A 12 month study to compare FF/UMEC/VI with FF/VI and UMEC/VI in patients with Chronic Obstructive Pulmonary Disease(COPD) and a history of COPD exacerbation

• Register: EUCTR
• Last refreshed on: 30 October 2017
• Main ID: EUCTR2013-003075-35-PL
• Date of registration: 02/07/2014
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: A 12 month study to compare FF/UMEC/VI with FF/VI and UMEC/VI in patients with Chronic Obstructive Pulmonary Disease(COPD) and a history of COPD exacerbation
• Scientific title: A phase III, 52 week, randomized, double-blind, 3-arm parallel group study, comparing the efficacy, safety and tolerability of the fixed dose triple combination FF/UMEC/VI with the fixed dose dual combinations of FF/VI and UMEC/VI, all administered once-daily in the morning via a dry powder inhaler in subjects with chronic obstructive pulmonary disease - 12m, Phase III, FF/UMEC/VI vs FF/VI and UMEC/VI COPD exacerbation trial
• Date of first enrolment: 19/08/2014
• Target sample size: 10000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003075-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Croatia, Czech Republic, Denmark, Finland, France, Germany, Hong Kong, Israel, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Peru, Poland, Puerto Rico, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Clincial Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: Clincial Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Informed Consent: A signed and dated written informed consent prior to study participation.
2. Type of subject: Outpatient.
3. Age: Subjects 40 years of age or older at Visit 1.
4. Gender: Male or female subjects.
A female is eligible to enter and participate in the study if she is of:
Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, > 45 years, in the absence of hormone replacement therapy.
OR
Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study – screening to safety follow-up contact):
- Abstinence
- Oral Contraceptive, either combined or progestogen alone
- Injectable progestogen
- Implants of levonorgestrel
- Estrogenic vaginal ring
- Percutaneous contraceptive patches
- Intrauterine device (IUD) or intrauterine system (IUS)
- Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, “documented” refers to the outcome of the investigator's/designee’s medical examination of the subject
or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records.
- Double barrier method: condom and an occlusive cap (diaphragm or
cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
5. COPD Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004].
6. Smoking History: Current or former cigarette smokers with a history of cigarette smoking of =10 pack-years at screening (visit 1) [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)]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or
cigar use cannot be used to calculate pack-year history
7. Severity of COPD symptoms: A score of =10 on the COPD Assessment Test (CAT) at screening.
8. Severity of COPD Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 at Screening.
9. Existing COPD maintenance treatment: Subject must be receiving daily maintenance treatment for their COPD for at least 3 months prior to Screening. Note: Subjects receiving only PRN COPD medications are not eligible.
10. History of Exacerbations: Subjects must demonstrate:
a post-bronchodilator FEV1 < 50% predicted normal and a documented history of = 1 moderate or severe COPD exacerbation in the previous 12 months
OR
a post-bronchodilator 50% =FEV1 < 80% predicted normal and a documented history of = 2 moderate exacerbations or a documented history of =1 severe COPD exacerbation (hospitalized) in the previous 12 months.
Note: Percent predicted will be cal
Exclusion criteria:
1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
2. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
3. a1-antitrypsin deficiency: Subjects with a1-antitrypsin deficiency as the underlying cause of COPD.
4. Other respiratory disorders: Subjects with active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.
5. Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening.
6. Risk Factors for Pneumonia: immune suppression (e.g. HIV, Lupus) or other risk factors for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson’s Disease, Myasthenia Gravis) Patients at potentially high risk (e.g. very low BMI, severely malnourished, or very low FEV1) will only be included at the discretion of the Investigator.
7. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable). In addition, any subject that experiences pneumonia and/or moderate or severe COPD exacerbation during the run-in period will be excluded.
8. Other Respiratory tract infections that have not resolved at least 7 days prior to screening.
9. Abnormal Chest x-ray: Chest x-ray (posteroanterior and lateral) reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD, or another condition that would hinder the ability to detect an infiltrate on CXR (e.g. significant cardiomegaly, pleural effusion or scarring). All
subjects will have a chest x-ray at Screening Visit 1 (or historical radiograph or CT scan obtained within 3 months prior to screening) that will be over-read by a central vendor. Note: Subjects who have experienced pneumonia and/or moderate or severe COPD exacerbation within 3 months of screening must provide a post
pneumonia/exacerbation chest x-ray to be over-read by the central vendor or have a chest x-ray conducted at screening.
For sites in Germany: If a chest x-ray (or CT scan) within 3 months prior to Screening (Visit 1) is not available, approval to conduct a diagnostic chest x-ray will need to be obtained from the Federal Office for Radiation Protection (BfS).
10. Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any
disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
11. Unstable liver disease as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert’s
syndrome or asymptomatic gallstones). Note: Chronic stable hepatitis B and C are
acceptabl

