Trial Outcomes & Findings for A 24-Week Study to Evaluate the Safety and Efficacy of ADVAIR DISKUS® Inhaler 250/50mcg Plus SPIRIVA HANDIHALER® Inhaler Versus SPIRIVA HANDIHALER® Inhaler Plus Placebo DISKUS® Inhaler in Subjects With Chronic Obstructive Pulmonary Disease (COPD). (NCT NCT00784550)

Last Updated: 2016-11-23

Results Overview

Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose FEV1 for each participant) value minus the baseline value. FEV1 is defined as the amount of air expelled from the lungs in one second after a full inspiration and is a measure of pulmonary function.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

342 participants

Primary outcome timeframe

Baseline and Endpoint (defined as the last recorded measure [taken up to Week 24] of AM pre-dose FEV1 for each participant)

Results posted on

2016-11-23

Participant Flow

Participant milestones

Participant milestones
Measure	FSC + Tio Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Overall Study STARTED	173	169
Overall Study COMPLETED	137	127
Overall Study NOT COMPLETED	36	42

Reasons for withdrawal

Reasons for withdrawal
Measure	FSC + Tio Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Overall Study Adverse Event	12	10
Overall Study Lack of Efficacy	0	1
Overall Study Protocol Violation	10	10
Overall Study Lost to Follow-up	8	5
Overall Study Physician Decision	2	3
Overall Study Withdrawal by Subject	4	13

Baseline Characteristics

A 24-Week Study to Evaluate the Safety and Efficacy of ADVAIR DISKUS® Inhaler 250/50mcg Plus SPIRIVA HANDIHALER® Inhaler Versus SPIRIVA HANDIHALER® Inhaler Plus Placebo DISKUS® Inhaler in Subjects With Chronic Obstructive Pulmonary Disease (COPD).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FSC + Tio n=173 Participants Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 Participants Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID	Total n=342 Participants Total of all reporting groups
Age, Continuous	61.3 Years STANDARD_DEVIATION 8.56 • n=5 Participants	61.0 Years STANDARD_DEVIATION 9.41 • n=7 Participants	61.2 Years STANDARD_DEVIATION 8.98 • n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	96 Participants n=7 Participants	182 Participants n=5 Participants
Sex: Female, Male Male	87 Participants n=5 Participants	73 Participants n=7 Participants	160 Participants n=5 Participants
Race/Ethnicity, Customized White	165 participants n=5 Participants	162 participants n=7 Participants	327 participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Endpoint (defined as the last recorded measure [taken up to Week 24] of AM pre-dose FEV1 for each participant)

Population: Intent-to-Treat (ITT) Population: all participants randomized to study drug

Outcome measures

Outcome measures
Measure	FSC + Tio n=173 Participants Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 Participants Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Expiratory Volume in One Second (FEV1) at Endpoint	101 milliliters (ml) Standard Error 21.8	-16 milliliters (ml) Standard Error 20.4

SECONDARY outcome

Timeframe: Baseline and Endpoint (defined as the last recorded measure [taken up to Week 24] of 2 hour post-dose FEV1 for each participant)

Population: ITT Population

Change from baseline was calculated as the Endpoint (defined as the last recorded measure of 2 hour post-dose FEV1 for each participant) value minus the baseline value. FEV1 is defined as the amount of air expelled from the lungs in one second after a full inspiration and is a measure of pulmonary function.

Outcome measures

Outcome measures
Measure	FSC + Tio n=173 Participants Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 Participants Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Mean Change From Baseline in 2 Hour Post-dose FEV1 at Endpoint	233 ml Standard Error 23.1	77 ml Standard Error 20.6

SECONDARY outcome

Timeframe: Baseline and Endpoint (defined as the last recorded measure [up to Week 24] of AM pre-dose FVC for each participant)

Population: ITT Population

Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose FVC fore each participant) value minus the baseline value. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration.

Outcome measures

Outcome measures
Measure	FSC + Tio n=173 Participants Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 Participants Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-dose Forced Vital Capacity (FVC) at Endpoint	95 ml Standard Error 32.7	-28 ml Standard Error 30.6

SECONDARY outcome

Timeframe: Baseline and Endpoint (defined as the last recorded measure of 2 hour post-dose FVC [up to Week 24] for each participant)

Population: ITT Population

Change from baseline was calculated as the Endpoint (defined as the last recorded measure of 2 hour post-dose FVC for each participant) value minus the baseline value. FVC is defined as the amount of air that can forcibly be blown out after a full inspiration (FVC).

