Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The purpose of this study is to assess the control of COPD using a symptom and exacerbation risk based treatment strategy based on GOLD 2011. This study is conducted in Japanese subjects with COPD and assess whether the GOLD 2011 strategy is effective in medical practice in Japan.
Detailed description
PROTOCOL SUMMARY Rationale Both ADOAIR and tiotropium bromide ( hereinafter tiotropium）are now well established, effective treatments for COPD and are frequently co-prescribed (hereinafter TRIPLE therapy). The addition of ADOAIR to tiotropium improves lung function and quality of life and may further reduce exacerbations. GOLD 2011 thus recommends TRIPLE therapy as the second choice of COPD treatment strategy. However, the criteria for switching from each individual treatment to TRIPLE therapy are not clearly shown so far. This study will be conducted in Japanese subjects with COPD and will assess whether the GOLD 2011 strategy is effective in medical practice in Japan. Objective(s) The objective of the study is to assess the control of COPD using a symptom and exacerbation risk based treatment strategy based on GOLD 2011. Study Design Multicenter, randomized, double-dummy, 24-weeks, observational study Study Endpoints/Assessments Primary * Proportion of patients who were able to remain on the randomized therapy Secondary * Proportion of patients who switched to TRIPLE therapy * Proportion of patients who controlled by TRIPLE therapy * Proportion of patients controlled by randomized therapy plus TRIPLE therapy * Time to switching to TRIPLE therapy * Time to first exacerbation * Proportion of diagnosed exacerbation confirmed by Daily Record Card * Proportion of exacerbations detected by Daily Record Card not diagnosed * CAT score change * Change in FEV1 * Use of relief medication * Proportion of patients who decreased treatment from TRIPLE therapy * Proportion of patients who required additional treatment to TRIPLE therapy * Proportion of patients who dropped out * Patients' judgment of treatment efficacy * Physician's judgment of treatment efficacy Safety * Adverse event reporting * Exacerbations of COPD
Interventions
DRUGfluticasone propionate/salmeterol 50/250mcg
Active, 50/250mcg, Twice daily (morning and evening)
DRUGfluticasone propionate/salmeterol placebo
Placebo, Twice daily (morning and evening)
Active, 18mcg, Once daily(morning)
DRUGtiotropium bromide placebo
Placebo, Once daily(morning)
DRUGfluticasone propionate/salmeterol 50/250mcg and tiotropium 18mcg
Active. The randomized treatment may be switched to TRIPLE therapy when COPD symptoms are uncontrolled or the subject is not satisfied with the randomized treatment at each scheduled or unscheduled visit.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 40 - 80 years inclusive 2. Has an established clinical history of COPD (defined as per the GOLD definition) 3. The subject achieves a grade of ≥1 on mMRC at Visit 1 4. A signed and dated written informed consent is obtained from the subject prior to study participation 5. The subject has a post-bronchodilator FEV1 of ≥ 30% to ≤ 80% of predicted normal 6. The subject has a post-bronchodilator FEV1 / FVC ratio \< 70% 7. The subject is a current or ex-smoker with a smoking history of \> 10 pack-years Ex-smokers are required to have stopped smoking for at least 6 months prior to visit 1. Ex-smokers who stopped smoking less than 6 months ago will be defined as current smokers. 8. QTc \< 450 msec at Visit 1; or for patients with bundle branch block QTc should be \< 480 msec. (QTc(F) \< 450 msec, or \< 480 msec in subjects with right bundle branch block, should be confirmed by the mean of three readings or one reading) 9. ALT \< 2 x ULN and bilirubin/ALP ≤ 1.5 x ULN (\> 35% direct bilirubin) 10. A female is eligible to enter this study if she is: i) of non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal), or ii) of child-bearing potential, but has a negative urinary pregnancy test at screening and agrees to take contraceptive precautions (including abstinence) which are adequate to prevent pregnancy during the study iii) not a nursing mother
Exclusion criteria
1. Has a predominant asthma (comorbid asthma is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Were Able to Remain on the Randomized Treatment | 24 weeks | The randomized treatment could be switched to TRIPLE therapy in the case that chronic obstructive pulmonary disease (COPD) is not controlled by the randomized treatment. Participants on TRIPLE therapy received SAL/FLU 50/250 µg BID plus TIO 18 µg QD together. The percentage of participants who were able to remain on the randomized treatment was calculated by the following formula: 100 minus percentage of participants who switched over to TRIPLE therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Managed by TRIPLE Therapy | 24 weeks | Percentage of participants managed by TRIPLE therapy was calculated as \[(number of participants who switched to TRIPLE therapy) - (number of participants who stepped down)/ number of evaluable population\]\*100 |
| Continuation Percentage of Participants Managed by Randomized Treatment Plus TRIPLE Therapy | 24 weeks | The randomized treatment could be switched to TRIPLE therapy in the case that chronic obstructive pulmonary disease (COPD) was not controlled by the randomized treatment. Participants on TRIPLE therapy received SAL/FLU 50/250 µg BID plus TIO 18 µg QD together. Continuation TRIPLE proportion is defined as \[(number of subjects who switched to TRIPLE) - (number of subjects who stepped down)/ number of evaluable population\]\*100. Randomised treatment continuation proportion is calculated by a formula: (100 - switch proportion). |
| Time to First Switching to TRIPLE Therapy | 24 weeks | The day of first switch to TRIPLE therapy (SAL/FLU 50/250 µg BID+TIO 18 µg QD) for the first switching participant in each arm. |
| Time to First Exacerbation by Physician's Diagnosis | 24 weeks | The day of detection of first exacerbation in any participant in each arm as diagnosed by physician. Exacerbation is defined primarily by physician's judgment. Date of randomisation will be start point and timing of exacerbation (first exacerbation if there are more than one) will be event. For subjects without exacerbation, last day of study or follow up period is regarded as censor. |
| Time to First Exacerbation by EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) | 24 weeks | The EXAcerbations of Chronic pulmonary disease Tool (EXACT) is a 14-item patient-reported outcome (PRO) daily diary used to quantify and measure exacerbations of chronic obstructive pulmonary disease (COPD). Reported as units on a 0 \[best health status\] to 100 \[worst possible status\] scale). The day of detection of first exacerbation in any participant in each arm by EXACT. |
| EXACT Total Score. | Baseline and up to 24 weeks | EXACT is a 14-item patient questionnaire used as a measure of respiratory symptoms (reported as units on a 0 \[best health status\] to 100 \[worst possible status\] scale). Scores were assessed at Baseline, Week 1-4, Week 5-8, Week 9-12, Week 13-16, Week 17-20 and Week 21-24. Daily EXACT total score is obtained as total score of 14 items from diary. Daily E-RS total score as 11 items and Daily E-RS subscale scores are subset of E-RS total score. Mean EXACT total score is mean value of daily EXACT total score within subject by every 4 weeks(Week1-4, Week5-8, Week9-12, Week13-16, Week17-20, Week21-24). Same calculation of mean values are applied to E-RS total and E-RS subscale scores. |
| EXACT Respiratory Symptoms (E-RS) Total Score | Baseline and up to 24 weeks | The E-RS total score is an 11-item patient questionnaire, which provides information specific to respiratory symptoms-severity of respiratory symptoms overall and severity of breathlessness, cough and sputum, and chest symptoms. Scores were assessed at Baseline, Week 1-4, Week 5-8, Week 9-12, Week 13-16, Week 17-20 and at Week 21-24. Daily EXACT total score is obtained as total score of 14 items from diary. Daily E-RS total score as 11 items and Daily E-RS subscale scores are subset of E-RS total score. Mean EXACT total score is mean value of daily EXACT total score within subject by every 4 weeks(Week1-4, Week5-8, Week9-12, Week13-16, Week17-20, Week21-24). Same calculation of mean values are applied to E-RS total and E-RS subscale scores. Scores range from 0-100, high value in score indicate worse outcome. |
| E-RS Subscale Score | 24 weeks | The E-RS total score is an 11-item patient questionnaire, which provides information specific to respiratory symptoms-severity of respiratory symptoms overall and severity of breathlessness, cough and sputum, and chest symptoms. The E-RS subscale scores for respiratory symptoms (RS)-breathlessness (RS-BRL), RS-cough and sputum (RS-CSP), and RS-chest symptoms (RS-CSY) are presented. Scores were assessed at Baseline, Week 1-4, Week 5-8, Week 9-12, Week 13-16, Week 17-20 and at Week 21-24. Daily EXACT total score is obtained as total score of 14 items from diary. Daily E-RS total score as 11 items and Daily E-RS subscale scores are subset of E-RS total score. Mean EXACT total score is mean value of daily EXACT total score within subject by every 4 weeks(Week1-4, Week5-8, Week9-12, Week13-16, Week17-20, Week21-24). Same calculation of mean values are applied to E-RS total and E-RS subscale scores. RS total scores range from 0 to 40, high value in score indicate worse outcome. |
| Comparison of Number of Exacerbations Between Two Detection Methods: EXACT and Physician Diagnosis | 24 weeks | The comparison of number of exacerbation between two detection methods EXACT and physician diagnosis: number of exacerbations detected by EXACT and number of exacerbations judged by physician. |
| Percentage of Participants Who Switched to TRIPLE Therapy | 24 weeks | Switched to TRIPLE therapy is defined as: 1. Date of switch: when SAL/FLU or TIO was administered additionally to randomised treatment. 2. Date of randomisation was a start point and timing of switching (first switch if there are more than once) to TRIPLE was event. For participants without switching, last day of study or follow up period was regarded as censored. Percentage of participants who switched to TRIPLE therapy was calculated as: number of participants who switched to TRIPLE therapy divided by number of evaluable population and then multiplied by 100. |
| Change From Baseline in CAT Total Score | Baseline and up to 24 weeks | Participants were assessed for COPD symptoms by means of CAT at each Visit. This assessment was performed prior to the spirometry testing. A CAT total score of less than 10 represents best health status and greater than 15 represents worst health status. Baseline was the value at Visit 2 (randomization). Change from Baseline was calculated as specific timepoint value minus Visit 2 value. Scores were assessed at Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). Scores range from 0 to 40, high value in score indicate worse outcome. |
