Study to evaluate the effect of fluticasone furoate/vilanterol on survival
in subjects with chronic obstructive pulmonary disease who have history of cardiovascular disease.
Scientific Title of Study
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.
PAREXEL International Clinical Research Private Limited
Address
Plot # 180, 3rd Floor, MFAR Silverline Tech Park, EPIP II Phase, Whitefield, Bangalore – 560066, Karnataka, India
Bangalore KARNATAKA 560066 India
Phone
08040659311
Fax
08040956536-7-8
Email
Annappa.Kamath@parexel.com
Source of Monetary or Material Support
GlaxoSmithKline, GlaxoSmithKline Research and Development Limited
1-3 Iron Bridge Road,
Stockley Park West,
Uxbridge, Middlesex,
UB11 1BU, United Kingdom
Primary Sponsor
Name
GlaxoSmithKline
Address
GlaxoSmithKline Research and Development Limited,
1-3 Iron Bridge Road,
Stockley Park West,
Uxbridge, Middlesex,
UB11 1BU, United Kingdom
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
PAREXEL International Clinical Research Private Limited
Plot # 180, 3rd Floor,
MFAR Silverline Techpark,
EPIP II Phase, Whitefield,
Bangalore - 560 066,
Karnataka, INDIA.
Austria Argentina Australia Belarus Bosnia and Herzegovina Bulgaria Canada Chile China Colombia Croatia Czech Republic Democratic People's Republic of Korea Denmark France Georgia Germany Greece Hungary India Indonesia Israel Italy Japan Latvia Mexico Pakistan Peru Philippines Poland Romania Russian Federation Serbia Slovakia South Africa Spain Taiwan Thailand The former Yugoslav Republic of Macedonia Turkey Ukraine United Kingdom United States of America Viet Nam Belgium Malaysia Netherlands
Survey # 15, Marigold Complex, Behind Gold Adlabs, Kalyaninagar, Pune - 411014, Maharashtra, India. Pune MAHARASHTRA
09823018373
ssalvi@crfindia.com
Dr Ashish Shankarrao Deshmukh
CIGMA Institute of Medical Sciences PVT Ltd
Department of Respiratory Care, No. 3, Raghuveer Nagar, Opp. SFS High School, Jalna Road, Aurangabad - 431001, Maharashtra, India. Aurangabad MAHARASHTRA
09657715067
drdeshmukhas@rediffmail.com
Dr Raj Gautam Bhagat
Dr. Bhagats Allergy - Asthma Clinic and respiratory Care Centre
Dr. Bhagat Allergy-Asthma Clinic and Respiratory Care Centre,
Pathik, Dashaporwad Society, Gazarwala Flat’s Lane,
Behind Paldi Bus Stand, Ahmedabad - 380007, Gujarat, India Ahmadabad GUJARAT
07926574746
rajres@hotmail.com
Dr Bhickchand Kapurchand Mutha
Dr. Mutha Hospital
P -69, MIDC Satpur, Trimbak Road, Nashik - 422007, Maharasthra, India. Nashik MAHARASHTRA
09373905839
drbkmutha@yahoo.co.in
Dr Deepali Kamdar
Jaydeep Hospital
B/403,404, Rudra Arcade, Helmet Cross Roads, Near Mayflower Hospital, Memnagar, Ahmedabad - 380052, Gujarat, India Ahmadabad GUJARAT
09825038282
drdjkamdar_27@yahoo.com
Dr Vinod Kumar Pavithran
KVM Hospital
Post Box No: 30, Cherthala, Alappuzha - 688524, Kerala, India Alappuzha KERALA
09782812228
drvinodmd@gmail.com
Dr Raghava Sarma Veera Polavarapu
Lalitha Super specialities Hospital Pvt. Ltd.
Department of Cardiology, Kothapet, Guntur - 522001, Andhra Pradesh, India Guntur ANDHRA PRADESH
09440808620
drpvr.lssh@gmail.com
Dr Ravindra Sarnaik
Leela Mores Chest Clinic
Leela Mores Chest Clinic & Critical Care Unit, # 57 North Avenue, Dhantoli, Nagpur - 440012, Maharashtra, India Nagpur MAHARASHTRA
09823037684
dr.rsarnaik@yahoo.com
Dr Uma Maheshwari Krishnaswamy
M S Ramaiah Memorial Hospital
Department of Chest Medicine, New BEL Road, MSRIT Post, Bangalore - 560054, Karnataka, India. Bangalore KARNATAKA
09483702412 08023605190 umamohan99@gmail.com
Dr Paul Thomas
Madonna Hospital and Research Centre
Ernakulam District, Angamaly - 683572, Kerala, India. Ernakulam KERALA
09388604125
madonna.research@gmail.com
Dr Balkrishna Onkar Tayade
NKP Salve Institute of Medical Sciences & Lata Mangeshkar Hospital
Department of Chest Medicine, Digdoh Hills, Hingna Road, Nagpur - 440019, Maharasthra, India. Nagpur MAHARASHTRA
09422118730
botayade123@gmail.com
Dr Rahil Farhid
Sahar Hospital
6, Nabibullah Road, Near Playway School, Lucknow - 226018, Uttar Pradesh, India Lucknow UTTAR PRADESH
27-28, Vidhut Nagar – A, Ajmer Road, Jaipur - 302006, Rajasthan, India Jaipur RAJASTHAN
09829058627
drchouhan22@gmail.com
Dr George Albert DSouza
St Johns Medical College and Hospital
Department of Pulmonary Medicine, New Oncology Building, 3rd Floor, PFT (LAB), St. Johns Medical College & Hospital, Sarjapur Road, Bangalore - 560034, Karnataka, India. Bangalore KARNATAKA
080-22065353
dsouza.ga1975@gmail.com
Dr Vivek Gupta
Suretech Hospital & Research Centre Ltd
13 A , Banerjee Marg, Dhantoli, Nagpur - 440012, Maharashtra, India Nagpur MAHARASHTRA
09373115548
vivekurvashi@yahoo.co.in
Dr Judo Joseph Vachaparambil
Westfort Hi-tech hospital Pvt. Ltd.
