Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Triple Therapy, Formoterol, Respiratory, COPD, Budesonide, Vilanterol, Fluticasone Furoate, Umeclidinium, Lung Function
Brief summary
This is a phase IIIa, randomised, double-blind, double-dummy, parallel group multicenter study evaluating once daily FF/UMEC/VI (100 microgram \[mcg\]/62.5 mcg/25 mcg) inhalation powder versus twice daily budesonide/formoterol (400 mcg/12 mcg). The primary purpose of this study is to demonstrate improvements in lung function and health status for subjects treated with FF/UMEC/VI compared with budesonide/formoterol for 24 weeks. Once-daily 'closed' triple therapy of a Inhaled Corticosteroid/ Long-acting Muscarinic Receptor Antagonists/ Long Acting Beta-Agonist (ICS/LAMA/LABA) combination FF/UMEC/VI (100 mcg/62.5 mcg/25 mcg) in a single device is being developed with the aim of providing a new treatment option for the management of advanced (GOLD Group D) COPD which will reduce the exacerbation frequency, allow for a reduced burden of polypharmacy, convenience, and increase the potential for improvement in lung function, Health Related Quality of Life (HRQoL) and symptom control over established dual/monotherapies. Subjects meeting all inclusion/exclusion criteria and who have successfully completed all protocol procedures at the Screening Visit will enter the two-week run-in period. Following the run-in period, eligible subjects will be randomised (1:1) to one of the following double-blind treatment groups: FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg via the ELLIPTA™ dry powder inhaler (DPI) once daily in the morning and placebo via reservoir inhaler twice daily OR Budesonide/formoterol 400 mcg/12 mcg via reservoir inhaler twice daily and placebo via the ELLIPTA DPI once daily in the morning. The target enrollment is 1800 randomised subjects at approximately 200 study centers globally. The total duration of subject participation will be approximately 27 weeks, consisting of a 2-week run-in period, 24-week treatment period and a 1-week follow-up period. Subjects will run-in on their existing COPD medications for 2 weeks and in addition will be provided with short acting albuterol/salbutamol to be used on an as-needed basis (rescue medication) throughout the study. Subjects will discontinue all existing COPD medications during the randomised treatment period but may continue their study supplied rescue albuterol/salbutamol. A sub-set of approximately 400 subjects will remain on blinded study treatment for up to a total of 52 weeks to provide additional long term safety data. ELLIPTA and NUBULES are a trade marks of the GlaxoSmithKline Group of Companies. Other company or product names mentioned herein may be the property of their respective owners
Interventions
DRUGTriple FF/UMEC/VI
The combination will be provided as inhalation via an ELLIPTA DPI having 30 doses (2 strips with 30 blisters per strip). It will have 100 mcg of FF (blended with lactose) per blister, 62.5 mcg of UMEC (blended with lactose and magnesium stearate) per blister and 25 mcg of VI (blended with lactose) per blister.
The placebo (Lactose) will be provided as inhalation via an ELLIPTA DPI having 30 doses (2 strips with 30 blisters per strip).
DRUGBudesonide/Formoterol
The combination (400 mcg Budesonide/12 mcg Formoterol) will be provided as inhalation via TURBOHALER with 60 doses.
DRUGPlacebo to match Budesonide/Formoterol combination
The placebo (Lactose) will be provided as inhalation via TURBOHALER with 60 doses.
