination

arm 2

ACTIVE COMPARATOR

Drug: Salmeterol / Fluticasone (50/500 µg) BID separate Inhalers

Interventions

Salmeterol / Fluticasone (50/500 µg) BID fixed combination DRUG

comparator

arm 1

Salmeterol / Fluticasone (50/500 µg) BID separate Inhalers DRUG

comparator

arm 2

Eligibility Criteria

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

You may qualify if:

• Subject must have a diagnosis of COPD based on the American Thoracic Society (ATS)/ European Respiratory Society (ERS) criteria.
• Male or female subjects, aged \>=40 years. Females must be of Non Child Bearing Potential. The definition of Non Child Bearing Potential is as following: Females, regardless of their age, with functioning ovaries and who have a current documented tubal ligation or hysterectomy, or females who are post-menopausal.
• Have diagnosed COPD stage III or IV according to GOLD criteria: a baseline post-bronchodilator Forced Expiratory Volume, measured at 1 second (FEV1) \<50% of predicted normal and a baseline post- bronchodilator FEV1/Inspiratory Vital Capacity (IVC) ratio \<70%.
• Have experienced at least 2 moderate or severe COPD exacerbations leading to medical consultation (requiring oral corticosteroids or increasing dosage of oral corticosteroids and/or antibiotics or hospitalization) within the 12 months preceding Visit 1.
• Have stable COPD medication within 4 weeks prior to Visit 1 (no new medication added and no dosage changes in medication).
• Current or ex-smokers with a smoking history of at least 10 pack years (number of pack years = \[number of cigarettes per day / 20\] x number of years smoked, e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years).
• Are currently managed at home (outpatients), are ambulatory and able to travel to the clinic. Subjects can be treated with all relevant COPD medication. This includes vaccines, inhaled short-acting beta-2-agonists as needed, short-acting or long-acting anticholinergics (tiotropium), systemic beta-2-agonists, theophylline, mucolytics, antioxidants, beta-1-agonists (for cardiovascular indication), non-invasive ventilation, long term oxygen therapy and can have Cor Pulmonale.
• A signed and dated written informed consent is obtained prior to participation.
• Able to comply with the requirements of the protocol and be available for study visits over 52 weeks.

You may not qualify if:

• Known other respiratory disorders or signs for other respiratory disorders (e.g. asthma, lung cancer, sarcoidosis, tuberculosis, lung fibrosis, cystic fibrosis, bronchoectasis).
• Known history of significant inflammatory disease, other than COPD (e.g. rheumatoid arthritis and systemic lupus erythematosus).
• Known to be severely alpha-1-antitrypsin deficient (PI SZ or ZZ)
• Having undergone lung surgery (e.g. lung resection including lung volume reduction surgery, lung transplant) or subjects scheduled for surgery.
• Concurrent medication from Visit 1 and for the duration of the study with any of the prohibited medications: monoamine oxidase inhibitors and tricyclic antidepressants, and ritonavir (a highly potent cytochrome P450 3A4 inhibitor).
• Subjects receiving chronic or prophylactic antibiotic therapy.
• Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study or impact on subject safety.
• Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.
• History of depression.
• History or presence of clinically significant drug sensitivity or clinically significant allergic reaction to corticosteroids or salmeterol.
• Moderate or severe COPD exacerbation (requiring corticosteroids or increased dosage of corticosteroids and/or antibiotics or hospitalization) within the 4 weeks prior to Visit 1
• Lower respiratory tract infection within the 4 weeks prior to Visit 1 .
• Pregnant or lactating female and female of childbearing potential.
• Subject is a participating investigator, sub-investigator, study coordinator, or other employee of a participating investigator, or is an immediate family member of the before mentioned. Subject is an employee of GlaxoSmithKline (GSK).
• Subject participated in an investigational drug study within 30 days prior to Visit 1

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (23)

GSK Investigational Site

Bruchsal, Baden-Wurttemberg, 76646, Germany

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69117, Germany

Location

GSK Investigational Site

Mannheim, Baden-Wurttemberg, 68161, Germany

Location

GSK Investigational Site

Wiesloch, Baden-Wurttemberg, 69168, Germany

Location

GSK Investigational Site

Cottbus, Brandenburg, 03050, Germany

Location

GSK Investigational Site

Neuruppin, Brandenburg, 16816, Germany

Location

GSK Investigational Site

Potsdam, Brandenburg, 14469, Germany

Location

GSK Investigational Site

Hamburg, Hamburg, 22299, Germany

Location

GSK Investigational Site

Eschwege, Hesse, 37269, Germany

Location

GSK Investigational Site

Gelnhausen, Hesse, 63571, Germany

Location

GSK Investigational Site

Kassel, Hesse, 34121, Germany

Location

GSK Investigational Site

Marburg, Hesse, 35037, Germany

Location

GSK Investigational Site

Wiesbaden, Hesse, 65183, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30169, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44787, Germany

Location

GSK Investigational Site

Gütersloh, North Rhine-Westphalia, 33330, Germany

Location

GSK Investigational Site

Saarbrücken, Saarland, 66111, Germany

Location

GSK Investigational Site

Annaberg, Saxony, 09456, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04275, Germany

Location

GSK Investigational Site

Radebeul, Saxony, 01445, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10365, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 13187, Germany

Location

GSK Investigational Site

Schmölln, Thuringia, 04626, Germany

Location

Related Publications (1)

• Hagedorn C, Kassner F, Banik N, Ntampakas P, Fielder K. Influence of salmeterol/fluticasone via single versus separate inhalers on exacerbations in severe/very severe COPD. Respir Med. 2013 Apr;107(4):542-9. doi: 10.1016/j.rmed.2012.12.020. Epub 2013 Jan 20.

  PMID: 23337300 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Patient Compliance

Interventions

Salmeterol Xinafoate; Fluticasone

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2007
• First Posted: September 11, 2007
• Study Start: November 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: October 30, 2012
• Results First Posted: June 24, 2010

Record last verified: 2012-10

Locations

DE (23)