Clinical trial NCT00527826: 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
Official title: A 12 Month Open-label Randomized Parallel Group Study to Investigate the Influence of Salmeterol Xinafoate/Fluticasone Propionate Either in Fixed Combination or Separately Via Diskus Inhalers on the Course of the Disease and Frequency of Exacerbations in Subjects With Severe and Very Severe COPD.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
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
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-09-11
Enrollment: 214
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: A 12 month open-label randomized parallel group study to investigate the influence of salmeterol xinafoate/fluticasone propionate either in fixed combination (SFC50/500 µg bid) or separately (SAL 50 µg and FP 500 µg bid) via Diskus inhalers on the course of the disease and frequency of exacerbations in subjects with severe and very severe COPD ( GOLD stage III+IV)

Eligibility criteria: Inclusion criteria:

* 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.

Exclusion criteria:

* 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

Primary outcomes:
measure: Mean Number of Exacerbations Per Year: Negative Binomial Model
timeFrame: Baseline through Week 52
measure: Mean Number of Exacerbations Per Year: Poisson Model
timeFrame: Baseline through Week 52
Secondary outcomes:
measure: Compliance and Adherence to Study Medication
timeFrame: Baseline through Week 52
measure: Mean Number of COPD-related Visits at/by Physician
timeFrame: Baseline through Week 52
measure: Number of Participants With the Indicated Number of Days at the Intensive Care Unit (ICU)
timeFrame: Baseline through Week 52
measure: Number of Participants With the Indicated Number of Hospital Stays
timeFrame: Baseline through Week 52
measure: Mean Number of Days Rescue Medication Was Used
timeFrame: The 7 days before baseline (=Visit 2 [Week 8]) and the last 7 days of study (=Visit 6 [Week 52])
measure: Mean Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52
timeFrame: Baseline and Week 52
measure: Mean Change From Baseline in Inspiratory Vital Capacity (IVC) at Week 52
timeFrame: Baseline and Week 52
measure: Mean Change From Baseline in the Tiffeaneau Index at Week 52
timeFrame: Baseline and Week 52
measure: Mean Change From Baseline in the Symptom Score of the St. George's Respiratory Questionnaire (SGRQ) at Week 52
timeFrame: Baseline and Week 52
measure: Mean Change From Baseline in the Activity Score of the St. George's Respiratory Questionnaire (SGRQ) at Week 52
timeFrame: Baseline and Week 52
measure: Mean Change From Baseline in the Impact Score of the St. George's Respiratory Questionnaire (SGRQ) at Week 52
timeFrame: Baseline and Week 52
measure: Mean Change From Baseline in the Total Score of the St. George's Respiratory Questionnaire (SGRQ) at Week 52
timeFrame: Baseline and Week 52
measure: Mean Total Costs (Related to COPD) Per Participant
timeFrame: Baseline through Week 52
Other outcomes:
Locations:
city: Bruchsal
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Wiesloch
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Cottbus
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Neuruppin
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Potsdam
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Eschwege
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Gelnhausen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Kassel
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Marburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Guetersloh
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Saarbruecken
country: Germany
facility: GSK Investigational Site
state: Saarland
city: Annaberg
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Radebeul
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Schmoelln
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.