Study Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Inhalation Powder (FF/VI) Compared With Vilanterol Inhalation Powder (VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02105974
• Collaborator: (none)
• Enrollment: 1,621
• Locations: 238
• Arms: 2
• Actual Duration (Months): 15
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This is a Phase IIIa, multicenter, randomized, stratified (reversibility status), double-blind, parallel-group study to evaluate the efficacy and safety of FF/VI 100/25 micrograms (mcg) once daily (QD) compared with VI 25 mcg QD, administered in the morning via the ELLIPTA™ inhaler. The primary objective of this study is to evaluate the contribution on lung function (as measured by trough forced expiratory volume in one second [FEV1]) of FF 100 mcg to the FF/VI 100/25 mcg QD combination by comparison of the latter with VI 25 mcg QD and the safety of FF/VI 100/25 mcg over a 12-week treatment period in subjects with COPD. ELLIPTA™ is a registered trademark of GlaxoSmithKline.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Fluticasone Furoate/Vilanterol; Drug: Vilanterol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1621 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 12-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate/Vilanterol Inhalation Powder (FF/VI) 100/25 mcg Once Daily Compared With Vilanterol Inhalation Powder (VI) 25 mcg Once Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
• Actual Study Start Date: Apr 7, 2014
• Actual Primary Completion Date: Jul 8, 2015
• Actual Study Completion Date: Jul 8, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluticasone Furoate/Vilanterol 100/25 Inhalation Powder Inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA)	Drug: Fluticasone Furoate/Vilanterol; 100 mcg FF micronized drug blended with lactose per blister in one strip and 25 mcg VI micronized drug blended with lactose and magnesium stearate per blister in another strip, administered together by ELLIPTA™ inhaler
Experimental: Vilanterol 25 Inhalation Powder Long-acting beta2-agonist (LABA)	Drug: Vilanterol; 25 mcg of Vilanterol micronized drug (as the 'M' salt triphenylacetate) blended with lactose and magnesium stearate per blister in one strip and lactose in another strip, administered together by ELLIPTA™ inhaler

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline (BL) in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1, on Treatment Day 84 [Baseline to Day 84]

   Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 14, 28, 56 and 84. BL was defined as the mean of the assessments made 30 minutes pre-dose and immediately pre-dose on Treatment Day 1.Trough FEV1 was defined as the mean of the FEV1 values obtained 23 and 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, reversibility status (stratum), BL, region, day, day by BL and day by treatment interactions.

Secondary Outcome Measures

1. Percentage of Rescue-free 24-hour Periods Over the Entire 12-week Treatment Period [BL (Week -1), Week 1 to Week 12]

   Participants were given daily record cards for daily completion from BL (Week -1) through Week 12 (Visit 7) each morning and prior prior to taking study medication (i.e., single-blind and double-blind study medication), supplemental medication (albuterol [salbutamol] if received). Participants recorded number of occasions supplemental albuterol/salbutamol (MDI and/or nebules) or oxitropium bromide (applicable sites in Japan) used over the previous 24 hours and any medical problems that they had experienced and any medication used to treat these medical problems over the previous 24 hours. Rescue-free 24-hour periods are defined as the 24-hour periods in which the rescue medication (albuterol [salbutamol]) was not used. The percentage of 24-hour periods are summarized for the entire treatment period (12 weeks). Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, reversibility status (stratum), baseline (week -1) and region.

2. Time to First On-treatment Occurrence of Moderate or Severe COPD Exacerbation [From the start of double blind study medication until visit 7 (week 12)/Early withdrawal]

   Time to first on-treatment exacerbation was analysed using a Cox proportional hazards model with terms for treatment, reversibility status and percent predicted FEV1 at screening. Exacerbation of COPD is defined by a worsening of symptoms requiring additional treatment. Moderate COPD exacerbation is worsening symptoms of COPD that require treatment with antibiotics and/or systemic corticosteroids. Severe COPD exacerbation is worsening symptoms of COPD that require treatment with in-patient hospitalization. The number of participants with On-Treatment moderate or severe COPD exacerbations are presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type of subject: Outpatient

• Informed consent: Subjects must give their signed and dated written informed consent to participate

• Gender: Male subjects or female subjects. 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.

• Age: >=40 years of age at Screening (Visit 1)

• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society: COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it is also associated with significant systemic consequences.

• Severity of disease: Subjects with a measured post-albuterol (salbutamol) FEV1/ Forced Vital Capacity (FVC) ratio of <=0.70 and FEV1 >=30 to <=70 percent of predicted normal values using Global Lung Function Initiative 2012 reference equations at Screening (Visit 1).

• Tobacco use: Subjects with a current or prior history of >=10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.