| Forced Expiratory Volume in One Second (FEV1) | Up to 24 weeks | FEV1 is defined as the volume of air forcefully expelled from the lungs in one second. At Screening (Visit 1) spirometric assessments were conducted before (Visit 1A) and 30 to 60 minutes after a bronchodilator challenge (400 µg of salbutamol) (Visit 1B). FEV1 during each visit are presented. FEV1 was assessed at Visit 1A (Screening), Visit 1B (Screening), Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). |
| Change From Baseline in FEV1 | Baseline (Visit 2) and up to 24 weeks | FEV1 is defined as the volume of air forcefully expelled from the lungs in one second. Baseline was a value at Visit 2 (randomization). Change from Baseline was calculated as specific timepoint value minus Visit 2 value. FEV1 was assessed at Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). |
| Percentage of Participants Who Used Relief Medication (Salbutamol) | 24 weeks | Each evening participants recorded the number of occasions in the last 24 hours when they used their salbutamol for symptomatic relief of COPD symptoms. The percentage of participants who used relief medication in the study are presented. |
| Percentage of Participants Who Stepped Down From TRIPLE Therapy to Initial Randomized Treatment | 24 weeks | The percentage of participants who stepped down from TRIPLE therapy to initial randomized treatment was calculated as number of participants who step-down from TRIPLE therapy divided by number of participants who switch to TRIPLE therapy and then multiplied by 100. |
| Percentage of Participants Who Required Additional Treatment to TRIPLE Therapy | 24 weeks | The percentage of participants who required additional treatment to TRIPLE therapy is defined as number of participants who took additional medicine or therapy in TRIPLE therapy divided by number of participants who switch to TRIPLE therapy multiplied by 100. |
| Percentage of Participants Who Dropped Out | 24 weeks | The percentage of participants who were withdrawn from the study. |
| Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Up to 24 weeks | Participants evaluated treatment efficacy by using the following grades: significantly improved (SII), moderately improved (MOI), mildly improved (MII), no change (NC), mildly worse (MIW), moderately worse (MOW), and significantly worse (SIW). Treatment efficacy was assessed at Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). |
| Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | 24 weeks | Physician evaluated treatment efficacy by using the following grades: significantly improved (SII), moderately improved (MOI), mildly improved (MII), no change (NC), mildly worse (MIW), moderately worse (MOW), and significantly worse (SIW). Treatment efficacy was assessed at Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). |
| Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | 24 weeks | Participants were assessed for COPD symptoms by means of CAT at each Visit. This assessment was performed prior to the spirometry testing. A CAT total score of less than 10 represents best health status and greater than 15 represents worst health status. Scores were assessed at Visit 1 (Screening), Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). Scores range from 0 to 40, high value in score indicate worse outcome. |
Countries
Japan
Participant flow
Pre-assignment details
A total of 570 participants were screened, 428 participants entered into the run-in period, 406 participants were randomized into the study (incorrectly 407 on protocol summary due to miss operation at study site that cannot be corrected), and 405 participant received study medication and comprised the modified Intent to Treat (mITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| TIO 18 µg QD Participants received 18 µg TIO QD via HandiHaler inhaler and placebo BID via DPI, during the 24-week study treatment period. Participants also received 400 µg salbutamol as relief medication and as a bronchodilator for pulmonary function testing as required throughout the study. | 201 |
| SAL/FLU 50/250 µg BID Participants received 50/250 µg SAL/FLU BID via DPI and placebo QD via HandiHaler inhaler, during the 24-week study treatment period. Participants also received 400 µg salbutamol as relief medication and as a bronchodilator for pulmonary function testing as required throughout the study. | 204 |
| Total | 405 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 13 |
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Study Closed/Terminated | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 4 |
Baseline characteristics
| Characteristic | SAL/FLU 50/250 µg BID | Total | TIO 18 µg QD |
|---|---|---|---|
| Age, Continuous | 68.6 Years STANDARD_DEVIATION 6.93 | 68.3 Years STANDARD_DEVIATION 7.02 | 68.0 Years STANDARD_DEVIATION 7.12 |
| Race/Ethnicity, Customized African American/African Heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 203 Participants | 404 Participants | 201 Participants |
| Sex: Female, Male Female | 12 Participants | 20 Participants | 8 Participants |
| Sex: Female, Male Male | 192 Participants | 385 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 126 | 29 / 75 | 48 / 136 | 25 / 68 |
| serious Total, serious adverse events | 8 / 126 | 8 / 75 | 8 / 136 | 6 / 68 |
Outcome results
Primary
Percentage of Participants Who Were Able to Remain on the Randomized Treatment
The randomized treatment could be switched to TRIPLE therapy in the case that chronic obstructive pulmonary disease (COPD) is not controlled by the randomized treatment. Participants on TRIPLE therapy received SAL/FLU 50/250 µg BID plus TIO 18 µg QD together. The percentage of participants who were able to remain on the randomized treatment was calculated by the following formula: 100 minus percentage of participants who switched over to TRIPLE therapy.
Time frame: 24 weeks
Population: Modified Intent-to-Treat (mITT) population: randomized participants who received at least a single dose of the investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Percentage of Participants Who Were Able to Remain on the Randomized Treatment | 62.69 Percentage of participants |
| SAL/FLU 50/250 µg BID | Percentage of Participants Who Were Able to Remain on the Randomized Treatment | 66.67 Percentage of participants |
Secondary
Change From Baseline in CAT Total Score
Participants were assessed for COPD symptoms by means of CAT at each Visit. This assessment was performed prior to the spirometry testing. A CAT total score of less than 10 represents best health status and greater than 15 represents worst health status. Baseline was the value at Visit 2 (randomization). Change from Baseline was calculated as specific timepoint value minus Visit 2 value. Scores were assessed at Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). Scores range from 0 to 40, high value in score indicate worse outcome.
Time frame: Baseline and up to 24 weeks
Population: mITT population. Only those participants available at the specified time points (represented by n=X, X, X, X in the category titles) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | Change From Baseline in CAT Total Score | Visit 3, n=132, 68, 121, 75 | -1.6 Scores on a scale | Standard Deviation 4.74 |
| TIO 18 µg QD | Change From Baseline in CAT Total Score | Visit 4, n=127, 68, 116, 74 | -1.7 Scores on a scale | Standard Deviation 5.34 |
| TIO 18 µg QD | Change From Baseline in CAT Total Score | Visit 5, n=123, 68, 116, 73 | -1.6 Scores on a scale | Standard Deviation 6.04 |
| TIO 18 µg QD | Change From Baseline in CAT Total Score | Visit 6, n=120, 66, 115, 74 | -2.3 Scores on a scale | Standard Deviation 5.41 |
| TIO 18 µg QD | Change From Baseline in CAT Total Score | Visit 7, n=120, 66, 113, 71 | -2.0 Scores on a scale | Standard Deviation 5.5 |
| TIO 18 µg QD | Change From Baseline in CAT Total Score | Visit 8, n=117, 66, 113, 70 | -2.4 Scores on a scale | Standard Deviation 5.74 |
| SAL/FLU 50/250 µg BID | Change From Baseline in CAT Total Score | Visit 8, n=117, 66, 113, 70 | -1.0 Scores on a scale | Standard Deviation 6.05 |
| SAL/FLU 50/250 µg BID | Change From Baseline in CAT Total Score | Visit 6, n=120, 66, 115, 74 | 0.0 Scores on a scale | Standard Deviation 6.28 |
| SAL/FLU 50/250 µg BID | Change From Baseline in CAT Total Score | Visit 3, n=132, 68, 121, 75 | 0.1 Scores on a scale | Standard Deviation 4.52 |
| SAL/FLU 50/250 µg BID | Change From Baseline in CAT Total Score | Visit 5, n=123, 68, 116, 73 | -0.8 Scores on a scale | Standard Deviation 5.68 |
| SAL/FLU 50/250 µg BID | Change From Baseline in CAT Total Score | Visit 4, n=127, 68, 116, 74 | -0.2 Scores on a scale | Standard Deviation 5.68 |
| SAL/FLU 50/250 µg BID | Change From Baseline in CAT Total Score | Visit 7, n=120, 66, 113, 71 | -0.8 Scores on a scale | Standard Deviation 6.2 |
| TIO 18 µg QD-Single | Change From Baseline in CAT Total Score | Visit 4, n=127, 68, 116, 74 | -0.3 Scores on a scale | Standard Deviation 4.21 |
| TIO 18 µg QD-Single | Change From Baseline in CAT Total Score | Visit 5, n=123, 68, 116, 73 | -0.7 Scores on a scale | Standard Deviation 5.14 |
| TIO 18 µg QD-Single | Change From Baseline in CAT Total Score | Visit 6, n=120, 66, 115, 74 | -0.7 Scores on a scale | Standard Deviation 4.55 |
| TIO 18 µg QD-Single | Change From Baseline in CAT Total Score | Visit 8, n=117, 66, 113, 70 | -1.4 Scores on a scale | Standard Deviation 4.93 |
| TIO 18 µg QD-Single | Change From Baseline in CAT Total Score | Visit 7, n=120, 66, 113, 71 | -0.8 Scores on a scale | Standard Deviation 4.91 |
| TIO 18 µg QD-Single | Change From Baseline in CAT Total Score | Visit 3, n=132, 68, 121, 75 | 0.1 Scores on a scale | Standard Deviation 3.97 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in CAT Total Score | Visit 7, n=120, 66, 113, 71 | -0.6 Scores on a scale | Standard Deviation 5.49 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in CAT Total Score | Visit 8, n=117, 66, 113, 70 | -0.5 Scores on a scale | Standard Deviation 6.29 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in CAT Total Score | Visit 4, n=127, 68, 116, 74 | 1.6 Scores on a scale | Standard Deviation 5.53 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in CAT Total Score | Visit 6, n=120, 66, 115, 74 | 0.0 Scores on a scale | Standard Deviation 6.09 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in CAT Total Score | Visit 3, n=132, 68, 121, 75 | 2.1 Scores on a scale | Standard Deviation 5.1 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in CAT Total Score | Visit 5, n=123, 68, 116, 73 | 0.8 Scores on a scale | Standard Deviation 5.78 |
Secondary
Change From Baseline in FEV1
FEV1 is defined as the volume of air forcefully expelled from the lungs in one second. Baseline was a value at Visit 2 (randomization). Change from Baseline was calculated as specific timepoint value minus Visit 2 value. FEV1 was assessed at Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24).