Outcome measures

Outcome measures
Measure	FSC + Tio n=173 Participants Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 Participants Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Mean Change From Baseline in 2 Hour Post-dose FVC at Endpoint	265 ml Standard Error 35.9	87 ml Standard Error 31.2

SECONDARY outcome

Timeframe: Baseline and Endpoint (defined as the last recorded measure of AM pre-dose IC [up to Week 24] for each participant)

Population: ITT Population

Change from baseline was calculated as the Endpoint (defined as the last recorded measure of AM pre-dose IC for each participant) value minus the baseline value. IC is defined as the amount of air that can be inhaled after a normal expiration. IC is a measure of pulmonary function.

Outcome measures

Outcome measures
Measure	FSC + Tio n=173 Participants Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 Participants Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Mean Change From Baseline in AM (Morning, Approximately 6-9 AM) Pre-Dose Inspiratory Capacity (IC) at Endpoint	107 ml Standard Error 28.4	-8 ml Standard Error 28.1

SECONDARY outcome

Timeframe: Baseline and Endpoint (defined as the last recorded score [up to Week 24 or the early withdrawal visit] on each of the questions on this questionnaire)

Population: ITT Population

The CRQ-SAS measures 4 domains of functioning of participants with COPD: mastery (amount of control the participant feels he/she has over COPD symptoms); fatigue (how tired the participant feels); emotional function (how anxious/depressed the participant feels); and dyspnea (how short of breath the participant feels during physical activities). Each domain is measured on a scale of 1-7 (1=maximum impairment; 7=no impairment). Each domain score is calculated separately.

Outcome measures

Outcome measures
Measure	FSC + Tio n=173 Participants Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 Participants Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint Mastery	0.28 points on a scale Standard Error 0.078	0.04 points on a scale Standard Error 0.090
Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint Fatigue	0.23 points on a scale Standard Error 0.094	0.17 points on a scale Standard Error 0.091
Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint Emotional Function	0.24 points on a scale Standard Error 0.072	0.16 points on a scale Standard Error 0.073
Mean Change From Baseline in Scores on the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) at Endpoint Dyspnea	0.21 points on a scale Standard Error 0.091	0.19 points on a scale Standard Error 0.091

Adverse Events

FSC + Tio

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Tiotropium

Serious events: 13 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	FSC + Tio n=173 participants at risk Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 participants at risk Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	13.9% 24/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	14.2% 24/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Nervous system disorders Headache	6.4% 11/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	5.3% 9/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	FSC + Tio n=173 participants at risk Open-label tiotropium (Tio) 18 micrograms (mcg) once-daily (QD) plus double-blind Fluticasone Propionate/Salmeterol Combination (FSC) 250/50 mcg twice daily (BID)	Tiotropium n=169 participants at risk Open-label Tio 18 mcg QD plus double-blind matching placebo DISKUS BID
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	3.0% 5/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Gastrointestinal disorders Ileus	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Gastrointestinal disorders Esophagitis	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Infections and infestations Gastric infection	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Infections and infestations Gastroenteritis	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.00% 0/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Infections and infestations Gastroenteritis viral	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma recurrent	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.00% 0/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm malignant	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
General disorders Non-cardiac chest pain	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Injury, poisoning and procedural complications Spinal compression fracture	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.00% 0/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Injury, poisoning and procedural complications Splenic rupture	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Metabolism and nutrition disorders Hypokalemia	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Nervous system disorders Cerebrovascular accident	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Nervous system disorders Transient ischemic attack	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Renal and urinary disorders Calculus ureteric	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.00% 0/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Renal and urinary disorders Urinary retention	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.00% 0/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Injury, poisoning and procedural complications Finger amputation	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Injury, poisoning and procedural complications Shoulder operation	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Vascular disorders Aortic aneurysm	0.58% 1/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.00% 0/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Vascular disorders Hemorrhage	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Blood and lymphatic system disorders Hemolytic anemia	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.
Cardiac disorders Coronary artery disease	0.00% 0/173 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.	0.59% 1/169 The serious adverse events of finger amputation and shoulder amputation were actually coded to the system organ class of surgical and medical procedures.