DRUGAlbuterol/salbutamol
Albuterol/salbutamol will be available as an inhalation via metered-dose inhaler (MDI) with a spacer and will be issued for reversibility testing at Visit 1 Albuterol/salbutamol MDI or NEBULES™ for as needed (prn) use throughout the study will be provided starting at Visit 1.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed Consent: A signed and dated written informed consent prior to study participation. * Type of subject: Outpatient. * Age: Subjects 40 years of age or older at Screening (Visit 1). * Gender: Male or female subjects. A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, \>45 years, in the absence of hormone replacement therapy. OR Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to safety follow-up contact): Abstinence, Oral Contraceptive, either combined or progestogen alone, Injectable progestogen, Implants of levonorgestrel, Estrogenic vaginal ring, Percutaneous contraceptive patches, Intrauterine device (IUD) or intrauterine system (IUS), Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, documented refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records.; Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository) * COPD Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society. * Smoking History: Current or former cigarette smokers with a history of cigarette smoking of \>10 pack-years at Screening (Visit 1) \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Note: Pipe and/or cigar use cannot be used to calculate pack-year history. * Severity of COPD symptoms: A score of \>=10 on the COPD Assessment Test (CAT) at Screening (Visit 1). * Severity of Disease: Subjects must demonstrate at Screening: \<a post-bronchodilator FEV1 \<50% predicted normal OR a post-bronchodilator FEV1 \<80% predicted normal and a documented history of \>=2 moderate exacerbations or one severe (hospitalized) exacerbation in the previous 12 months. Subjects must also have a measured post albuterol/salbutamol FEV1/FVC ratio of \<0.70 at screening. Note: Percent predicted will be calculated using the European Respiratory Society Global Lung Function Initiative reference equations. Note: A documented history of a COPD exacerbation (e.g., medical record verification) is a medical record of worsening COPD symptoms that required systemic/oral corticosteroids and/or antibiotics (for a moderate exacerbation) or hospitalization (for a severe exacerbation). Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnoea, sputum volume, or sputum purulence (colour). Subject verbal reports are not acceptable. * Existing COPD maintenance treatment: Subject must be receiving daily maintenance treatment for their COPD for at least 3 months prior to Screening. Note: Subjects receiving only as required (PRN) COPD medications are not eligible. * Liver function tests: alanine aminotransferase (ALT) \<2x upper limit of normal (ULN); alkaline phosphatase \<=1.5xULN; bilirubin \<=1.5xULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
Exclusion criteria
* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study. * Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD). Alpha1-antitrypsin deficiency: Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD. * Other respiratory disorders: Subjects with active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. * Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening. * Risk Factors for Pneumonia: immune suppression (e.g. Human immunodeficiency virus \[HIV\], Lupus) or other risk factors for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson's Disease, Myasthenia Gravis). Subjects at potentially high risk (e.g. very low Body mass index \[BMI\], severely malnourished, or very low FEV1) will only be included at the discretion of the investigator. * Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable). In addition, any subject that experiences pneumonia and/or moderate or severe COPD exacerbation during the run-in period will be excluded. * Respiratory tract infection that has not resolved at least 7 days prior to Screening. * Abnormal Chest X-ray (CXR): Chest X-ray (posteroanterior and lateral) reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD, or another condition that would hinder the ability to detect an infiltrate on CXR (e.g. significant cardiomegaly, pleural effusion or scarring). All subjects will have a CXR at Screening Visit 1) (or historical radiograph or Computed Tomography \[CT\] scan obtained within 3 months prior to screening) that will be over-read by a central vendor. Note: Subjects who have experienced pneumonia and/or moderate or severe COPD exacerbation within 3 months of screening must provide a post pneumonia/exacerbation CXR to be over-read by the central vendor or have a CXR conducted at Screening. For sites in Germany: If a chest x-ray (or CT scan) within 3 months prior to Screening (Visit 1) is not available, approval to conduct a diagnostic CXR will need to be obtained from the Federal Office for Radiation Protection (BfS). * Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. For subjects taking part in the physical activity monitor subset: Orthopaedic, neurological or other complaints that significantly impair normal biomechanical movement patterns and limit the ability to walk/cycle, as judged by the Investigator. * Unstable liver disease as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Note: Chronic stable hepatitis B and C are acceptable if the subject otherwise meets entry criteria. * Unstable or life threatening cardiac disease: subjects with any of the following at Screening (Visit 1) would be excluded: Myocardial infarction or unstable angina in the last 6 months; Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure * Abnormal and clinically significant 12-Lead Electrocardiogram (ECG) finding: Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The Principal Investigator (PI) will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. An abnormal and clinically significant finding that would preclude a subject from entering the trial is defined as a 12-lead tracing that is interpreted as, but not limited to, any of the following: Atrial fibrillation (AF) with rapid ventricular rate \>120 Beats Per Minute (BPM); sustained or non-sustained ventricular tachycardia (VT); Second degree heart block Mobitz type II and third degree heart block (unless pacemaker or defibrillator had been inserted); QT interval corrected for heart rate by Fridericia's formula (QTcF) \>=500 