Time frame: Baseline (Visit 2) and up to 24 weeks
Population: mITT population. Only those participants available at the specified time points (represented by n=X, X, X, X in the category titles) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | Change From Baseline in FEV1 | Visit 3; n=131, 68, 119, 75 | 0.024 Liters | Standard Deviation 0.1917 |
| TIO 18 µg QD | Change From Baseline in FEV1 | Visit 4; n=127, 68, 116, 74 | 0.008 Liters | Standard Deviation 0.2092 |
| TIO 18 µg QD | Change From Baseline in FEV1 | Visit 5; n=122, 68, 116, 72 | -0.010 Liters | Standard Deviation 0.2066 |
| TIO 18 µg QD | Change From Baseline in FEV1 | Visit 6; n=120, 66, 114, 74 | -0.007 Liters | Standard Deviation 0.2069 |
| TIO 18 µg QD | Change From Baseline in FEV1 | Visit 7; n=119, 66, 113, 71 | -0.012 Liters | Standard Deviation 0.2252 |
| TIO 18 µg QD | Change From Baseline in FEV1 | Visit 8; n=117, 66, 113, 70 | -0.019 Liters | Standard Deviation 0.2293 |
| SAL/FLU 50/250 µg BID | Change From Baseline in FEV1 | Visit 8; n=117, 66, 113, 70 | 0.049 Liters | Standard Deviation 0.1892 |
| SAL/FLU 50/250 µg BID | Change From Baseline in FEV1 | Visit 6; n=120, 66, 114, 74 | 0.027 Liters | Standard Deviation 0.2025 |
| SAL/FLU 50/250 µg BID | Change From Baseline in FEV1 | Visit 3; n=131, 68, 119, 75 | -0.043 Liters | Standard Deviation 0.1825 |
| SAL/FLU 50/250 µg BID | Change From Baseline in FEV1 | Visit 5; n=122, 68, 116, 72 | -0.001 Liters | Standard Deviation 0.191 |
| SAL/FLU 50/250 µg BID | Change From Baseline in FEV1 | Visit 4; n=127, 68, 116, 74 | -0.030 Liters | Standard Deviation 0.1821 |
| SAL/FLU 50/250 µg BID | Change From Baseline in FEV1 | Visit 7; n=119, 66, 113, 71 | 0.018 Liters | Standard Deviation 0.1874 |
| TIO 18 µg QD-Single | Change From Baseline in FEV1 | Visit 4; n=127, 68, 116, 74 | -0.011 Liters | Standard Deviation 0.1977 |
| TIO 18 µg QD-Single | Change From Baseline in FEV1 | Visit 5; n=122, 68, 116, 72 | -0.006 Liters | Standard Deviation 0.2002 |
| TIO 18 µg QD-Single | Change From Baseline in FEV1 | Visit 6; n=120, 66, 114, 74 | 0.002 Liters | Standard Deviation 0.1893 |
| TIO 18 µg QD-Single | Change From Baseline in FEV1 | Visit 8; n=117, 66, 113, 70 | -0.017 Liters | Standard Deviation 0.2355 |
| TIO 18 µg QD-Single | Change From Baseline in FEV1 | Visit 7; n=119, 66, 113, 71 | -0.010 Liters | Standard Deviation 0.222 |
| TIO 18 µg QD-Single | Change From Baseline in FEV1 | Visit 3; n=131, 68, 119, 75 | 0.007 Liters | Standard Deviation 0.1772 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in FEV1 | Visit 7; n=119, 66, 113, 71 | 0.050 Liters | Standard Deviation 0.2091 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in FEV1 | Visit 8; n=117, 66, 113, 70 | 0.027 Liters | Standard Deviation 0.1999 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in FEV1 | Visit 4; n=127, 68, 116, 74 | -0.032 Liters | Standard Deviation 0.2325 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in FEV1 | Visit 6; n=120, 66, 114, 74 | 0.037 Liters | Standard Deviation 0.2098 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in FEV1 | Visit 3; n=131, 68, 119, 75 | -0.077 Liters | Standard Deviation 0.1843 |
| TIO 18 µg QD-TRIPLE | Change From Baseline in FEV1 | Visit 5; n=122, 68, 116, 72 | 0.005 Liters | Standard Deviation 0.2171 |
Secondary
Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score
Participants were assessed for COPD symptoms by means of CAT at each Visit. This assessment was performed prior to the spirometry testing. A CAT total score of less than 10 represents best health status and greater than 15 represents worst health status. Scores were assessed at Visit 1 (Screening), Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24). Scores range from 0 to 40, high value in score indicate worse outcome.
Time frame: 24 weeks
Population: mITT population. Only those participants available at the specified time points (represented by n=X, X, X, X in the category titles) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 1, n=136, 68, 126, 75 | 11.3 Scores on a scale | Standard Deviation 5.83 |
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 2, n=136, 68, 126, 75 | 9.9 Scores on a scale | Standard Deviation 6.35 |
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 3, n=132, 68, 121, 75 | 8.4 Scores on a scale | Standard Deviation 6.09 |
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 4, n=127, 68, 116, 74 | 8.3 Scores on a scale | Standard Deviation 5.99 |
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 5, n=123, 68, 116, 73 | 8.3 Scores on a scale | Standard Deviation 7.12 |
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 6, n=120, 66, 115, 74 | 7.4 Scores on a scale | Standard Deviation 6.11 |
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 7, n=120, 66, 113, 71 | 7.7 Scores on a scale | Standard Deviation 6.51 |
| TIO 18 µg QD | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 8, n=117, 66, 113, 70 | 7.2 Scores on a scale | Standard Deviation 6.42 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 6, n=120, 66, 115, 74 | 13.3 Scores on a scale | Standard Deviation 8.26 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 5, n=123, 68, 116, 73 | 12.6 Scores on a scale | Standard Deviation 7.56 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 2, n=136, 68, 126, 75 | 13.4 Scores on a scale | Standard Deviation 7.52 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 8, n=117, 66, 113, 70 | 12.3 Scores on a scale | Standard Deviation 7.56 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 7, n=120, 66, 113, 71 | 12.4 Scores on a scale | Standard Deviation 7.69 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 4, n=127, 68, 116, 74 | 13.2 Scores on a scale | Standard Deviation 7.59 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 3, n=132, 68, 121, 75 | 13.5 Scores on a scale | Standard Deviation 8.12 |
| SAL/FLU 50/250 µg BID | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 1, n=136, 68, 126, 75 | 13.3 Scores on a scale | Standard Deviation 6.35 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 7, n=120, 66, 113, 71 | 8.3 Scores on a scale | Standard Deviation 6.48 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 3, n=132, 68, 121, 75 | 9.2 Scores on a scale | Standard Deviation 5.91 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 4, n=127, 68, 116, 74 | 8.8 Scores on a scale | Standard Deviation 5.89 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 5, n=123, 68, 116, 73 | 8.4 Scores on a scale | Standard Deviation 5.89 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 6, n=120, 66, 115, 74 | 8.5 Scores on a scale | Standard Deviation 5.75 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 8, n=117, 66, 113, 70 | 7.8 Scores on a scale | Standard Deviation 5.79 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 1, n=136, 68, 126, 75 | 11.2 Scores on a scale | Standard Deviation 5.77 |
| TIO 18 µg QD-Single | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 2, n=136, 68, 126, 75 | 9.6 Scores on a scale | Standard Deviation 6.27 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 3, n=132, 68, 121, 75 | 14.3 Scores on a scale | Standard Deviation 7.28 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 4, n=127, 68, 116, 74 | 13.6 Scores on a scale | Standard Deviation 6.65 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 2, n=136, 68, 126, 75 | 12.1 Scores on a scale | Standard Deviation 6.08 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 1, n=136, 68, 126, 75 | 13.4 Scores on a scale | Standard Deviation 6.49 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 5, n=123, 68, 116, 73 | 12.8 Scores on a scale | Standard Deviation 7.02 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 8, n=117, 66, 113, 70 | 11.6 Scores on a scale | Standard Deviation 7.7 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 7, n=120, 66, 113, 71 | 11.4 Scores on a scale | Standard Deviation 7.09 |
| TIO 18 µg QD-TRIPLE | Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score | Visit 6, n=120, 66, 115, 74 | 12.0 Scores on a scale | Standard Deviation 7.52 |
Secondary
Comparison of Number of Exacerbations Between Two Detection Methods: EXACT and Physician Diagnosis
The comparison of number of exacerbation between two detection methods EXACT and physician diagnosis: number of exacerbations detected by EXACT and number of exacerbations judged by physician.