• History of COPD exacerbation: A documented history (e.g., medical record verification) of at least one COPD exacerbation in the 12 months prior to Screening (Visit 1) that required either systemic/oral corticosteroids, antibiotics and/or hospitalization.

• Current symptoms of COPD: A Subject Diary combined symptom score (combination of breathlessness, cough, sputum, and night time awakenings requiring treatment with albuterol [salbutamol]) of >=4 on at least 5 of the 7 days immediately preceding Visit 2 (Randomization)

• QTc Criteria: QTc <450 msec or QTc <480 msec for patients with bundle branch block.

Exclusion Criteria:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.

• 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).

• Other respiratory disorders: Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary), primary pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases.

• Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).

• Chest X-ray (or computed tomography [CT] scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Screening (Visit 1) if a chest X-ray or CT scan is not available within 1 year prior to Screening (Visit 1).

• Hospitalization: Subjects who are hospitalized due to poorly controlled COPD that has not resolved at least 4 weeks prior to Screening (Visit 1) and at least 6 weeks following the last dose of systemic corticosteroids.

• Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of any of the following in the 6 weeks prior to Screening (Visit 1): Acute worsening of COPD that is managed by subject with systemic corticosteroids or antibiotics or that requires treatment prescribed by a physician.

• Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Screening (Visit 1).

• COPD exacerbation/lower respiratory tract infection during the Run-In Period: Subjects who experience a moderate/severe COPD exacerbation (As per definition of "COPD Exacerbations and Pneumonia" in protocol) and/or a lower respiratory tract infection (including pneumonia) during the Run-In Period.

• Abnormal, clinically significant laboratory finding: Subjects who have an abnormal clinical significant finding in any liver chemistry test at Screening (Visit 1) or upon repeat prior to randomization.

• Abnormal, clinically significant 12-lead ECG at Screening (Visit 1): Subjects who have an abnormal, clinically significant 12-Lead electrocardiogram (ECG) finding at Screening (Visit 1) or upon repeat prior to randomization.

• Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant and unstable disease such as cardiovascular (e.g., patients requiring implantable cardioverter-defibrillators (ICD), pacemaker requiring a rate set >60 beats per minute (bpm), uncontrolled hypertension, New Your Heart Association Class IV, known left ventricular ejection fraction <30 percent) neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or hematological abnormalities.

• Liver disease: Subjects who have unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Note: Subjects with chronic stable hepatitis B and C are eligible if the subject otherwise meets entry criteria (e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of screening). However, subjects with chronic stable hepatitis B are excluded if significant immunosuppressive or cytotoxic agents are administered, due to risk of hepatitis B reactivation, unless the hepatitis B antivirals are administered as outlined in the Chronic Hepatitis B American Association for the Study of Liver Diseases' (AASLD) Practice Guidelines.

• Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.

• Contraindications: Subjects with a history of allergy or hypersensitivity to any of the study medications (e.g. beta-agonists, corticosteroids) or components of the inhalation powder (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the investigator, contraindicates the subject's participation will also be excluded.

• Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years

• Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol (salbutamol) or their ipratropium bromide for the 4-hour period required prior to spirometry testing at each study visit.

• Additional medication: Use of certain medications such as bronchodilators and corticosteroids for the protocol-specific times prior to Visit 1 (the Investigator will discuss the specific medications)"

• Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen as needed (prn) use (i.e., <=12 hours per day) is not exclusionary.

• Sleep apnea: Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV).

• Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study. Subjects who are in the maintenance phase of a Pulmonary Rehabilitation Program are not excluded.

• Non-Compliance during Run-In Period: Failure to demonstrate adequate compliance defined as completion of Diary Card (completed all diary entries on at least 5 of the last 7 consecutive days), the ability to withhold anti-COPD medications and to keep clinic visit appointments. In addition, subjects must have recorded the Run-In study medication use on at least 5 of the last 7, consecutive days of the Run-In period to continue in the study.

• Potential of non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

• 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.

• Prior use of study medication/other investigational drugs: Subjects who have received an investigational drug within 30 days of entry into this study (Screening), or within 5 drug half-lives of the investigational drug, whichever is longer. Note: Subjects who participated in a previously completed study and/or were excluded/ withdrawn from an ongoing study that included/includes FF/VI and/or VI are eligible to participate in the current study, if they have not received investigational study medication within 30 days of Screening (Visit 1).