milliseconds (msec) in subjects with QRS \<120 msec and QTcF \>=530 msec in subjects with QRS \>=120 msec. * Contraindications: A history of allergy or hypersensitivity to any corticosteroid, anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the Investigator, contraindicates study participation. * Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5 year waiting period if the subject has been considered cured by treatment. * Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy \>3litres/minute (L/min) (Oxygen use \<=3L/min flow is not exclusionary.) * Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol for the 4-hour period required prior to spirometry testing at each study visit. * Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening or subjects who plan to enter the acute phase of a Pulmonary Rehabilitation Program during the study. Subjects who are in the maintenance phase of a Pulmonary Rehabilitation Program are not excluded. * Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years. * Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits. * Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study. * Affiliation with investigator site: study investigators, sub-investigators, study coordinators, employees of a participating investigator or study site, or immediate family members of the aforementioned that is involved with this study. * Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete study related materials. * Medication prior to screening: No use of the following medications within the following time intervals prior to Screening or during the study. Long term antibiotic therapy: Subjects receiving antibiotics for long term therapy are not eligible for the study (Antibiotics are allowed for the short term treatment of an exacerbation or for short term treatment of other acute infections); Systemic, Oral, parenteral corticosteroids: 30 days (Except during the study oral/systemic corticosteroids may be used to treat COPD exacerbations/pneumonia). Intra-articular injections are allowed. Any other investigational drug: 30 days or 5 half lives whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24 | Baseline to Week 24 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. ITT Population comprised of all randomized subjects excluding those who were randomized in error. Only participants with analyzable data at the given time point were analyzed. |
| Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 52 | Baseline to Week 52 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 52 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. Extension Population: all participants in the ITT Population who were enrolled into the subset of participants with extension to 52 weeks. |
| Change From Baseline in St George's Respiratory Questionnaire-Chronic Obstructive Pulmonary Disease (COPD; SGRQ) Total Score for COPD Participants at Week 24 | Baseline to Week 24 | The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 24 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions |
| Change From Baseline in St George's Respiratory Questionnaire-COPD; SGRQ Total Score for COPD Participants at Week 52 | Baseline to Week 52 | The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 52 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 24 | Up to Week 24 | The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant \[par.\] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence \[color\]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, \>=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1). |
| Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 52 | Up to Week 52 | The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant \[par.\] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence \[color\]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, \>=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1). |
| Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Baseline to Week 24 | The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). |
| Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Baseline to Week 52 | The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). |
| Number of Participants With Any On-treatment Adverse Event (AE) and Serious Adverse Event (SAE) in the Treatment Period | Up to Week 24 | An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint. |
| Number of Participants With Any On-treatment AE/SAEs in the Extension Part of the Study | Up to Week 52 | An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint. |
| Number of Participants With an On-treatment Penumonia Event in the Treatment Period | Up to Week 24 | All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray and at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature \> 37.5 °C), Elevated white blood cells (WBC) (\>10,000/millimeter \[mm\^3\] or \>15 percent immature forms) or Hypoxemia (hemoglobin/oxygen \[HbO2\] saturation \<88 percent or at least 2 percent lower than Baseline value). |
| Number of Participants With an On-treatment Penumonia Event in the Extension Part of the Study | Up to Week 52 | All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray AND at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature \> 37.5 °C), Elevated WBC (\>10,000/mm3 or \>15 percent immature forms) orr Hypoxemia (HbO2 saturation \<88 percent or at least 2 percent lower than Baseline value). |
| Number of Participants With Any On-treatment Cardiovascular (CV) Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Treatment Period | Up to Week 24 | Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query \[SMQ; myocardial infarction SMQ and other ischemic diseases\]) and narrow MACE criteria (myocardial infarction \[acute myocardial infarction\]. |
| Number of Participants With Any On-treatment CV Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Extension Part of the Study | Up to Week 52 | Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query \[SMQ; myocardial infarction SMQ and other ischemic diseases\]) and narrow MACE criteria (myocardial infarction \[acute myocardial infarction\] |
| Change From Baseline in Heart Rate at Week 24 | Baseline and Week 24 | A single 12-lead electrocardiogram (ECG) and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. |
| Change From Baseline in Heart Rate at Week 52 | Baseline and Week 52 | A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. |
| Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) and PR Interval at Week 24 | Baseline and Week 24 | A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. |
| Change From Baseline in QTcF and PR Interval at Week 52 | Baseline and Week 52 | Single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). |
| Change From Baseline in QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Week 24 | Baseline and Week 24 | A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. |
| Change From Baseline in QTcB at Week 52 | Baseline and Week 52 | A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24, and Week 52 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 52. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading. |
| Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 24 | Baseline and Week 24 | Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were collected taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat). |
| Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 52 | Baseline and Week 52 | Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 52 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat). |
| Number of Participants With Any Abnormal Holter Electrocardiogram (ECG) Finding at Week 24 | Up to Week 24 | The 24-hour holter measurements were obtained at Screening and 24 hours prior to Week 24 (Visits 1 and 6). The number of participants with clinically significant change (abnormal) were reported. Holter Monitoring Population: all participants in the ITT Population who had at least one holter monitoring evaluation. |
| Change From Baseline in Pulse Rate at Week 24 | Baseline and Week 24 | Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat). |
| Change From Baseline in Pulse Rate at Week 52 | Baseline and Week 52 | Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 52 were summarized and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat). |
| Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Baseline and Week 24 | Hematology laboratory assessments included basophils, eosinophils, lymphocytes, monocytes, neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a repeat test). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Baseline and Week 52 | Hematology laboratory assessments included Basophils, eosinophils, lymphocytes, monocytes,neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Erythrocytes at Week 24 | Baseline and Week 24 | Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Erythrocytes at Week 52 | Baseline and Week 52 | Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Hemoglobin at Week 24 | Baseline and Week 24 | Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Hemoglobin at Week 52 | Baseline and Week 52 | Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Hematocrit at Week 24 | Baseline and Week 24 | Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Hematocrit at Week 52 | Baseline and Week 52 | Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as Most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Albumin and Protein at Week 24 | Baseline and Week 24 | Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12 and Week 24. Change from Baseline (BL) was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). The maximum post BL values have been presented. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Albumin and Protein at Week 52 | Baseline and Week 52 | Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Baseline and Week 24 | Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12 and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Baseline and Week 52 | Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12, Week 24 and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Baseline and Week 24 | Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, phophate, potassium, sodium, and urea at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Baseline and Week 52 | Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, magnesium, phophate, potassium, sodium, and urea at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Baseline and Week 24 | Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented. |
| Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Baseline and Week 52 | Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, Week 24, and Week 52 of the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). |
| Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Up to Week 24 | Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, Candida infection, oral fungal infection, and oropharyngeal candidiasis were reported. |
| Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 24 | Week 24 | The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Week 4 and Week 24. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions. |
| Number of Participants With at Least One On-treatment Bone Fracture Incident in the Treatment Period | Up to Week 24 | To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest. |
| Number of Participants With at Least One On-treatment Bone Fracture Incident in the Extension Part of the Study | Up to Week 52 | To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest. |
| Number of Participants Reporting an AESI of Oropharyngeal Origin in the Extension Part of the Study | Up to Week 52 | Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, candida infection, oral fungal infection, and oropharyngeal candidiasis were reported. |
| Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 52 | Week 52 | The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Weeks 4, 24 and 52. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions |
| Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 24 | Up to Week 24 | Participants were asked to complete the daily activity question as part of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline. |
| Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 52 | Up to Week 52 | Participants were asked to complete the daily activity question as aprt of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline. |
Countries
Bulgaria, China, Czechia, Estonia, Germany, Greece, Hungary, Italy, Mexico, Poland, Romania, Russia, Slovakia, South Korea, Ukraine
Participant flow
Recruitment details
This was a phase IIIa, randomized, double-blind, double-dummy, parallel group multicenter study to evaluate once daily fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI; 100 micrograms \[µg\]/62.5 µg/25 µg) inhalation versus twice daily budesonide/formoterol (400 µg/12 µg) in participants with chronic obstructive pulmonary disease.