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 17.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: Fluticasone Furoate/Umeclidinium/Vilanterol Trifenatate
Product Code: GSK2834425 (GW685698/GSK573719/GW642444)
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: FLUTICASONE FUROATE
CAS Number: 397864-44-7
Current Sponsor code: GW685698
Other descriptive name: Fluticasone Furoate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Umeclidinium
CAS Number: 869113-09-7
Current Sponsor code: GSK573719
Other descriptive name: GSK573719A
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 62.5-
INN or Proposed INN: Vilanterol Trifenatate
CAS Number: 503068-34-6
Current Sponsor code: GW642444
Other descriptive name: GW642444M
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Relvar Ellipta
Product Name: Fluticasone Furoate/Vilanterol Trifenatate
Product Code: GW685698/GW642444
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Fluticasone Furoate
CAS Number: 397864-44-7
Current Sponsor code: GW685698
Other descriptive name: Fluticasone Furoate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Vilanterol Trifenatate
CAS Number: 503070-58-4
Current Sponsor code: GW642444M
Other descriptive name: GW642444M
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Anoro
Product Name: Umeclidinium/Vilanterol Trifenatate
Product Code: GSK573719/GW642444
Pharmaceutical Form: Inhalation powder
INN or Proposed INN: Umeclidinium
CAS Number: 869113-09-7
Current Sponsor code: GSK573719
Other descriptive name: GSK573719A
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 62.5-
INN or Proposed INN: Vilanterol Trifenatate
CAS Number: 503068-34-6
Current Sponsor code: GW642444
Other descriptive name: GW642444M
Concentration unit: µg microgram(s)
Concentration type: equal
Concentratio

Primary Outcome(s)

Main Objective: To evaluate the efficacy of FF/UMEC/VI to reduce the annual rate of moderate and severe exacerbations compared with dual therapy of FF/VI or UMEC/VI in subjects with COPD.

Primary end point(s): Annual rate of on-treatment moderate and severe exacerbations comparing FF/UMEC/VI with UMEC/VI

Annual rate of on-treatment moderate and severe exacerbations comparing FF/UMEC/VI with FF/VI

Secondary Objective: -To evaluate the long term safety and other efficacy assessments of
FF/UMEC/VI compared with dual therapy of FF/VI or UMEC/VI.

-To evaluate the efficacy of FF/UMEC/VI to reduce exacerbations compared with UMEC/VI in the subset of subjects with a blood eosinophil count =150 cells/µl

Timepoint(s) of evaluation of this end point: Over 52 weeks

Secondary Outcome(s)

Secondary end point(s): • Change from baseline trough FEV1 at Week 52 comparing FF/UMEC/VI with FF/VI
• Change from baseline SGRQ Total Score at Week 52 comparing FF/UMEC/VI with FF/VI
• Time to first on-treatment moderate or severe exacerbation comparing FF/UMEC/VI with FF/VI and with UMEC/VI
• Annual rate of on-treatment moderate and severe exacerbations comparing FF/UMEC/VI with UMEC/VI in the subset of subjects with a blood eosinophil count =150 cells/µl
• Time to first on-treatment moderate or severe exacerbation comparing FF/UMEC/VI with UMEC/VI in the subset of subjects with a blood eosinophil count = 150 cells/µl
• Annual rate of on-treatment severe exacerbations comparing FF/UMEC/VI with FF/VI and with UMEC/VI

Timepoint(s) of evaluation of this end point: • Change from baseline trough FEV1 at Week 52 comparing FF/UMEC/VI with FF/VI
• Change from baseline SGRQ Total Score at Week 52 comparing FF/UMEC/VI with FF/VI
• Time to first on-treatment moderate or severe exacerbation comparing FF/UMEC/VI with FF/VI and with UMEC/VI
• Annual rate of on-treatment moderate and severe exacerbations comparing FF/UMEC/VI with UMEC/VI in the subset of subjects with a blood eosinophil count =150 cells/µl at Week 52
• Time to first on-treatment moderate or severe exacerbation comparing FF/UMEC/VI with UMEC/VI in the subset of subjects with a blood eosinophil count = 150 cells/µl
• Annual rate of on-treatment severe exacerbations comparing FF/UMEC/VI with FF/VI and with UMEC/VI at Week 52

Secondary ID(s)

CTT116855

2013-003075-35-NL

Source(s) of Monetary Support

GlaxoSmithKline, Research and Development Ltd