Department of Pulomonology, Post Box No. 930, Punkunnam, Trisshur - 680002, Kerala, India Thrissur KERALA
Moderate Chronic Obstructive Pulmonary Disease and a history of or at increased risk for cardiovascular disease,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Fluticasone Furoate Inhalation powder 100mcg
Fluticasone Furoate Inhalation powder 100mcg Once daily dose administered via the Novel Dry Powder Inhaler for a duration of 15 to 44 months
Intervention
Fluticasone Furoate Inhalation powder 100mcg and Vilanterol Inhalation powder 25mcg
Fluticasone Furoate 100mcg and Vilanterol 25mcg Inhalation Powder administered once daily dose via the Novel Dry Powder Inhaler for a duration of 15 to 44 months
Comparator Agent
Vilanterol Inhalation powder 25mcg
Vilanterol Inhalation powder 25mcg Once daily dose administered via the Novel Dry Powder Inhaler for a duration of 15 to 44 months
Inclusion Criteria
Age From
40.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
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: > or equal to 40 years and < or equal to 80 years of age at Screening (Visit 1).
5.Tobacco use: Subjects with a current or prior history of > or equal to 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 forced expiratory volume in 1 second (FEV1)/(forced vital capacity)FVC ratio of < or equal to 0.70 at Screening (Visit 1).
Subjects with a measured post-albuterol/salbutamol FEV1 > or equal to 50 and < or equal to 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 a metered dose inhaler (MDI )with a valved-holding chamber. The FEV1/FVC ratio and FEV1 percent predicted values will be calculated.
7.Symptoms of COPD: Subjects must score 2 or higher on the modified Medical Research Council Dyspnea scale (Visit 1)
8.Cardiovascular disease:
For patients > or equal to 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 vascular disease (PVD) Previous stroke Previous MI Diabetes mellitus with target organ disease OR
For patients > or equal to 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
ExclusionCriteria
Details
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.alpha 1-antitrypsin deficiency: Subjects with known alpha-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 subjects 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. < or equal to 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): Medication No use within the following time intervals prior to Screening or thereafter at any time during the study (unless otherwise specified) Inhaled Long acting beta-agonists (LABA) 48 hours ICS/LABA combination products 48 hours Inhaled corticosteroids 48 hours Tiotropium 1 week Systemic, Oral, parenteral, intra-articular corticosteroids 30 days (oral and systemic corticosteroids may be used to treat COPD exacerbations during the study) Cytochrome P450 3A4 strong inhibitors including but not limited to antiretrovirals (protease inhibitors) (e.g.Indinavir, Nelfinavir, Ritonavir, Saquinavir); Imidazole and Triazole anti-fungals (e.g. Ketaconazole, Itraconazole); Clarithromycin, Telithromycin, Amiodarone, and Nefazodone 6 weeks Grapefruit is allowed up to Visit 1, then limited to no more than one glass of grapefruit juice (250 mL/ 8 ounces) or one grapefruit per day Any other investigational drug 30 days or 5 half lives whichever is longer.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Survival in subjects with moderate COPD (≥50% and ≤70 % predicted Forced Expiratory Volume in One Second - FEV1) with a
history of, or at increased risk for cardiovascular disease
Time to death from any cause
Secondary Outcome
Outcome
TimePoints
The rate of decline in Forced Expiratory Volume in One Second (FEV1) as the effect of Fluticasone Furoate and Vilanterol compared with placebo
Rate of decline in Forced Expiratory Volume in One Second (FEV1)
A cardiovascular composite endpoint comprised of on-treatment Cardiovascular death, myocardial infarction, stroke, unstable angina and TIA on the the effect of Fluticasone Furoate/Vilanterol compared with placebo
Total Sample Size="16000" Sample Size from India="396" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
This is a randomized, double-blind, parallel-group, multi-center, placebo-controlled study to evaluate the long term efficacy and safety of Fluticasone furoate and Vilanterol Inhalation powder 100/25mcg Once Daily, Fluticasone furoate Inhalation powder 100mcg Once Daily and Vilanterol Inhalation powder 25mcg Once Daily when administered via the Novel Dry Powder Inhaler. Once daily dosing will occur in the morning (with the exception of the first treatment visit).
The target enrolment is approximately 16,000 randomized subjects at approximately 1600 study centers globally. Based on current assumptions of the event rate, the total duration of subject participation will be approximately between 15 and 44 months, consisting of a 4-10 day run-in period, variable treatment period and 1-week follow-up period.