Study to evaluate the effect of fluticasone furoate/vilanterol on survival in subjects with chronic obstructive pulmonary disease

• Register: EUCTR
• Last refreshed on: 12 October 2015
• Main ID: EUCTR2010-021638-72-NL
• Date of registration: 19/09/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: Study to evaluate the effect of fluticasone furoate/vilanterol on survival in subjects with chronic obstructive pulmonary disease
• Scientific title: HZC113782: A Clinical Outcomes Study to compare the effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg with placebo on Survival in Subjects with moderate Chronic Obstructive Pulmonary Disease (COPD) and a history of or at increased risk for cardiovascular disease. - HZ COPD Mortality Study
• Date of first enrolment: 20/12/2013
• Target sample size: 16000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021638-72
• 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: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czech Republic, Denmark, France, Georgia, Germany, Greece, Hungary, India, Indonesia, Israel, Italy, Japan, Korea, Republic of, Latvia, Macedonia, the former Yugoslav Republic of, Malaysia, Mexico, Netherlands, Pakistan, Philippines, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Type of subject: outpatient.
2. Informed consent: Subjects must give their signed and dated written informed
consent to participate.
3. Gender: Male or female. Female subjects must be post-menopausal or using a highly
effective method for avoidance of pregnancy. The decision to include or exclude
women of childbearing potential may be made at the discretion of the investigator in
accordance with local practice in relation to adequate contraception.
4. Age: =40 and = 80 years of age at Screening (Visit 1).
5. Tobacco use: Subjects with a current or prior history of =10 pack-years of cigarette
smoking at screening (Visit 1). Previous smokers are defined as those who have
stopped smoking for at least 6 months prior to Visit 1.
6. Airflow Obstruction
• Subjects with a measured post-albuterol/salbutamol FEV1 =50 and =70% of
predicted normal values calculated using NHANES III reference equations
[Hankinson, 1999; Hankinson, 2010] at Screening (Visit 1).
Post-bronchodilator spirometry will be performed approximately 15 minutes
after the subject has self-administered 4 inhalations (i.e., total 400mcg) of
albuterol/salbutamol via an MDI with a valved-holding chamber. The
FEV1/FVC ratio and FEV1 percent predicted values will be calculated.
7. Dyspnea:
Subjects must score 2 or higher on the modified Medical Research Council Dyspnea
scale (Visit 1)
8. Cardiovascular disease:
For patients >= 40 years of age: any one of the following:
Established (i.e. by clinical signs or imaging studies) coronary artery
disease (CAD)
Established (i.e. by clinical signs or imaging studies) peripheral arterial
disease (PAD)
Previous stroke
Previous MI
Diabetes mellitus with target organ disease
OR
For patients >=60 years of age: any 2 of the following:
Being treated for hypercholesterolemia
Being treated for hypertension
Being treated for diabetes mellitus
Being treated for peripheral vascular disease
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8000

Exclusion criteria:
1. Pregnancy: Women who are pregnant or lactating.
2. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
asthma are eligible if they also have a current diagnosis of COPD).
3. a1-antitrypsin deficiency: Subjects with known a-1 antitrypsin deficiency as the
underlying cause of COPD.
4. Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial
lung diseases or other active pulmonary diseases.
5. Lung resection or transplantation: Subjects with lung volume reduction surgery
within the 12 months prior to Screening or having had a lung transplant.
6. A moderate/severe COPD exacerbation that has not resolved at least 14 days prior to Visit 1 and at least 30 days following the last dose of oral corticosteroids (if
applicable).
7. Current severe heart failure (New York Heart Association class IV). Subjects will also be excluded if they have a known ejection fraction of <30% or if they have an
implantable cardioverter defibrillator (ICD).
8. Other diseases/abnormalities: Any life-threatening condition with life expectancy
<3 years, other than vascular disease or COPD, that might prevent the subject from
completing the study.
9. End stage chronic renal disease: Subjects will be excluded if on renal replacement
therapy (hemodialysis or peritoneal).
10. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study
medications (e.g. beta-agonists, corticosteroid) or components of the inhalation
powder (e.g. lactose, magnesium stearate). In addition, patients with a history of
severe milk protein allergy that, in the opinion of the study physician, contraindicates
the subject’s participation will also be excluded.
11. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
12. Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy
(LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day.
Oxygen prn use (i.e. =12 hours per day) is not exclusionary.
13. Questionable validity of consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation or other conditions that will limit the validity
of informed consent to participate in the study or the potential compliance to study
procedures.
14. Affiliation with investigator site: Study investigators, sub-investigators, study
coordinators, employees of a participating investigator or immediate family members
of the aforementioned are excluded from participating in this study.
15. Additional medication: Use of the following medications within the following time
intervals prior to Visit 1 or during the study (unless otherwise specified): view protocol page 23 for further information.


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

Health Condition(s) or Problem(s) studied

Subjects with moderate Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 16.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

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

Intervention(s)

Trade Name: Breo Ellipta
Product Name: Fluticasone Furoate/GW642444 Inhalation Powder
Product Code: Fluticasone Furoate/GW642444 Inhalation Powder
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Fluticasone furoate
CAS Number: 397864-44-7
Current Sponsor code: GW685698X
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: Vilanterol trifenatate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Product Name: Fluticasone Furoate Inhalation Powder
Product Code: GW685698X
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Fluticasone furoate
CAS Number: 397864-44-7
Current Sponsor code: GW685698X
Other descriptive name: Fluticasone Furoate
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Product Name: Vilanterol (GW642444) Inhalation Powder
Product Code: Vilanterol (GW642444) Inhalation Powder
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: Vilanterol (GW642444M)
CAS Number: 503070-58-4
Current Sponsor code: GW642444
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Primary end point(s): Primary Efficacy Endpoint
• Time to death from any cause

Secondary Objective: • To evaluate the effect of FF/VI compared with placebo on the rate of decline in
FEV1
• To evaluate the effect of FF/VI compared with placebo on a cardiovascular
composite endpoint comprised of on-treatment CV death, myocardial infarction
, stroke, unstable angina and TIA.

Timepoint(s) of evaluation of this end point: Every 3 months for the duration of the study

Main Objective: The primary objective of this study is to prospectively evaluate the effect of Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25mcg QD compared with placebo on survival in subjects with moderate COPD (=50 and =70 % predicted FEV1) and a history of, or at increased risk for developing, cardiovascular disease.

Secondary Outcome(s)

Secondary end point(s): • Rate of decline in FEV1
• Time to CV event

Timepoint(s) of evaluation of this end point: rate of decline in FEV1 - only while on treatment
time to CV event - on and off treatment as we are doing for mortality

Secondary ID(s)

NCT01313676

N/A

HZC113782

2010-021638-72-CZ

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Ltd