Pre-assignment details
A total of 2121 participants were screened in this study and 1811 were randomized following 2-week run-in. Of those, 1 participant was randomized in error and did not receive randomized treatment. This was followed by a 24-week treatment and 1-week follow-up periods. A sub-set of 430 participants continued in a blinded study treatment for 52 weeks.
Participants by arm
| Arm | Count |
|---|---|
| FF/UMEC/VI 100/62.5/25 µg Participants received FF/UMEC/VI 100/62.5/25 µg via the ELLIPTA dry powder inhaler (DPI) once daily in the morning and placebo via the Turbuhaler twice daily (BID) for 24 weeks in the treatment period and 52 weeks for participants in the extension part of the study. | 911 |
| BUD/FOR 400/12 µg Participants received BUD/FOR 400/12 µg via the Turbuhaler BID and placebo via the ELLIPTA once daily in the morning for 24 weeks in the treatment period and 52 weeks for participants in the extension part of the study. | 899 |
| Total | 1,810 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 19 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 4 | 4 |
| Overall Study | Withdrawal by Subject | 25 | 33 |
Baseline characteristics
| Characteristic | FF/UMEC/VI 100/62.5/25 µg | BUD/FOR 400/12 µg | Total |
|---|---|---|---|
| Age, Continuous | 64.2 Years STANDARD_DEVIATION 8.56 | 63.7 Years STANDARD_DEVIATION 8.71 | 63.9 Years STANDARD_DEVIATION 8.64 |
| Race/Ethnicity, Customized Amrican Indian or Alaskan Native | 16 Participants | 19 Participants | 35 Participants |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 55 Participants | 49 Participants | 104 Participants |
| Race/Ethnicity, Customized Asian-South East Asian Heritag | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Mixed Race | 63 Participants | 62 Participants | 125 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White-Arabic/North African Heritage | 5 Participants | 8 Participants | 13 Participants |
| Race/Ethnicity, Customized White-White/Caucasina/Euorpean Heritage | 771 Participants | 759 Participants | 1530 Participants |
| Sex: Female, Male Female | 233 Participants | 236 Participants | 469 Participants |
| Sex: Female, Male Male | 678 Participants | 663 Participants | 1341 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 105 / 911 | 104 / 899 |
| serious Total, serious adverse events | 61 / 911 | 64 / 899 |
Outcome results
Primary
Change From Baseline in St George's Respiratory Questionnaire-Chronic Obstructive Pulmonary Disease (COPD; SGRQ) Total Score for COPD Participants at Week 24
The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 24 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions
Time frame: Baseline to Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in St George's Respiratory Questionnaire-Chronic Obstructive Pulmonary Disease (COPD; SGRQ) Total Score for COPD Participants at Week 24 | -6.6 Scores on a scale | Standard Error 0.45 |
| BUD/FOR 400/12 µg | Change From Baseline in St George's Respiratory Questionnaire-Chronic Obstructive Pulmonary Disease (COPD; SGRQ) Total Score for COPD Participants at Week 24 | -4.3 Scores on a scale | Standard Error 0.46 |
p-value: <0.00195% CI: [-3.5, -1]Mixed Model Repeated Measures
Primary
Change From Baseline in St George's Respiratory Questionnaire-COPD; SGRQ Total Score for COPD Participants at Week 52
The SGRQ-C is a disease-specific questionnaire designed to measure the impact of respiratory disease and its treatment on a COPD participant's health-related quality of life (HRQoL). SGRQ-C total score was converted to SGRQ total score (ranging from 0-100) according to manual. In addition to an overall summary (total) score, scores for the individual domains of Symptoms, Activity, and Impacts (each ranging from 0-100) are produced. A decrease in score indicated improvement in quality of life. The minimum clinically important difference (MCID) for this instrument is a 4-point improvement (decrease from Baseline). Baseline was defined as the value obtained predose on Day 1. Change from Baseline was calculated as total score at Week 52 minus the Baseline value. The analysis for SGRQ total score was performed using a MMRM method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions.