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Riverside	California	United States	92506
2	GSK Investigational Site	Sunset	Louisiana	United States	70584
3	GSK Investigational Site	Saint Charles	Missouri	United States	63301
4	GSK Investigational Site	Charlotte	North Carolina	United States	28207
5	GSK Investigational Site	Wilmington	North Carolina	United States	28401
6	GSK Investigational Site	Cincinnati	Ohio	United States	45231
7	GSK Investigational Site	Medford	Oregon	United States	97504
8	GSK Investigational Site	Erie	Pennsylvania	United States	16508
9	GSK Investigational Site	Easley	South Carolina	United States	29640
10	GSK Investigational Site	Gaffney	South Carolina	United States	29340
11	GSK Investigational Site	Greenville	South Carolina	United States	29615
12	GSK Investigational Site	Seneca	South Carolina	United States	29678
13	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
14	GSK Investigational Site	Union	South Carolina	United States	29379
15	GSK Investigational Site	Bristol	Tennessee	United States	37620
16	GSK Investigational Site	Johnson City	Tennessee	United States	37601
17	GSK Investigational Site	Morgantown	West Virginia	United States	26505
18	GSK Investigational Site	Dimitrovgrad		Bulgaria	6400
19	GSK Investigational Site	Pleven		Bulgaria	5800
20	GSK Investigational Site	Plovdiv		Bulgaria	4000
21	GSK Investigational Site	Ruse		Bulgaria	7000
22	GSK Investigational Site	Sofia		Bulgaria	1202
23	GSK Investigational Site	Sofia		Bulgaria	1431
24	GSK Investigational Site	Varna		Bulgaria	9000
25	GSK Investigational Site	Vidin		Bulgaria	3700
26	GSK Investigational Site	Aschaffenburg	Bayern	Germany	63739
27	GSK Investigational Site	Muenchen	Bayern	Germany	80339
28	GSK Investigational Site	Muenchen	Bayern	Germany	80539
29	GSK Investigational Site	Ruedersdorf	Brandenburg	Germany	15562
30	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
31	GSK Investigational Site	Hannover	Niedersachsen	Germany	30159
32	GSK Investigational Site	Hannover	Niedersachsen	Germany	30173
33	GSK Investigational Site	Osnabrueck	Niedersachsen	Germany	49074
34	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45359
35	GSK Investigational Site	Goch	Nordrhein-Westfalen	Germany	47574
36	GSK Investigational Site	Magdeburg	Sachsen-Anhalt	Germany	39112
37	GSK Investigational Site	Delitzsch	Sachsen	Germany	04509
38	GSK Investigational Site	Leipzg	Sachsen	Germany	04109
39	GSK Investigational Site	Leipzig	Sachsen	Germany	04275
40	GSK Investigational Site	Geesthacht	Schleswig-Holstein	Germany	21502
41	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
42	GSK Investigational Site	Berlin		Germany	10367
43	GSK Investigational Site	Berlin		Germany	10717
44	GSK Investigational Site	Berlin		Germany	10787
45	GSK Investigational Site	Berlin		Germany	12203
46	GSK Investigational Site	Aichi		Japan	454-8502
47	GSK Investigational Site	Aichi		Japan	455-8510
48	GSK Investigational Site	Aichi		Japan	457-8511
49	GSK Investigational Site	Aichi		Japan	460-0001
50	GSK Investigational Site	Aichi		Japan	471-8513
51	GSK Investigational Site	Aichi		Japan	489-8642
52	GSK Investigational Site	Chiba		Japan	278-0004
53	GSK Investigational Site	Chiba		Japan	296-8602
54	GSK Investigational Site	Ehime		Japan	791-0281
55	GSK Investigational Site	Fukuoka		Japan	802-0052
56	GSK Investigational Site	Fukuoka		Japan	802-0083
57	GSK Investigational Site	Fukuoka		Japan	811-1394
58	GSK Investigational Site	Fukuoka		Japan	815-8588
59	GSK Investigational Site	Fukuoka		Japan	816-0813
60	GSK Investigational Site	Fukuoka		Japan	820-8505
61	GSK Investigational Site	Fukuoka		Japan	832-0059
62	GSK Investigational Site	Gifu		Japan	500-8523
63	GSK Investigational Site	Gifu		Japan	500-8717
64	GSK Investigational Site	Gifu		Japan	506-8550
65	GSK Investigational Site	Gifu		Japan	509-6134
66	GSK Investigational Site	Gunma		Japan	372-0831
67	GSK Investigational Site	Hiroshima		Japan	722-8503
68	GSK Investigational Site	Hiroshima		Japan	732-0052
69	GSK Investigational Site	Hiroshima		Japan	734-8530
70	GSK Investigational Site	Hiroshima		Japan	735-8585
71	GSK Investigational Site	Hokkaido		Japan	001-0901
72	GSK Investigational Site	Hokkaido		Japan	040-8611
73	GSK Investigational Site	Hokkaido		Japan	053-8506
74	GSK Investigational Site	Hokkaido		Japan	060-0033
75	GSK Investigational Site	Hokkaido		Japan	062-8618
76	GSK Investigational Site	Hokkaido		Japan	063-0005
77	GSK Investigational Site	Hokkaido		Japan	064-0801