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | Comparison of Number of Exacerbations Between Two Detection Methods: EXACT and Physician Diagnosis | Physician's diagnosis | 0.2 Number of exacerbations | Standard Deviation 0.44 |
| TIO 18 µg QD | Comparison of Number of Exacerbations Between Two Detection Methods: EXACT and Physician Diagnosis | EXACT | 0.9 Number of exacerbations | Standard Deviation 1 |
| SAL/FLU 50/250 µg BID | Comparison of Number of Exacerbations Between Two Detection Methods: EXACT and Physician Diagnosis | EXACT | 0.7 Number of exacerbations | Standard Deviation 1.06 |
| SAL/FLU 50/250 µg BID | Comparison of Number of Exacerbations Between Two Detection Methods: EXACT and Physician Diagnosis | Physician's diagnosis | 0.1 Number of exacerbations | Standard Deviation 0.36 |
Secondary
Continuation Percentage of Participants Managed by Randomized Treatment Plus TRIPLE Therapy
The randomized treatment could be switched to TRIPLE therapy in the case that chronic obstructive pulmonary disease (COPD) was not controlled by the randomized treatment. Participants on TRIPLE therapy received SAL/FLU 50/250 µg BID plus TIO 18 µg QD together. Continuation TRIPLE proportion is defined as \[(number of subjects who switched to TRIPLE) - (number of subjects who stepped down)/ number of evaluable population\]\*100. Randomised treatment continuation proportion is calculated by a formula: (100 - switch proportion).
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIO 18 µg QD | Continuation Percentage of Participants Managed by Randomized Treatment Plus TRIPLE Therapy | Randomised treatment | 62.69 Percentage of participants |
| TIO 18 µg QD | Continuation Percentage of Participants Managed by Randomized Treatment Plus TRIPLE Therapy | TRIPLE therapy | 36.82 Percentage of participants |
| SAL/FLU 50/250 µg BID | Continuation Percentage of Participants Managed by Randomized Treatment Plus TRIPLE Therapy | Randomised treatment | 66.67 Percentage of participants |
| SAL/FLU 50/250 µg BID | Continuation Percentage of Participants Managed by Randomized Treatment Plus TRIPLE Therapy | TRIPLE therapy | 32.35 Percentage of participants |
Secondary
E-RS Subscale Score
The E-RS total score is an 11-item patient questionnaire, which provides information specific to respiratory symptoms-severity of respiratory symptoms overall and severity of breathlessness, cough and sputum, and chest symptoms. The E-RS subscale scores for respiratory symptoms (RS)-breathlessness (RS-BRL), RS-cough and sputum (RS-CSP), and RS-chest symptoms (RS-CSY) are presented. Scores were assessed at Baseline, Week 1-4, Week 5-8, Week 9-12, Week 13-16, Week 17-20 and at Week 21-24. Daily EXACT total score is obtained as total score of 14 items from diary. Daily E-RS total score as 11 items and Daily E-RS subscale scores are subset of E-RS total score. Mean EXACT total score is mean value of daily EXACT total score within subject by every 4 weeks(Week1-4, Week5-8, Week9-12, Week13-16, Week17-20, Week21-24). Same calculation of mean values are applied to E-RS total and E-RS subscale scores. RS total scores range from 0 to 40, high value in score indicate worse outcome.
Time frame: 24 weeks
Population: mITT population. Only those participants available at the specified time points (represented by n=X, X, X, X in the category titles) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | E-RS Subscale Score | RS-CSP; Week 17-20; n=119, 66, 114, 72 | 2.06 Scores on a scale | Standard Deviation 1.612 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSP; Week 13-16; n=121, 66, 116, 74 | 1.98 Scores on a scale | Standard Deviation 1.563 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSP; Baseline; n=135, 68, 124, 73 | 2.29 Scores on a scale | Standard Deviation 1.536 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSY; Week 17-20; n=119, 66, 114, 72 | 1.48 Scores on a scale | Standard Deviation 1.802 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSP; Week 9-12; n=122, 68, 116, 74 | 2.06 Scores on a scale | Standard Deviation 1.85 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSP; Week 5-8; n=126, 68, 116, 73 | 2.03 Scores on a scale | Standard Deviation 1.448 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSP; Week 1-4; n=131, 68, 121, 75 | 2.12 Scores on a scale | Standard Deviation 1.453 |
| TIO 18 µg QD | E-RS Subscale Score | RS-BRL; Week 9-12; n=122, 68, 116, 74 | 3.08 Scores on a scale | Standard Deviation 3.402 |
| TIO 18 µg QD | E-RS Subscale Score | RS-BRL; Baseline; n=135, 68, 125, 73 | 3.36 Scores on a scale | Standard Deviation 3.113 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSY; Week 13-16; n=121, 66, 116, 74 | 1.46 Scores on a scale | Standard Deviation 1.752 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSY; Week 9-12; n=122, 68, 116, 74 | 1.54 Scores on a scale | Standard Deviation 2.032 |
| TIO 18 µg QD | E-RS Subscale Score | RS-BRL; Week 13-16; n=121, 66, 116, 74 | 2.80 Scores on a scale | Standard Deviation 3.151 |
| TIO 18 µg QD | E-RS Subscale Score | RS-BRL; Week 5-8; n=126, 68, 115, 73 | 3.08 Scores on a scale | Standard Deviation 3.281 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSY; Week 5-8; n=126, 68, 116, 73 | 1.65 Scores on a scale | Standard Deviation 1.76 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSY; Week 1-4; n=131, 68, 121, 75 | 1.58 Scores on a scale | Standard Deviation 1.652 |
| TIO 18 µg QD | E-RS Subscale Score | RS-BRL; Week 17-20; n=118, 66, 114, 72 | 2.82 Scores on a scale | Standard Deviation 3.349 |
| TIO 18 µg QD | E-RS Subscale Score | RS-BRL; Week 1-4; n=131, 68, 121, 75 | 3.06 Scores on a scale | Standard Deviation 3.245 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSY; Baseline; n=135, 67, 125, 73 | 1.77 Scores on a scale | Standard Deviation 1.768 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSP; Week 21-24; n=93, 51, 94, 51 | 1.82 Scores on a scale | Standard Deviation 1.711 |
| TIO 18 µg QD | E-RS Subscale Score | RS-BRL; Week 21-24; n=93, 51, 94, 51 | 2.79 Scores on a scale | Standard Deviation 3.316 |
| TIO 18 µg QD | E-RS Subscale Score | RS-CSY; Week 21-24; n=93, 51, 94, 51 | 1.38 Scores on a scale | Standard Deviation 1.944 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-BRL; Week 1-4; n=131, 68, 121, 75 | 6.28 Scores on a scale | Standard Deviation 3.498 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-BRL; Week 5-8; n=126, 68, 115, 73 | 5.96 Scores on a scale | Standard Deviation 3.517 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-BRL; Week 9-12; n=122, 68, 116, 74 | 5.87 Scores on a scale | Standard Deviation 3.612 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-BRL; Week 13-16; n=121, 66, 116, 74 | 5.81 Scores on a scale | Standard Deviation 3.683 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-BRL; Week 17-20; n=118, 66, 114, 72 | 5.56 Scores on a scale | Standard Deviation 3.678 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-BRL; Week 21-24; n=93, 51, 94, 51 | 4.94 Scores on a scale | Standard Deviation 3.661 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSP; Baseline; n=135, 68, 124, 73 | 2.73 Scores on a scale | Standard Deviation 1.778 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSP; Week 1-4; n=131, 68, 121, 75 | 2.90 Scores on a scale | Standard Deviation 1.687 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSP; Week 5-8; n=126, 68, 116, 73 | 2.83 Scores on a scale | Standard Deviation 1.814 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSP; Week 9-12; n=122, 68, 116, 74 | 2.81 Scores on a scale | Standard Deviation 1.766 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSP; Week 13-16; n=121, 66, 116, 74 | 2.74 Scores on a scale | Standard Deviation 1.769 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSP; Week 17-20; n=119, 66, 114, 72 | 2.43 Scores on a scale | Standard Deviation 1.608 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSP; Week 21-24; n=93, 51, 94, 51 | 2.27 Scores on a scale | Standard Deviation 1.604 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSY; Baseline; n=135, 67, 125, 73 | 2.93 Scores on a scale | Standard Deviation 1.903 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSY; Week 1-4; n=131, 68, 121, 75 | 3.21 Scores on a scale | Standard Deviation 2.071 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSY; Week 5-8; n=126, 68, 116, 73 | 3.05 Scores on a scale | Standard Deviation 1.977 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSY; Week 9-12; n=122, 68, 116, 74 | 3.12 Scores on a scale | Standard Deviation 2.069 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSY; Week 13-16; n=121, 66, 116, 74 | 3.11 Scores on a scale | Standard Deviation 2.102 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSY; Week 17-20; n=119, 66, 114, 72 | 2.81 Scores on a scale | Standard Deviation 1.873 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-CSY; Week 21-24; n=93, 51, 94, 51 | 2.61 Scores on a scale | Standard Deviation 1.988 |