Time frame: Baseline to Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in St George's Respiratory Questionnaire-COPD; SGRQ Total Score for COPD Participants at Week 52 | -4.6 Scores on a scale | Standard Error 1.01 |
| BUD/FOR 400/12 µg | Change From Baseline in St George's Respiratory Questionnaire-COPD; SGRQ Total Score for COPD Participants at Week 52 | -1.9 Scores on a scale | Standard Error 1.03 |
p-value: 0.06595% CI: [-5.5, 0.2]Mixed Model Repeated Measures
Primary
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. ITT Population comprised of all randomized subjects excluding those who were randomized in error. Only participants with analyzable data at the given time point were analyzed.
Time frame: Baseline to Week 24
Population: ITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24 | 0.142 Liters (L) | Standard Error 0.0083 |
| BUD/FOR 400/12 µg | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24 | -0.029 Liters (L) | Standard Error 0.0085 |
p-value: <0.00195% CI: [0.148, 0.194]Mixed Model Repeated Measures
Primary
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 52
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 52 was defined as the FEV1 values obtained prior to morning dose of the study treatment. Baseline was defined as the value obtained predose (0 minutes) on Day 1. Change from Baseline was calculated as the pre-dose measurement at Week 24 minus the Baseline value. The analysis was performed using a mixed model repeated measures (MMRM) method including covariates of treatment group, smoking status (screening), geographical region, visit, baseline, baseline by visit and treatment by visit interactions. Extension Population: all participants in the ITT Population who were enrolled into the subset of participants with extension to 52 weeks.
Time frame: Baseline to Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 52 | 0.126 Liters (L) | Standard Error 0.017 |
| BUD/FOR 400/12 µg | Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 52 | -0.053 Liters (L) | Standard Error 0.0172 |
p-value: <0.00195% CI: [0.131, 0.226]Mixed Model Repeated Measures
Secondary
Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24
The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title).
Time frame: Baseline to Week 24
Population: ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 21-24, n=825,783 | -0.53 Scores on a scale | Standard Error 0.05 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 5-8, n=851,830 | -0.59 Scores on a scale | Standard Error 0.037 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 1-4, n=870,859 | -1.45 Scores on a scale | Standard Error 0.106 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 5-8, n=851,830 | -2.00 Scores on a scale | Standard Error 0.129 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 9-12, n=841,813 | -2.23 Scores on a scale | Standard Error 0.141 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 13-16, n=831,802 | -2.42 Scores on a scale | Standard Error 0.15 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 17-20, n=828,788 | -2.43 Scores on a scale | Standard Error 0.156 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 21-24, n=825,783 | -2.31 Scores on a scale | Standard Error 0.157 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 1-4, n=870,859 | -0.71 Scores on a scale | Standard Error 0.057 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 5-8, n=851,830 | -0.95 Scores on a scale | Standard Error 0.069 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 9-12, n=841,813 | -1.03 Scores on a scale | Standard Error 0.076 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 13-16, n=831, 802 | -1.11 Scores on a scale | Standard Error 0.08 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 17-20, n=828,788 | -1.10 Scores on a scale | Standard Error 0.084 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 21-24, n=825,783 | -1.07 Scores on a scale | Standard Error 0.085 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 1-4, n=870,859 | -0.41 Scores on a scale | Standard Error 0.031 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 9-12, n=841,813 | -0.67 Scores on a scale | Standard Error 0.041 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 13-16, n=831,802 | -0.74 Scores on a scale | Standard Error 0.043 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 17-20, n=828,788 | -0.77 Scores on a scale | Standard Error 0.045 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 21-24, n=825,783 | -0.72 Scores on a scale | Standard Error 0.046 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 1-4, n=870,859 | -0.33 Scores on a scale | Standard Error 0.034 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 5-8, n=851,830 | -0.46 Scores on a scale | Standard Error 0.042 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 9-12, n=841,813 | -0.54 Scores on a scale | Standard Error 0.046 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 13-16, n=831,802 | -0.58 Scores on a scale | Standard Error 0.048 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 17-20, n=828,788 | -0.57 Scores on a scale | Standard Error 0.05 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 9-12, n=841,813 | -0.20 Scores on a scale | Standard Error 0.047 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 