78	GSK Investigational Site	Hokkaido		Japan	064-0915
79	GSK Investigational Site	Hokkaido		Japan	070-8644
80	GSK Investigational Site	Hokkaido		Japan	071-8132
81	GSK Investigational Site	Hokkaido		Japan	080-0013
82	GSK Investigational Site	Hokkaido		Japan	080-0805
83	GSK Investigational Site	Hyogo		Japan	650-0047
84	GSK Investigational Site	Hyogo		Japan	664-8540
85	GSK Investigational Site	Hyogo		Japan	672-8064
86	GSK Investigational Site	Hyogo		Japan	675-8611
87	GSK Investigational Site	Hyogo		Japan	678-0239
88	GSK Investigational Site	Ibaraki		Japan	310-0015
89	GSK Investigational Site	Ibaraki		Japan	317-0077
90	GSK Investigational Site	Ibaraki		Japan	319-1113
91	GSK Investigational Site	Ishikawa		Japan	920-8530
92	GSK Investigational Site	Ishikawa		Japan	920-8610
93	GSK Investigational Site	Ishikawa		Japan	920-8650
94	GSK Investigational Site	Ishikawa		Japan	921-8105
95	GSK Investigational Site	Ishikawa		Japan	923-8560
96	GSK Investigational Site	Iwate		Japan	024-8506
97	GSK Investigational Site	Kagawa		Japan	760-0018
98	GSK Investigational Site	Kagawa		Japan	760-8538
99	GSK Investigational Site	Kagawa		Japan	761-8073
100	GSK Investigational Site	Kagawa		Japan	762-8550
101	GSK Investigational Site	Kanagawa		Japan	232-0024
102	GSK Investigational Site	Kanagawa		Japan	232-0066
103	GSK Investigational Site	Kanagawa		Japan	239-0821
104	GSK Investigational Site	Kanagawa		Japan	251-8550
105	GSK Investigational Site	Kanagawa		Japan	254-8502
106	GSK Investigational Site	Kochi		Japan	780-8077
107	GSK Investigational Site	Kochi		Japan	783-8505
108	GSK Investigational Site	Kumamoto		Japan	861-1196
109	GSK Investigational Site	Kumamoto		Japan	862-0954
110	GSK Investigational Site	Kyoto		Japan	601-1495
111	GSK Investigational Site	Kyoto		Japan	601-8206
112	GSK Investigational Site	Kyoto		Japan	607-8062
113	GSK Investigational Site	Kyoto		Japan	612-0026
114	GSK Investigational Site	Kyoto		Japan	615-8087
115	GSK Investigational Site	Mie		Japan	514-1101
116	GSK Investigational Site	Mie		Japan	515-8544
117	GSK Investigational Site	Miyagi		Japan	980-8574
118	GSK Investigational Site	Miyagi		Japan	981-8563
119	GSK Investigational Site	Miyagi		Japan	983-8520
120	GSK Investigational Site	Miyagi		Japan	984-8560
121	GSK Investigational Site	Miyagi		Japan	986-8522
122	GSK Investigational Site	Miyagi		Japan	989-1253
123	GSK Investigational Site	Nagano		Japan	390-0872
124	GSK Investigational Site	Niigata		Japan	950-2085
125	GSK Investigational Site	Oita		Japan	870-0921
126	GSK Investigational Site	Oita		Japan	876-0813
127	GSK Investigational Site	Okayama		Japan	702-8055
128	GSK Investigational Site	Okayama		Japan	711-0921
129	GSK Investigational Site	Okinawa		Japan	901-0243
130	GSK Investigational Site	Okinawa		Japan	901-2121
131	GSK Investigational Site	Okinawa		Japan	901-2132
132	GSK Investigational Site	Okinawa		Japan	904-2143
133	GSK Investigational Site	Okinawa		Japan	904-2293
134	GSK Investigational Site	Osaka		Japan	530-0001
135	GSK Investigational Site	Osaka		Japan	530-8480
136	GSK Investigational Site	Osaka		Japan	533-0024
137	GSK Investigational Site	Osaka		Japan	564-0013
138	GSK Investigational Site	Osaka		Japan	570-8540
139	GSK Investigational Site	Osaka		Japan	573-0153
140	GSK Investigational Site	Osaka		Japan	576-0041
141	GSK Investigational Site	Osaka		Japan	591-8037
142	GSK Investigational Site	Osaka		Japan	591-8555
143	GSK Investigational Site	Osaka		Japan	596-8501
144	GSK Investigational Site	Saitama		Japan	349-1105
145	GSK Investigational Site	Shizuoka		Japan	430-8525
146	GSK Investigational Site	Shizuoka		Japan	434-8511
147	GSK Investigational Site	Tokyo		Japan	103-0027
148	GSK Investigational Site	Tokyo		Japan	103-0028
149	GSK Investigational Site	Tokyo		Japan	104-8560
150	GSK Investigational Site	Tokyo		Japan	134-0083
151	GSK Investigational Site	Tokyo		Japan	140-0011
152	GSK Investigational Site	Tokyo		Japan	140-0013
153	GSK Investigational Site	Tokyo		Japan	153-0051
154	GSK Investigational Site	Tokyo		Japan	158-8531
155	GSK Investigational Site	Tokyo		Japan	171-0014
156	GSK Investigational Site	Tokyo		Japan	187-0002
157	GSK Investigational Site	Tokyo		Japan	190-0014
158	GSK Investigational Site	Tokyo		Japan	194-0023
159	GSK Investigational Site	Tokyo		Japan	198-0042
160	GSK Investigational Site	Tokyo		Japan	204-8522
161	GSK Investigational Site	Toyama		Japan	930-0982
162	GSK Investigational Site	Toyama		Japan	931-8553