| SAL/FLU 50/250 µg BID | E-RS Subscale Score | RS-BRL; Baseline; n=135, 68, 125, 73 | 5.81 Scores on a scale | Standard Deviation 3.542 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSY; Baseline; n=135, 67, 125, 73 | 1.84 Scores on a scale | Standard Deviation 1.729 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-BRL; Week 5-8; n=126, 68, 115, 73 | 3.18 Scores on a scale | Standard Deviation 3.11 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSY; Week 9-12; n=122, 68, 116, 74 | 1.60 Scores on a scale | Standard Deviation 1.584 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSP; Week 21-24; n=93, 51, 94, 51 | 1.99 Scores on a scale | Standard Deviation 1.68 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-BRL; Week 9-12; n=122, 68, 116, 74 | 2.98 Scores on a scale | Standard Deviation 2.97 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-BRL; Week 1-4; n=131, 68, 121, 75 | 3.36 Scores on a scale | Standard Deviation 3.288 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSY; Week 13-16; n=121, 66, 116, 74 | 1.70 Scores on a scale | Standard Deviation 1.623 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSY; Week 21-24; n=93, 51, 94, 51 | 1.64 Scores on a scale | Standard Deviation 1.741 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSP; Week 1-4; n=131, 68, 121, 75 | 2.13 Scores on a scale | Standard Deviation 1.517 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSY; Week 1-4; n=131, 68, 121, 75 | 1.69 Scores on a scale | Standard Deviation 1.681 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-BRL; Week 21-24; n=93, 51, 94, 51 | 2.95 Scores on a scale | Standard Deviation 3.16 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-BRL; Week 13-16; n=121, 66, 116, 74 | 3.04 Scores on a scale | Standard Deviation 3.084 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSP; Week 5-8; n=126, 68, 116, 73 | 2.13 Scores on a scale | Standard Deviation 1.633 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-BRL; Week 17-20; n=118, 66, 114, 72 | 3.04 Scores on a scale | Standard Deviation 3.254 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSP; Baseline; n=135, 68, 124, 73 | 2.23 Scores on a scale | Standard Deviation 1.643 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-BRL; Baseline; n=135, 68, 125, 73 | 3.41 Scores on a scale | Standard Deviation 3.122 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSP; Week 9-12; n=122, 68, 116, 74 | 2.11 Scores on a scale | Standard Deviation 1.635 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSY; Week 5-8; n=126, 68, 116, 73 | 1.70 Scores on a scale | Standard Deviation 1.695 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSP; Week 17-20; n=119, 66, 114, 72 | 2.09 Scores on a scale | Standard Deviation 1.702 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSY; Week 17-20; n=119, 66, 114, 72 | 1.72 Scores on a scale | Standard Deviation 1.908 |
| TIO 18 µg QD-Single | E-RS Subscale Score | RS-CSP; Week 13-16; n=121, 66, 116, 74 | 2.09 Scores on a scale | Standard Deviation 1.579 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-BRL; Week 9-12; n=122, 68, 116, 74 | 5.52 Scores on a scale | Standard Deviation 3.793 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSY; Week 17-20; n=119, 66, 114, 72 | 2.55 Scores on a scale | Standard Deviation 2.171 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSP; Week 17-20; n=119, 66, 114, 72 | 2.40 Scores on a scale | Standard Deviation 1.768 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-BRL; Week 17-20; n=118, 66, 114, 72 | 4.94 Scores on a scale | Standard Deviation 3.908 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSP; Week 21-24; n=93, 51, 94, 51 | 2.34 Scores on a scale | Standard Deviation 1.783 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-BRL; Baseline; n=135, 68, 125, 73 | 5.62 Scores on a scale | Standard Deviation 3.393 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSY; Baseline; n=135, 67, 125, 73 | 2.92 Scores on a scale | Standard Deviation 1.794 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-BRL; Week 13-16; n=121, 66, 116, 74 | 5.11 Scores on a scale | Standard Deviation 4.029 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSY; Week 1-4; n=131, 68, 121, 75 | 3.59 Scores on a scale | Standard Deviation 2.306 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSY; Week 21-24; n=93, 51, 94, 51 | 2.53 Scores on a scale | Standard Deviation 2.167 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSY; Week 5-8; n=126, 68, 116, 73 | 2.99 Scores on a scale | Standard Deviation 2.149 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSP; Week 13-16; n=121, 66, 116, 74 | 2.49 Scores on a scale | Standard Deviation 1.797 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-BRL; Week 1-4; n=131, 68, 121, 75 | 6.59 Scores on a scale | Standard Deviation 4.191 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSY; Week 9-12; n=122, 68, 116, 74 | 3.01 Scores on a scale | Standard Deviation 2.204 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSY; Week 13-16; n=121, 66, 116, 74 | 2.66 Scores on a scale | Standard Deviation 2.184 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSP; Week 1-4; n=131, 68, 121, 75 | 3.05 Scores on a scale | Standard Deviation 1.925 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSP; Baseline; n=135, 68, 124, 73 | 2.81 Scores on a scale | Standard Deviation 1.601 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-BRL; Week 5-8; n=126, 68, 115, 73 | 5.38 Scores on a scale | Standard Deviation 3.857 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSP; Week 5-8; n=126, 68, 116, 73 | 2.74 Scores on a scale | Standard Deviation 1.763 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-CSP; Week 9-12; n=122, 68, 116, 74 | 2.77 Scores on a scale | Standard Deviation 1.803 |
| TIO 18 µg QD-TRIPLE | E-RS Subscale Score | RS-BRL; Week 21-24; n=93, 51, 94, 51 | 4.71 Scores on a scale | Standard Deviation 4.159 |
Secondary
EXACT Respiratory Symptoms (E-RS) Total Score
The E-RS total score is an 11-item patient questionnaire, which provides information specific to respiratory symptoms-severity of respiratory symptoms overall and severity of breathlessness, cough and sputum, and chest symptoms. Scores were assessed at Baseline, Week 1-4, Week 5-8, Week 9-12, Week 13-16, Week 17-20 and at Week 21-24. Daily EXACT total score is obtained as total score of 14 items from diary. Daily E-RS total score as 11 items and Daily E-RS subscale scores are subset of E-RS total score. Mean EXACT total score is mean value of daily EXACT total score within subject by every 4 weeks(Week1-4, Week5-8, Week9-12, Week13-16, Week17-20, Week21-24). Same calculation of mean values are applied to E-RS total and E-RS subscale scores. Scores range from 0-100, high value in score indicate worse outcome.