13-16, n=831, 802 | -0.36 Scores on a scale | Standard Error 0.081 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 17-20, n=828,788 | -0.53 Scores on a scale | Standard Error 0.045 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 5-8, n=851,830 | -0.39 Scores on a scale | Standard Error 0.038 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 13-16, n=831,802 | -0.20 Scores on a scale | Standard Error 0.048 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 17-20, n=828,788 | -0.17 Scores on a scale | Standard Error 0.05 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 21-24, n=825,783 | -0.17 Scores on a scale | Standard Error 0.051 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 17-20, n=828,788 | -0.31 Scores on a scale | Standard Error 0.085 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 1-4, n=870,859 | -0.50 Scores on a scale | Standard Error 0.106 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 5-8, n=851,830 | -0.12 Scores on a scale | Standard Error 0.043 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 21-24, n=825,783 | -0.30 Scores on a scale | Standard Error 0.087 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 9-12, n=841,813 | -1.05 Scores on a scale | Standard Error 0.143 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 21-24, n=825,783 | -0.50 Scores on a scale | Standard Error 0.046 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 13-16, n=831,802 | -1.09 Scores on a scale | Standard Error 0.151 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 1-4, n=870,859 | -0.24 Scores on a scale | Standard Error 0.031 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 17-20, n=828,788 | -1.02 Scores on a scale | Standard Error 0.159 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 5-8, n=851,830 | -0.77 Scores on a scale | Standard Error 0.13 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Week 21-24, n=825,783 | -0.96 Scores on a scale | Standard Error 0.16 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 9-12, n=841,813 | -0.50 Scores on a scale | Standard Error 0.041 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 1-4, n=870,859 | -0.20 Scores on a scale | Standard Error 0.057 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Chest score, Week 1-4, n=870,859 | -0.06 Scores on a scale | Standard Error 0.035 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 5-8, n=851,830 | -0.26 Scores on a scale | Standard Error 0.07 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Cough, sputum score, Week 13-16, n=831,802 | -0.53 Scores on a scale | Standard Error 0.043 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean Exacerbations of Chronic Pulmonary Disease Tool (EXACT)-RS Scores up to Week 24 | Breathlessness score, Week 9-12, n=841,813 | -0.34 Scores on a scale | Standard Error 0.076 |
p-value: <0.00195% CI: [-1.25, -0.66]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-1.59, -0.87]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-1.57, -0.78]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-1.75, -0.91]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-1.85, -0.97]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-1.79, -0.91]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.67, -0.36]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.88, -0.5]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.9, -0.48]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.97, -0.52]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-1.03, -0.56]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-1.01, -0.54]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.26, -0.09]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.31, -0.1]Mixed Model Repeated Measures
p-value: 0.00495% CI: [-0.28, -0.05]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.34, -0.1]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.36, -0.11]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.35, -0.1]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.37, -0.18]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.46, -0.23]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.47, -0.21]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.51, -0.25]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.53, -0.26]Mixed Model Repeated Measures
p-value: <0.00195% CI: [-0.5, -0.22]Mixed Model Repeated Measures
Secondary
Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52
The EXACT-PRO is a 14 item instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. EXACT-RS consists of 11 items from the 14 item EXACT-PRO instrument and has a scoring range of 0-40. Three subscales are used to describe different symptoms; dyspnoea (range 0-17), cough and sputum (range 0-11) and chest symptoms (range 0-12). Baseline was defined as the mean value during the period between Visits 1 and 2. Mean scores were calculated for each four weekly period and change from Baseline was calculated as four weekly score minus the Baseline value. Four weekly intervals were analyzed using a MMRM method with covariates of treatment group, smoking status (screening), geographical region, time period, baseline, baseline by time period and treatment by time period interactions. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title).