163	GSK Investigational Site	Toyama		Japan	937-0042
164	GSK Investigational Site	Toyama		Japan	938-8502
165	GSK Investigational Site	Toyama		Japan	939-8511
166	GSK Investigational Site	Yamaguchi		Japan	755-0241
167	GSK Investigational Site	Bucheon		Korea, Republic of	420-717
168	GSK Investigational Site	Daegu		Korea, Republic of	705-717
169	GSK Investigational Site	Incheon		Korea, Republic of	403-720
170	GSK Investigational Site	Kangwon-do		Korea, Republic of	220-701
171	GSK Investigational Site	Seoul		Korea, Republic of	100-032
172	GSK Investigational Site	Seoul		Korea, Republic of	130-709
173	GSK Investigational Site	Seoul		Korea, Republic of	136-705
174	GSK Investigational Site	Seoul		Korea, Republic of	140-743
175	GSK Investigational Site	Seoul		Korea, Republic of	150-713
176	GSK Investigational Site	Seoul		Korea, Republic of	156-755
177	GSK Investigational Site	Bialystok		Poland	15-044
178	GSK Investigational Site	Gdynia		Poland	81-384
179	GSK Investigational Site	Krakow		Poland	31-011
180	GSK Investigational Site	Krakow		Poland	31-024
181	GSK Investigational Site	Lodz		Poland	90-242
182	GSK Investigational Site	Skierniewice		Poland	96-100
183	GSK Investigational Site	Warszawa		Poland	01-192
184	GSK Investigational Site	Wroclaw		Poland	50-088
185	GSK Investigational Site	Bacau		Romania	600252
186	GSK Investigational Site	Braila		Romania	810003
187	GSK Investigational Site	Brasov		Romania	500118
188	GSK Investigational Site	Cluj Napoca		Romania	400371
189	GSK Investigational Site	Cluj-Napoca		Romania	400371
190	GSK Investigational Site	Comuna Alexandru Cel Bun		Romania	617507
191	GSK Investigational Site	Craiova		Romania	200515
192	GSK Investigational Site	Iasi		Romania	700115
193	GSK Investigational Site	Ploiesti		Romania	100184
194	GSK Investigational Site	Ploiesti		Romania	100379
195	GSK Investigational Site	Suceava		Romania	720284
196	GSK Investigational Site	Chelyabinsk		Russian Federation	454106
197	GSK Investigational Site	Izhevsk		Russian Federation	426063
198	GSK Investigational Site	Kemerovo		Russian Federation	650000
199	GSK Investigational Site	Kemerovo		Russian Federation	650002
200	GSK Investigational Site	Khantymansiysk		Russian Federation	628012
201	GSK Investigational Site	Moscow		Russian Federation	115 280
202	GSK Investigational Site	Moscow		Russian Federation	125315
203	GSK Investigational Site	Novosibirsk		Russian Federation	630089
204	GSK Investigational Site	Novosibirsk		Russian Federation	630099
205	GSK Investigational Site	Novosibirsk		Russian Federation	630102
206	GSK Investigational Site	Saint Petesburg		Russian Federation	195030
207	GSK Investigational Site	Saint-Petersburg		Russian Federation	195271
208	GSK Investigational Site	Saint-Petersburg		Russian Federation	198260
209	GSK Investigational Site	St. Petersburg		Russian Federation	194356
210	GSK Investigational Site	St. Petersburg		Russian Federation	198216
211	GSK Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6014
212	GSK Investigational Site	Welkom	Free State	South Africa	9460
213	GSK Investigational Site	Meyerspark	Gauteng	South Africa	0184
214	GSK Investigational Site	Pretoria	Gauteng	South Africa	0183
215	GSK Investigational Site	Bellville		South Africa	7530
216	GSK Investigational Site	Bloemfontein		South Africa	9301
217	GSK Investigational Site	Cape Town		South Africa	7572
218	GSK Investigational Site	Durban		South Africa	4001
219	GSK Investigational Site	Gatesville		South Africa	7764
220	GSK Investigational Site	Mowbray		South Africa	7700
221	GSK Investigational Site	Tygerberg		South Africa	7505
222	GSK Investigational Site	Keelung		Taiwan	20401
223	GSK Investigational Site	New Taipei City		Taiwan	23148
224	GSK Investigational Site	Taichung		Taiwan	404
225	GSK Investigational Site	Taichung		Taiwan	40705
226	GSK Investigational Site	Taichung		Taiwan	407
227	GSK Investigational Site	Taichung		Taiwan	427
228	GSK Investigational Site	Dnipropetrovsk		Ukraine	49051
229	GSK Investigational Site	Kharkiv		Ukraine	61002
230	GSK Investigational Site	Kharkiv		Ukraine	61035
231	GSK Investigational Site	Kiev		Ukraine	03680
232	GSK Investigational Site	Kremenchug		Ukraine	39617
233	GSK Investigational Site	Kyiv		Ukraine	02232
234	GSK Investigational Site	Kyiv		Ukraine	03038
235	GSK Investigational Site	Kyiv		Ukraine	03049
236	GSK Investigational Site	Mykolayiv		Ukraine	54003
237	GSK Investigational Site	Odesa		Ukraine	65025
238	GSK Investigational Site	Vinnytsia		Ukraine	21029