Time frame: Baseline and up to 24 weeks
Population: mITT population. Only those participants available at the specified time points (represented by n=X, X, X, X in the category titles) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | EXACT Respiratory Symptoms (E-RS) Total Score | Week 9-12; n=122, 68, 116, 74 | 6.69 Scores on a scale | Standard Deviation 6.489 |
| TIO 18 µg QD | EXACT Respiratory Symptoms (E-RS) Total Score | Week 17-20; n=118, 66, 114, 72 | 6.33 Scores on a scale | Standard Deviation 5.786 |
| TIO 18 µg QD | EXACT Respiratory Symptoms (E-RS) Total Score | Week 13-16; n=121, 66, 116, 74 | 6.23 Scores on a scale | Standard Deviation 5.667 |
| TIO 18 µg QD | EXACT Respiratory Symptoms (E-RS) Total Score | Week 1-4; n=131, 68, 121, 75 | 6.76 Scores on a scale | Standard Deviation 5.405 |
| TIO 18 µg QD | EXACT Respiratory Symptoms (E-RS) Total Score | Baseline; n=135, 67, 124, 73 | 7.42 Scores on a scale | Standard Deviation 5.541 |
| TIO 18 µg QD | EXACT Respiratory Symptoms (E-RS) Total Score | Week 21-24; n=93, 51, 94, 51 | 5.99 Scores on a scale | Standard Deviation 6.044 |
| TIO 18 µg QD | EXACT Respiratory Symptoms (E-RS) Total Score | Week 5-8; n=126, 68, 115, 73 | 6.75 Scores on a scale | Standard Deviation 5.618 |
| SAL/FLU 50/250 µg BID | EXACT Respiratory Symptoms (E-RS) Total Score | Baseline; n=135, 67, 124, 73 | 11.43 Scores on a scale | Standard Deviation 6.378 |
| SAL/FLU 50/250 µg BID | EXACT Respiratory Symptoms (E-RS) Total Score | Week 21-24; n=93, 51, 94, 51 | 9.82 Scores on a scale | Standard Deviation 6.507 |
| SAL/FLU 50/250 µg BID | EXACT Respiratory Symptoms (E-RS) Total Score | Week 17-20; n=118, 66, 114, 72 | 10.80 Scores on a scale | Standard Deviation 6.158 |
| SAL/FLU 50/250 µg BID | EXACT Respiratory Symptoms (E-RS) Total Score | Week 9-12; n=122, 68, 116, 74 | 11.79 Scores on a scale | Standard Deviation 6.696 |
| SAL/FLU 50/250 µg BID | EXACT Respiratory Symptoms (E-RS) Total Score | Week 13-16; n=121, 66, 116, 74 | 11.66 Scores on a scale | Standard Deviation 6.739 |
| SAL/FLU 50/250 µg BID | EXACT Respiratory Symptoms (E-RS) Total Score | Week 5-8; n=126, 68, 115, 73 | 11.86 Scores on a scale | Standard Deviation 6.573 |
| SAL/FLU 50/250 µg BID | EXACT Respiratory Symptoms (E-RS) Total Score | Week 1-4; n=131, 68, 121, 75 | 12.39 Scores on a scale | Standard Deviation 6.533 |
| TIO 18 µg QD-Single | EXACT Respiratory Symptoms (E-RS) Total Score | Week 21-24; n=93, 51, 94, 51 | 6.58 Scores on a scale | Standard Deviation 5.702 |
| TIO 18 µg QD-Single | EXACT Respiratory Symptoms (E-RS) Total Score | Baseline; n=135, 67, 124, 73 | 7.51 Scores on a scale | Standard Deviation 5.583 |
| TIO 18 µg QD-Single | EXACT Respiratory Symptoms (E-RS) Total Score | Week 1-4; n=131, 68, 121, 75 | 7.18 Scores on a scale | Standard Deviation 5.745 |
| TIO 18 µg QD-Single | EXACT Respiratory Symptoms (E-RS) Total Score | Week 5-8; n=126, 68, 115, 73 | 6.99 Scores on a scale | Standard Deviation 5.72 |
| TIO 18 µg QD-Single | EXACT Respiratory Symptoms (E-RS) Total Score | Week 9-12; n=122, 68, 116, 74 | 6.70 Scores on a scale | Standard Deviation 5.244 |
| TIO 18 µg QD-Single | EXACT Respiratory Symptoms (E-RS) Total Score | Week 13-16; n=121, 66, 116, 74 | 6.82 Scores on a scale | Standard Deviation 5.392 |
| TIO 18 µg QD-Single | EXACT Respiratory Symptoms (E-RS) Total Score | Week 17-20; n=118, 66, 114, 72 | 6.85 Scores on a scale | Standard Deviation 6.035 |
| TIO 18 µg QD-TRIPLE | EXACT Respiratory Symptoms (E-RS) Total Score | Week 9-12; n=122, 68, 116, 74 | 11.30 Scores on a scale | Standard Deviation 6.762 |
| TIO 18 µg QD-TRIPLE | EXACT Respiratory Symptoms (E-RS) Total Score | Week 5-8; n=126, 68, 115, 73 | 11.11 Scores on a scale | Standard Deviation 6.798 |
| TIO 18 µg QD-TRIPLE | EXACT Respiratory Symptoms (E-RS) Total Score | Week 21-24; n=93, 51, 94, 51 | 9.59 Scores on a scale | Standard Deviation 7.42 |
| TIO 18 µg QD-TRIPLE | EXACT Respiratory Symptoms (E-RS) Total Score | Week 17-20; n=118, 66, 114, 72 | 9.89 Scores on a scale | Standard Deviation 7.073 |
| TIO 18 µg QD-TRIPLE | EXACT Respiratory Symptoms (E-RS) Total Score | Week 1-4; n=131, 68, 121, 75 | 13.23 Scores on a scale | Standard Deviation 7.37 |
| TIO 18 µg QD-TRIPLE | EXACT Respiratory Symptoms (E-RS) Total Score | Baseline; n=135, 67, 124, 73 | 11.36 Scores on a scale | Standard Deviation 5.65 |
| TIO 18 µg QD-TRIPLE | EXACT Respiratory Symptoms (E-RS) Total Score | Week 13-16; n=121, 66, 116, 74 | 10.26 Scores on a scale | Standard Deviation 7.122 |
Secondary
EXACT Total Score.
EXACT is a 14-item patient questionnaire used as a measure of respiratory symptoms (reported as units on a 0 \[best health status\] to 100 \[worst possible status\] scale). Scores were assessed at Baseline, Week 1-4, Week 5-8, Week 9-12, Week 13-16, Week 17-20 and Week 21-24. Daily EXACT total score is obtained as total score of 14 items from diary. Daily E-RS total score as 11 items and Daily E-RS subscale scores are subset of E-RS total score. Mean EXACT total score is mean value of daily EXACT total score within subject by every 4 weeks(Week1-4, Week5-8, Week9-12, Week13-16, Week17-20, Week21-24). Same calculation of mean values are applied to E-RS total and E-RS subscale scores.
Time frame: Baseline and up to 24 weeks
Population: mITT population. Only those participants available at the specified time points (represented by n=X, X, X, X in the category titles) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | EXACT Total Score. | Baseline; n=125, 66, 111, 71 | 28.99 Scores on a scale | Standard Deviation 10.151 |
| TIO 18 µg QD | EXACT Total Score. | Week 17-20; n=107, 65, 97, 66 | 26.98 Scores on a scale | Standard Deviation 10.971 |
| TIO 18 µg QD | EXACT Total Score. | Week 13-16; n=105, 65, 100, 71 | 27.33 Scores on a scale | Standard Deviation 10.715 |
| TIO 18 µg QD | EXACT Total Score. | Week 1-4; n=120, 67, 109, 73 | 27.83 Scores on a scale | Standard Deviation 10.225 |
| TIO 18 µg QD | EXACT Total Score. | Week 21-24; n=79, 51, 77, 46 | 26.50 Scores on a scale | Standard Deviation 11.697 |
| TIO 18 µg QD | EXACT Total Score. | Week 5-8; n=117, 63, 102, 69 | 27.35 Scores on a scale | Standard Deviation 10.921 |
| TIO 18 µg QD | EXACT Total Score. | Week 9-12; n=109, 67, 101, 72 | 27.63 Scores on a scale | Standard Deviation 11.847 |
| SAL/FLU 50/250 µg BID | EXACT Total Score. | Week 17-20; n=107, 65, 97, 66 | 34.92 Scores on a scale | Standard Deviation 10.661 |
| SAL/FLU 50/250 µg BID | EXACT Total Score. | Week 9-12; n=109, 67, 101, 72 | 36.16 Scores on a scale | Standard Deviation 11.492 |
| SAL/FLU 50/250 µg BID | EXACT Total Score. | Week 5-8; n=117, 63, 102, 69 | 37.58 Scores on a scale | Standard Deviation 9.831 |
| SAL/FLU 50/250 µg BID | EXACT Total Score. | Week 13-16; n=105, 65, 100, 71 | 35.92 Scores on a scale | Standard Deviation 11.55 |
| SAL/FLU 50/250 µg BID | EXACT Total Score. | Week 21-24; n=79, 51, 77, 46 | 32.72 Scores on a scale | Standard Deviation 11.992 |
| SAL/FLU 50/250 µg BID | EXACT Total Score. | Week 1-4; n=120, 67, 109, 73 | 36.92 Scores on a scale | Standard Deviation 10.385 |
| SAL/FLU 50/250 µg BID | EXACT Total Score. | Baseline; n=125, 66, 111, 71 | 36.00 Scores on a scale | Standard Deviation 10.499 |
| TIO 18 µg QD-Single | EXACT Total Score. | Week 9-12; n=109, 67, 101, 72 | 28.40 Scores on a scale | Standard Deviation 9.619 |
| TIO 18 µg QD-Single | EXACT Total Score. | Baseline; n=125, 66, 111, 71 | 29.77 Scores on a scale | Standard Deviation 10.163 |
| TIO 18 µg QD-Single | EXACT Total Score. | Week 1-4; n=120, 67, 109, 73 | 28.88 Scores on a scale | Standard Deviation 10.182 |
| TIO 18 µg QD-Single | EXACT Total Score. | Week 5-8; n=117, 63, 102, 69 | 28.80 Scores on a scale | Standard Deviation 10.274 |
| TIO 18 µg QD-Single | EXACT Total Score. | Week 13-16; n=105, 65, 100, 71 | 28.93 Scores on a scale | Standard Deviation 9.721 |
| TIO 18 µg QD-Single | EXACT Total Score. | Week 17-20; n=107, 65, 97, 66 | 28.66 Scores on a scale | Standard Deviation 10.97 |
| TIO 18 µg QD-Single | EXACT Total Score. | Week 21-24; n=79, 51, 77, 46 | 28.80 Scores on a scale | Standard Deviation 10.497 |
| TIO 18 µg QD-TRIPLE | EXACT Total Score. | Week 5-8; n=117, 63, 102, 69 | 35.87 Scores on a scale | Standard Deviation 11.117 |
| TIO 18 µg QD-TRIPLE | EXACT Total Score. | Week 21-24; n=79, 51, 77, 46 | 33.67 Scores on a scale | Standard Deviation 12.722 |
| TIO 18 µg QD-TRIPLE | EXACT Total Score. | Week 17-20; n=107, 65, 97, 66 | 34.03 Scores on a scale | Standard Deviation 12.066 |
| TIO 18 µg QD-TRIPLE | EXACT Total Score. | Week 1-4; n=120, 67, 109, 73 | 38.26 Scores on a scale | Standard Deviation 12.23 |
| TIO 18 µg QD-TRIPLE | EXACT Total Score. | Baseline; n=125, 66, 111, 71 | 35.78 Scores on a scale | Standard Deviation 9.222 |
| TIO 18 µg QD-TRIPLE | EXACT Total Score. | Week 13-16; n=105, 65, 100, 71 | 33.79 Scores on a scale | Standard Deviation 12.334 |
| TIO 18 µg QD-TRIPLE | EXACT Total Score. | Week 9-12; n=109, 67, 101, 72 | 35.57 Scores on a scale | Standard Deviation 11.578 |
Secondary
Forced Expiratory Volume in One Second (FEV1)
FEV1 is defined as the volume of air forcefully expelled from the lungs in one second. At Screening (Visit 1) spirometric assessments were conducted before (Visit 1A) and 30 to 60 minutes after a bronchodilator challenge (400 µg of salbutamol) (Visit 1B). FEV1 during each visit are presented. FEV1 was assessed at Visit 1A (Screening), Visit 1B (Screening), Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24).
