Clinical Trials Register

Summary
EudraCT Number:	2012-000927-42
Sponsor's Protocol Code Number:	HZC116601
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-09-13
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-000927-42

A.3

Full title of the trial

A Randomised, Double-Blind, Placebo-Controlled, Cross-Over, Single-Centre Study to Investigate the Acute Lung Deflation Effects of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg Once Daily on Cardiac Biventricular Function and Arterial Stiffness in Adults with Chronic Obstructive Pulmonary Disease (COPD)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of Fluticasone Furoate/Vilanterol in COPD, and the effects
of Reducing Lung Over-Inflation on the Heart

A.4.1

Sponsor's protocol code number

HZC116601

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Research and Development Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GSK
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline
B.5.2	Functional name of contact point	Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge Road
B.5.3.2	Town/ city	Uxbridge
B.5.3.3	Post code	UB11 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4402089904466
B.5.5	Fax number	+4402089901234
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Fluticasone Furoate/GW642444
D.3.2	Product code	Fluticasone Furoate/GW642444
D.3.4	Pharmaceutical form	Inhalation powder, pre-dispensed
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fluticasone Furoate
D.3.9.1	CAS number	397864-44-7
D.3.9.2	Current sponsor code	GW685698
D.3.9.3	Other descriptive name	Fluticasone Furoate
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Vilanterol trifenatate
D.3.9.1	CAS number	503070-58-4
D.3.9.2	Current sponsor code	GW642444M
D.3.9.3	Other descriptive name	Vilanterol trifenatate
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder, pre-dispensed
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Obstructive Pulmonary Disease (COPD)

E.1.1.1

Medical condition in easily understood language

Chronic Bronchitis

E.1.1.2

Therapeutic area

Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10010952
E.1.2	Term	COPD
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to test the hypothesis that lung hyperinflation contributes to cardiac dysfunction in COPD and that treatment of lung deflation with FF/VI Inhalation Powder 100/25 mcg administered once daily (QD) will result in the reversal of this cardiac dysfunction compared with placebo. This will be assessed by measures of right and left global and regional systolic and diastolic cardiac function as assessed using a 30 minute CMR.

E.2.2

Secondary objectives of the trial

A secondary objective will be to investigate the effect of FF/VI inhalation powder 100/25 mcg QD on measures of arterial stiffness in the form of pulse wave analysis and distensability in the pulmonary and systemic circulation.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Type of subject: Outpatient.
2. Informed consent: Subjects must give their signed and dated written informed consent to participate.
3. Gender: Males or females. 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 above
5. Smoking history of at least 15 pack years. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
6. Established diagnosis of COPD according to ATS/ERS criteria.
• Subjects with a measured post-albuterol/salbutamol FEV1 <70% of predicted normal values
• FEV1/FVC ratio after bronchodilator < 0.7
• Post-bronchodilator spirometry will be performed approximately 15 minutes after the subject has self-administered 4 inhalations (i.e., total 400mcg) of salbutamol via an MDI with a valved-holding chamber. The FEV1/FVC ratio and FEV1 percent predicted values will be calculated.
• MRC SCORE > 1
7. Residual Volume (RVol) ≥20% above predicted value demonstrating evidence of reversibility post bronchodilator of ≥7.5% predicted.

E.4

Principal exclusion criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
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. α1-antitrypsin deficiency: Subjects with known α-1 antitrypsin deficiency as the underlying cause of COPD
4. Other respiratory disorders: Subjects with active tuberculosis or lung cancer as well as clinically significant bronchiectasis, sarcoidosis, pulmonary fibrosis, interstitial lung diseases or other active pulmonary diseases. Pulmonary hypertension from causes other than COPD.
5. Lung resection or transplantation: Subjects with lung volume reduction surgery within the 12 months prior to Screening or having had a lung transplant or pneumonectomy.
6. A moderate/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 corticosteroids (if applicable).
7. Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to screening.
8. Pulmonary Rehabilitation: Patients to be excluded if they have been in the acute phase of pulmonary rehabilitation in the 4 weeks prior to screening
9. Current severe heart failure. Subjects will also be excluded if they have a known ejection fraction of <30%.
10. Abnormal and clinically significant 12-lead ECG
11. Other systemic inflammatory conditions associated with chronic inflammation in the opinion of the investigator (e.g. rheumatoid arthritis, connective tissue disorders and Inflammatory Bowel Disease)
12. Other significant diseases / abnormalities: Any life-threatening condition with life expectancy <1 year, other than vascular disease or COPD, that might prevent the subject from completing the study.
13. Coronary Artery Bypass Grafting (CABG) in the 6 months prior to screening.
14. Myocardial infarction, cerebrovascular event or coronary artery intervention other than CABG in the 1 month prior to screening. Inclusion of these patients with events over 1 month prior to screening will be based on physician’s judgment.
15. History of malignancy within the past 5 years, other than non-melanoma skin cancer.
16. End stage chronic renal disease: Subjects will be excluded if on renal replacement therapy (hemodialysis or peritoneal).
17. 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.
18. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
19. Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen should not be initiated during the trial.
20. 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.
21. Additional medication: Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
22. Use of the following medications is not permitted within the following timeframes (Please refer to study Protocol for the table timeframe, page 22).

E.5 End points

E.5.1

Primary end point(s)

Change in Right Ventricular End Diastolic Volume Index (RVEDVI) from baseline at the end of each treatment period.

E.5.1.1

Timepoint(s) of evaluation of this end point

At the end of each 7 day treatment period

E.5.2

Secondary end point(s)

• Change in Left Atrial (LA) volumes and function from baseline at the end of each treatment period
• Change in Right Ventricular (RV) end systolic volume index (RVESVI) from baseline at the end of each treatment period
• Change in LV end diastolic and end systolic index (EDVI or ESVI) and Ejection Fraction from baseline at the end of each treatment period
• Change in LV mass index (LVMI) from baseline at the end of each treatment period
• Change in LV and RV strain from baseline at the end of each treatment period
• Change in CMR pulse wave velocity (m/s) (pulmonary and aortic) from baseline at the end of each treatment period
• Change in Vicorder PWV (m/s) from baseline at the end of each treatment period
• Change in aortic distensibility from baseline at the end of each treatment period
• Change Pulmonary artery measures from baseline at the end of each treatment period

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of each 7 day treatment period

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last Subject’s Last Visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The investigator is responsible for ensuring that consideration has been given to the post-study care of the patient’s medical condition whether or not GSK is providing specific post study treatment.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-10-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-08-08

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