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02105974
• Other Study ID Numbers: 200820
• First Posted: Apr 7, 2014
• Last Update Posted: Jan 24, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: COPD; Fluticasone Furoate (FF); Vilanterol (VI); Dry Powder Inhaler
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Fluticasone; Xhance

Study Results

Participant Flow

Recruitment Details	Par meeting continuation criteria during the run-in period were randomized (1:1) to receive fluticasone furoate (FF)/vilanterol (VI) or VI. Of the 2423 par screened, 1622 were randomized. 1620 received at least one dose of double-blind study medication and comprised the Intent-to-Treat population.
Pre-assignment Detail	Participants(par) with a history of chronic obstructive pulmonary disease(COPD) meeting eligibility criteria at screening were enrolled in a 2-week, single-blind(placebo) run-in period to obtain baseline use of albuterol(salbutamol), COPD symptom scores and disease stability.

Arm/Group Title	Placebo Run-In	FF/VI 100/25 µg QD	VI 25 µg QD
Arm/Group Description	Participants received placebo once daily (QD) in the morning for 2 weeks. In addition, participants were provided an inhaled short-acting beta2-receptor agonist (SABA), albuterol (salbutamol) (metered dose inhaler [MDI] or nebules), to be used as a rescue medication for relief of chronic obstructive pulmonary disease (COPD) symptoms during the Run-in and Treatment Periods.	Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler [MDI] or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler [MDI] or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Period Title: 2 Week Run-in Period
STARTED	2423	0	0
COMPLETED	1622	0	0
NOT COMPLETED	801	0	0
Period Title: 2 Week Run-in Period
STARTED	0	806	814
Completed the Treatment(Trt) Period	0	764	754
COMPLETED	0	764	756
NOT COMPLETED	0	42	58

Baseline Characteristics

Arm/Group Title	FF/VI 100/25 µg QD	VI 25 µg QD	Total
Arm/Group Description	Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	Total of all reporting groups
Overall Participants	806	814	1620
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.3 (8.58)	65.4 (9.02)	65.3 (8.80)
Sex: Female, Male (Count of Participants)
Female	201 24.9%	189 23.2%	390 24.1%
Male	605 75.1%	625 76.8%	1230 75.9%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage	6 0.7%	10 1.2%	16 1%
Asian - East Asian Heritage	77 9.6%	77 9.5%	154 9.5%
Asian - Japanese Heritage	185 23%	185 22.7%	370 22.8%
White - White/Caucasian/European Heritage	538 66.7%	541 66.5%	1079 66.6%
Mixed Race	0 0%	1 0.1%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline (BL) in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1, on Treatment Day 84
Description	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 14, 28, 56 and 84. BL was defined as the mean of the assessments made 30 minutes pre-dose and immediately pre-dose on Treatment Day 1.Trough FEV1 was defined as the mean of the FEV1 values obtained 23 and 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, reversibility status (stratum), BL, region, day, day by BL and day by treatment interactions.
Time Frame	Baseline to Day 84