Time frame: Up to 24 weeks
Population: mITT population. Only those participants available at the specified time points (represented by n=X, X, X, X in the category titles) were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 8; n=117, 66, 113, 70 | 1.694 Liters | Standard Deviation 0.4808 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 5; n=122, 68, 116, 72 | 1.718 Liters | Standard Deviation 0.4859 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 1B; n=136, 68, 126, 75 | 1.764 Liters | Standard Deviation 0.4363 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 4; n=127, 68, 116, 74 | 1.713 Liters | Standard Deviation 0.4943 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 2; n=136, 68, 126, 75 | 1.695 Liters | Standard Deviation 0.465 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 6; n=120, 66, 114, 74 | 1.716 Liters | Standard Deviation 0.4817 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 1A; n=136, 68, 126, 75 | 1.687 Liters | Standard Deviation 0.444 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 3; n=131, 68, 119, 75 | 1.731 Liters | Standard Deviation 0.4904 |
| TIO 18 µg QD | Forced Expiratory Volume in One Second (FEV1) | Visit 7; n=119, 66, 113, 71 | 1.710 Liters | Standard Deviation 0.485 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 1B; n=136, 68, 126, 75 | 1.471 Liters | Standard Deviation 0.4394 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 7; n=119, 66, 113, 71 | 1.404 Liters | Standard Deviation 0.4913 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 1A; n=136, 68, 126, 75 | 1.401 Liters | Standard Deviation 0.4482 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 4; n=127, 68, 116, 74 | 1.355 Liters | Standard Deviation 0.4555 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 2; n=136, 68, 126, 75 | 1.385 Liters | Standard Deviation 0.4336 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 5; n=122, 68, 116, 72 | 1.384 Liters | Standard Deviation 0.4497 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 3; n=131, 68, 119, 75 | 1.342 Liters | Standard Deviation 0.4563 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 6; n=120, 66, 114, 74 | 1.413 Liters | Standard Deviation 0.5104 |
| SAL/FLU 50/250 µg BID | Forced Expiratory Volume in One Second (FEV1) | Visit 8; n=117, 66, 113, 70 | 1.435 Liters | Standard Deviation 0.4871 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 2; n=136, 68, 126, 75 | 1.681 Liters | Standard Deviation 0.4929 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 3; n=131, 68, 119, 75 | 1.710 Liters | Standard Deviation 0.5458 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 4; n=127, 68, 116, 74 | 1.703 Liters | Standard Deviation 0.5215 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 5; n=122, 68, 116, 72 | 1.708 Liters | Standard Deviation 0.5408 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 6; n=120, 66, 114, 74 | 1.712 Liters | Standard Deviation 0.5353 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 1A; n=136, 68, 126, 75 | 1.675 Liters | Standard Deviation 0.4564 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 1B; n=136, 68, 126, 75 | 1.754 Liters | Standard Deviation 0.4691 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 7; n=119, 66, 113, 71 | 1.694 Liters | Standard Deviation 0.5402 |
| TIO 18 µg QD-Single | Forced Expiratory Volume in One Second (FEV1) | Visit 8; n=117, 66, 113, 70 | 1.688 Liters | Standard Deviation 0.5426 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 1B; n=136, 68, 126, 75 | 1.429 Liters | Standard Deviation 0.4346 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 5; n=122, 68, 116, 72 | 1.376 Liters | Standard Deviation 0.4536 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 4; n=127, 68, 116, 74 | 1.336 Liters | Standard Deviation 0.4638 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 8; n=117, 66, 113, 70 | 1.390 Liters | Standard Deviation 0.4695 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 7; n=119, 66, 113, 71 | 1.423 Liters | Standard Deviation 0.4916 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 3; n=131, 68, 119, 75 | 1.285 Liters | Standard Deviation 0.457 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 1A; n=136, 68, 126, 75 | 1.349 Liters | Standard Deviation 0.4032 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 6; n=120, 66, 114, 74 | 1.405 Liters | Standard Deviation 0.4938 |
| TIO 18 µg QD-TRIPLE | Forced Expiratory Volume in One Second (FEV1) | Visit 2; n=136, 68, 126, 75 | 1.362 Liters | Standard Deviation 0.4267 |
Secondary
Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants
Participants evaluated treatment efficacy by using the following grades: significantly improved (SII), moderately improved (MOI), mildly improved (MII), no change (NC), mildly worse (MIW), moderately worse (MOW), and significantly worse (SIW). Treatment efficacy was assessed at Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24).
Time frame: Up to 24 weeks
Population: mITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MIW | 4 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MII | 27 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SII | 2 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOI | 13 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOI | 13 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MII | 35 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; NC | 66 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; NC | 58 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; SII | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SII | 5 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SIW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SIW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; SII | 3 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MII | 35 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MII | 39 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOI | 15 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MII | 31 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOI | 9 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; NC | 67 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MIW | 10 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; NC | 74 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; SII | 5 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SII | 2 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOI | 9 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOI | 13 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MIW | 5 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MII | 31 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MIW | 7 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MIW | 4 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; NC | 66 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MIW | 10 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; NC | 75 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SIW | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MIW | 5 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOI | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; NC | 39 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MIW | 5 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOI | 4 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOI | 4 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOW | 5 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MII | 17 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MIW | 8 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MII | 16 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SII | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; SII | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MII | 17 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; NC | 33 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SIW | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOW | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOW | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MIW | 11 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; NC | 32 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SIW | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOW | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOW | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SIW | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; NC | 34 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MII | 19 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MIW | 19 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; NC | 37 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; NC | 37 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOI | 7 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOI | 6 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MII | 10 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOI | 4 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MIW | 7 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MII | 12 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SIW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SII | 1 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOI | 3 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MII | 20 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; NC | 85 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MIW | 9 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOW | 3 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SIW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOI | 5 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MII | 25 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; NC | 79 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MIW | 5 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOI | 3 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MII | 31 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; NC | 78 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MIW | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOI | 4 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MII | 30 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; NC | 72 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MIW | 7 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SIW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOI | 5 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MII | 28 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; NC | 71 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MIW | 7 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOI | 8 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MII | 30 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; NC | 69 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MIW | 3 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOW | 1 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOW | 3 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SII | 1 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MII | 20 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MIW | 9 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; NC | 31 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; NC | 34 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; NC | 26 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MII | 20 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; MOI | 6 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; NC | 32 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MIW | 9 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SII | 4 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOW | 5 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MII | 7 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOW | 1 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MIW | 13 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; NC | 28 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOW | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; SII | 4 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MII | 21 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; MOI | 6 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MIW | 4 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MOI | 9 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 4; SII | 1 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; SIW | 1 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOI | 3 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOW | 2 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MIW | 7 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 8; MII | 19 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SIW | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; NC | 34 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MII | 14 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MOW | 9 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; SII | 4 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; MOI | 13 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 6; SII | 4 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 3; MIW | 22 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 7; MOI | 11 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants | Visit 5; SIW | 0 Participants |
Secondary
Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician
Physician evaluated treatment efficacy by using the following grades: significantly improved (SII), moderately improved (MOI), mildly improved (MII), no change (NC), mildly worse (MIW), moderately worse (MOW), and significantly worse (SIW). Treatment efficacy was assessed at Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 8), Visit 6 (Week 12), Visit 7 (Week 16), and Visit 8 (Week 24).
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SIW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MII | 40 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; NC | 74 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; NC | 79 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOI | 14 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MIW | 6 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MIW | 3 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; SII | 2 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SII | 2 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MII | 25 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SIW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; NC | 67 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SIW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MII | 28 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MII | 31 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SII | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; NC | 70 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOI | 7 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOI | 12 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SIW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MIW | 1 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOI | 11 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MII | 29 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SII | 3 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MIW | 3 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MIW | 7 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; NC | 73 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; SII | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MII | 36 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; NC | 74 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MIW | 7 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOI | 13 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOW | 0 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOI | 10 Participants |
| TIO 18 µg QD | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SII | 6 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOW | 6 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SIW | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; NC | 39 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOW | 8 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOI | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; NC | 33 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MII | 18 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; NC | 33 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MIW | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MIW | 11 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SIW | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOW | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MII | 13 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOI | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SIW | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOW | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOI | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOW | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MIW | 12 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SII | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MII | 12 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; SII | 1 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SIW | 0 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; NC | 38 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; NC | 31 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SII | 2 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOI | 3 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOI | 6 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOI | 4 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MII | 18 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MII | 14 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; NC | 35 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MIW | 16 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MIW | 10 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MII | 19 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MIW | 5 Participants |
| SAL/FLU 50/250 µg BID | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOW | 1 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MIW | 5 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MII | 23 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; NC | 77 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MIW | 5 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOI | 5 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOW | 1 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; SII | 3 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOI | 7 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOI | 8 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MII | 27 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; NC | 71 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MIW | 4 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOW | 1 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MII | 23 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; NC | 79 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MII | 21 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MIW | 4 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SIW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; NC | 83 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOI | 4 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SII | 1 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MII | 22 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; NC | 83 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOI | 5 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MIW | 7 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SIW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SII | 2 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOI | 3 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOW | 3 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MII | 28 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; NC | 72 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MIW | 10 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SIW | 1 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SIW | 0 Participants |
| TIO 18 µg QD-Single | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; SII | 2 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; NC | 32 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SII | 1 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOI | 4 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MII | 3 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; NC | 32 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MIW | 23 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; MOW | 12 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 3; SIW | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SII | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOI | 9 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MII | 18 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; NC | 27 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MIW | 12 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; MOW | 8 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 4; SIW | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SII | 4 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOI | 8 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MII | 19 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; NC | 29 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MIW | 10 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; MOW | 3 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 5; SIW | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SII | 2 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOI | 11 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MII | 17 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOW | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MIW | 9 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; MOW | 3 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; NC | 35 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 6; SIW | 0 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; SII | 3 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOI | 12 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MII | 12 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MIW | 8 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 7; MOW | 1 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; SII | 3 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MOI | 9 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MII | 13 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; NC | 40 Participants |
| TIO 18 µg QD-TRIPLE | Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician | Visit 8; MIW | 5 Participants |
Secondary
Percentage of Participants Managed by TRIPLE Therapy
Percentage of participants managed by TRIPLE therapy was calculated as \[(number of participants who switched to TRIPLE therapy) - (number of participants who stepped down)/ number of evaluable population\]\*100
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Percentage of Participants Managed by TRIPLE Therapy | 36.82 Percentage of participants |
| SAL/FLU 50/250 µg BID | Percentage of Participants Managed by TRIPLE Therapy | 32.35 Percentage of participants |
Secondary
Percentage of Participants Who Dropped Out
The percentage of participants who were withdrawn from the study.
Time frame: 24 weeks
Population: All Subjects population: all participants who were enrolled into the study and whose data obtained at screening (visit1) was not missing and demography data was available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Percentage of Participants Who Dropped Out | 9 Percentage of participants |
| SAL/FLU 50/250 µg BID | Percentage of Participants Who Dropped Out | 10 Percentage of participants |
Secondary
Percentage of Participants Who Required Additional Treatment to TRIPLE Therapy
The percentage of participants who required additional treatment to TRIPLE therapy is defined as number of participants who took additional medicine or therapy in TRIPLE therapy divided by number of participants who switch to TRIPLE therapy multiplied by 100.
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Percentage of Participants Who Required Additional Treatment to TRIPLE Therapy | 77.33 Percentage of participants |
| SAL/FLU 50/250 µg BID | Percentage of Participants Who Required Additional Treatment to TRIPLE Therapy | 72.06 Percentage of participants |
Secondary
Percentage of Participants Who Stepped Down From TRIPLE Therapy to Initial Randomized Treatment
The percentage of participants who stepped down from TRIPLE therapy to initial randomized treatment was calculated as number of participants who step-down from TRIPLE therapy divided by number of participants who switch to TRIPLE therapy and then multiplied by 100.
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Percentage of Participants Who Stepped Down From TRIPLE Therapy to Initial Randomized Treatment | 1.33 Percentage of participants |
| SAL/FLU 50/250 µg BID | Percentage of Participants Who Stepped Down From TRIPLE Therapy to Initial Randomized Treatment | 2.94 Percentage of participants |
Secondary
Percentage of Participants Who Switched to TRIPLE Therapy
Switched to TRIPLE therapy is defined as: 1. Date of switch: when SAL/FLU or TIO was administered additionally to randomised treatment. 2. Date of randomisation was a start point and timing of switching (first switch if there are more than once) to TRIPLE was event. For participants without switching, last day of study or follow up period was regarded as censored. Percentage of participants who switched to TRIPLE therapy was calculated as: number of participants who switched to TRIPLE therapy divided by number of evaluable population and then multiplied by 100.
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Percentage of Participants Who Switched to TRIPLE Therapy | 37.31 Percentage of participants |
| SAL/FLU 50/250 µg BID | Percentage of Participants Who Switched to TRIPLE Therapy | 33.33 Percentage of participants |
Secondary
Percentage of Participants Who Used Relief Medication (Salbutamol)
Each evening participants recorded the number of occasions in the last 24 hours when they used their salbutamol for symptomatic relief of COPD symptoms. The percentage of participants who used relief medication in the study are presented.
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Percentage of Participants Who Used Relief Medication (Salbutamol) | 40.4 Percentage of participants |
| SAL/FLU 50/250 µg BID | Percentage of Participants Who Used Relief Medication (Salbutamol) | 61.8 Percentage of participants |
| TIO 18 µg QD-Single | Percentage of Participants Who Used Relief Medication (Salbutamol) | 43.7 Percentage of participants |
| TIO 18 µg QD-TRIPLE | Percentage of Participants Who Used Relief Medication (Salbutamol) | 70.7 Percentage of participants |
Secondary
Time to First Exacerbation by EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)
The EXAcerbations of Chronic pulmonary disease Tool (EXACT) is a 14-item patient-reported outcome (PRO) daily diary used to quantify and measure exacerbations of chronic obstructive pulmonary disease (COPD). Reported as units on a 0 \[best health status\] to 100 \[worst possible status\] scale). The day of detection of first exacerbation in any participant in each arm by EXACT.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Time to First Exacerbation by EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) | 0 Days |
| SAL/FLU 50/250 µg BID | Time to First Exacerbation by EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) | 0 Days |
| TIO 18 µg QD-Single | Time to First Exacerbation by EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) | 0 Days |
| TIO 18 µg QD-TRIPLE | Time to First Exacerbation by EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) | 1 Days |
Secondary
Time to First Exacerbation by Physician's Diagnosis
The day of detection of first exacerbation in any participant in each arm as diagnosed by physician. Exacerbation is defined primarily by physician's judgment. Date of randomisation will be start point and timing of exacerbation (first exacerbation if there are more than one) will be event. For subjects without exacerbation, last day of study or follow up period is regarded as censor.
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Time to First Exacerbation by Physician's Diagnosis | 3 Days |
| SAL/FLU 50/250 µg BID | Time to First Exacerbation by Physician's Diagnosis | 5 Days |
| TIO 18 µg QD-Single | Time to First Exacerbation by Physician's Diagnosis | 10 Days |
| TIO 18 µg QD-TRIPLE | Time to First Exacerbation by Physician's Diagnosis | 2 Days |
Secondary
Time to First Switching to TRIPLE Therapy
The day of first switch to TRIPLE therapy (SAL/FLU 50/250 µg BID+TIO 18 µg QD) for the first switching participant in each arm.
Time frame: 24 weeks
Population: mITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TIO 18 µg QD | Time to First Switching to TRIPLE Therapy | 5 Days |
| SAL/FLU 50/250 µg BID | Time to First Switching to TRIPLE Therapy | 5 Days |