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized par. who received at least one dose of study medication. Number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis

Arm/Group Title	FF/VI 100/25 µg QD	VI 25 µg QD
Arm/Group Description	Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Measure Participants	759	749
Least Squares Mean (Standard Error) [Liter]	0.116 (0.0074)	0.082 (0.0075)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FF/VI 100/25 µg QD, VI 25 µg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed Models Analysis
	Comments	Restricted maximum likelihood (REML)-based repeated measures approach (MMRM)
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	0.034
	Confidence Interval	(2-Sided) 95%; 0.014 to 0.055
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Rescue-free 24-hour Periods Over the Entire 12-week Treatment Period
Description	Participants were given daily record cards for daily completion from BL (Week -1) through Week 12 (Visit 7) each morning and prior prior to taking study medication (i.e., single-blind and double-blind study medication), supplemental medication (albuterol [salbutamol] if received). Participants recorded number of occasions supplemental albuterol/salbutamol (MDI and/or nebules) or oxitropium bromide (applicable sites in Japan) used over the previous 24 hours and any medical problems that they had experienced and any medication used to treat these medical problems over the previous 24 hours. Rescue-free 24-hour periods are defined as the 24-hour periods in which the rescue medication (albuterol [salbutamol]) was not used. The percentage of 24-hour periods are summarized for the entire treatment period (12 weeks). Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, reversibility status (stratum), baseline (week -1) and region.
Time Frame	BL (Week -1), Week 1 to Week 12

Outcome Measure Data

Analysis Population Description

ITT Population, all randomized participants who received at least one dose of study medication. Only those participants with at least 1 on treatment rescue medication measurement during the treatment period and without missing covariate information were analyzed.

Arm/Group Title	FF/VI 100/25 µg QD	VI 25 µg QD
Arm/Group Description	Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Measure Participants	801	802
Least Squares Mean (Standard Error) [Percentage of rescue-free periods]	47.03 (1.070)	44.41 (1.069)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FF/VI 100/25 µg QD, VI 25 µg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.084
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	2.62
	Confidence Interval	(2-Sided) 95%; -0.35 to 5.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Time to First On-treatment Occurrence of Moderate or Severe COPD Exacerbation
Description	Time to first on-treatment exacerbation was analysed using a Cox proportional hazards model with terms for treatment, reversibility status and percent predicted FEV1 at screening. Exacerbation of COPD is defined by a worsening of symptoms requiring additional treatment. Moderate COPD exacerbation is worsening symptoms of COPD that require treatment with antibiotics and/or systemic corticosteroids. Severe COPD exacerbation is worsening symptoms of COPD that require treatment with in-patient hospitalization. The number of participants with On-Treatment moderate or severe COPD exacerbations are presented.
Time Frame	From the start of double blind study medication until visit 7 (week 12)/Early withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	FF/VI 100/25 µg QD	VI 25 µg QD
Arm/Group Description	Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.	Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
Measure Participants	806	814
Number [Participants]	69 8.6%	114 14%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FF/VI 100/25 µg QD, VI 25 µg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Nominal p-value
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.43 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of double-blind (DB) study treatment (Visit 2) through the follow up contact (up to 13 weeks).
Adverse Event Reporting Description	On-treatment AE or SAE is defined as an AE with an onset date on or after the start date of DB study medication, but not later than one day after the last dose of DB study medication. AEs are reported for participants of the ITT, comprised of all randomized participants who received at least one dose of study medication during the treatment period
Arm/Group Title	FF/VI 100/25 µg QD		VI 25 µg QD
Arm/Group Description	Participants received fluticasone furoate/vilaterol (FF/VI) 100/25 microgram(µg) inhalation via a dry powder inhaler (DPI) once daily (QD) in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.		Participants received VI 25 µg inhalation QD via a DPI in the morning for 12 weeks. In addition, all participants were provided with albuterol (salbutamol) or oxitropium bromide (applicable sites in Japan) to be used as rescue medication (via metered-dose inhaler (MDI) or nebules) for relief of COPD symptoms during the Run-In and Treatment Periods.
All Cause Mortality
	FF/VI 100/25 µg QD		VI 25 µg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FF/VI 100/25 µg QD		VI 25 µg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/806 (3.3%)		35/814 (4.3%)
Cardiac disorders
Any event	2/806 (0.2%)		3/814 (0.4%)
Myocardial infarction	1/806 (0.1%)		1/814 (0.1%)
Atrial fibrillation	1/806 (0.1%)		0/814 (0%)
Cardiac failure	0/806 (0%)		1/814 (0.1%)
Cardiac failure congestive	0/806 (0%)		1/814 (0.1%)
Eye disorders
Any event	2/806 (0.2%)		0/814 (0%)
Cataract	2/806 (0.2%)		0/814 (0%)
Gastrointestinal disorders
Any event	1/806 (0.1%)		1/814 (0.1%)
Gastric ulcer	1/806 (0.1%)		0/814 (0%)
Large intestine polyp	0/806 (0%)		1/814 (0.1%)
Hepatobiliary disorders
Any event	0/806 (0%)		1/814 (0.1%)
Cholecystitis acute	0/806 (0%)		1/814 (0.1%)
Infections and infestations
Any event	6/806 (0.7%)		7/814 (0.9%)
Pneumonia	2/806 (0.2%)		4/814 (0.5%)
Appendicitis	1/806 (0.1%)		0/814 (0%)
Bronchitis	0/806 (0%)		1/814 (0.1%)
Cellulitis	1/806 (0.1%)		0/814 (0%)
Epididymitis	0/806 (0%)		1/814 (0.1%)
Hepatitis B	0/806 (0%)		1/814 (0.1%)
Lower respiratory tract infection	1/806 (0.1%)		0/814 (0%)
Pneumonia bacterial	1/806 (0.1%)		0/814 (0%)
Injury, poisoning and procedural complications
Any event	1/806 (0.1%)		3/814 (0.4%)
Contusion	1/806 (0.1%)		0/814 (0%)
Femoral neck fracture	0/806 (0%)		1/814 (0.1%)
Femur fracture	0/806 (0%)		1/814 (0.1%)
Humerus fracture	0/806 (0%)		1/814 (0.1%)
Pelvic fracture	0/806 (0%)		1/814 (0.1%)
Investigations
Any event	0/806 (0%)		2/814 (0.2%)
Blood pressure increased	0/806 (0%)		1/814 (0.1%)
Hepatic enzyme increased	0/806 (0%)		1/814 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Any event	4/806 (0.5%)		4/814 (0.5%)
Pancreatic carcinoma	1/806 (0.1%)		1/814 (0.1%)
Adenocarcinoma pancreas	0/806 (0%)		1/814 (0.1%)
Breast cancer	0/806 (0%)		1/814 (0.1%)
Colon adenoma	1/806 (0.1%)		0/814 (0%)
Hepatic cancer	1/806 (0.1%)		0/814 (0%)
Lung neoplasm malignant	1/806 (0.1%)		0/814 (0%)
Urethral adenoma	0/806 (0%)		1/814 (0.1%)
Nervous system disorders
Any event	2/806 (0.2%)		1/814 (0.1%)
Cerebral infarction	0/806 (0%)		1/814 (0.1%)
Cerebrovascular accident	1/806 (0.1%)		0/814 (0%)
Transient ischaemic attack	1/806 (0.1%)		0/814 (0%)
Psychiatric disorders
Any event	1/806 (0.1%)		0/814 (0%)
Bipolar disorder	1/806 (0.1%)		0/814 (0%)
Reproductive system and breast disorders
Any event	2/806 (0.2%)		0/814 (0%)
Benign prostatic hyperplasia	2/806 (0.2%)		0/814 (0%)
Respiratory, thoracic and mediastinal disorders
Any event	10/806 (1.2%)		19/814 (2.3%)
Chronic obstructive pulmonary disease	10/806 (1.2%)		17/814 (2.1%)
Chronic respiratory failure	1/806 (0.1%)		0/814 (0%)
Epistaxis	0/806 (0%)		1/814 (0.1%)
Pneumonia aspiration	0/806 (0%)		1/814 (0.1%)
Pneumothorax	0/806 (0%)		1/814 (0.1%)
Pulmonary embolism	1/806 (0.1%)		0/814 (0%)
Vascular disorders
Any event	0/806 (0%)		1/814 (0.1%)
Aortic dissection	0/806 (0%)		1/814 (0.1%)
Other (Not Including Serious) Adverse Events
	FF/VI 100/25 µg QD		VI 25 µg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/806 (8.9%)		64/814 (7.9%)
Infections and infestations
Nasopharyngitis	49/806 (6.1%)		48/814 (5.9%)
Nervous system disorders
Headache	29/806 (3.6%)		19/814 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.