Time frame: Baseline to Week 52
Population: Extension Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 1-4, n=205, 213 | -1.24 Scores on a scale | Standard Error 0.222 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 9-12, n=201, 206 | -2.18 Scores on a scale | Standard Error 0.298 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 21-24, n=202, 197 | -2.63 Scores on a scale | Standard Error 0.341 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 25-28, n=194, 186 | -2.48 Scores on a scale | Standard Error 0.349 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 37-40, n=185, 177 | -2.34 Scores on a scale | Standard Error 0.359 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 41-44, n=180, 174 | -2.30 Scores on a scale | Standard Error 0.363 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 45-48, n=180, 173 | -2.17 Scores on a scale | Standard Error 0.371 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 13-16, n=201, 204 | -1.19 Scores on a scale | Standard Error 0.175 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 29-32, n=192, 181 | -1.11 Scores on a scale | Standard Error 0.196 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 37-40, n=185, 177 | -1.13 Scores on a scale | Standard Error 0.203 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 45-48, n=180, 173 | -0.97 Scores on a scale | Standard Error 0.211 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 49-52, n=179, 171 | -0.96 Scores on a scale | Standard Error 0.207 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 9-12, n=201, 206 | -0.63 Scores on a scale | Standard Error 0.083 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 21-24, n=202, 197 | -0.83 Scores on a scale | Standard Error 0.098 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 21-24, n=202, 197 | -0.68 Scores on a scale | Standard Error 0.102 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 29-32, n=192, 181 | -0.55 Scores on a scale | Standard Error 0.107 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 33-36, n=187, 180 | -0.48 Scores on a scale | Standard Error 0.111 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 5-8, n=203, 208 | -1.97 Scores on a scale | Standard Error 0.265 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 13-16, n=201, 204 | -2.53 Scores on a scale | Standard Error 0.317 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 17-20, n=201, 199 | -2.64 Scores on a scale | Standard Error 0.342 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 29-32, n=192, 181 | -2.33 Scores on a scale | Standard Error 0.35 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 33-36, n=187, 180 | -2.12 Scores on a scale | Standard Error 0.367 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | EXACT-RS Scores, Week 49-52, n=179, 171 | -2.03 Scores on a scale | Standard Error 0.37 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 1-4, n=205, 213 | -0.64 Scores on a scale | Standard Error 0.12 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 5-8, n=203, 208 | -0.93 Scores on a scale | Standard Error 0.147 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 9-12, n=201, 206 | -1.05 Scores on a scale | Standard Error 0.167 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 17-20, n=201, 199 | -1.17 Scores on a scale | Standard Error 0.189 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 21-24, n=202, 197 | -1.13 Scores on a scale | Standard Error 0.19 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 25-28, n=194, 186 | -1.14 Scores on a scale | Standard Error 0.195 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 33-36, n=187, 180 | -1.08 Scores on a scale | Standard Error 0.204 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 41-44, n=180, 174 | -1.06 Scores on a scale | Standard Error 0.208 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 1-4, n=205, 213 | -0.34 Scores on a scale | Standard Error 0.065 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 5-8, n=203, 208 | -0.59 Scores on a scale | Standard Error 0.076 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 13-16, n=201, 204 | -0.73 Scores on a scale | Standard Error 0.088 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 17-20, n=201, 199 | -0.83 Scores on a scale | Standard Error 0.095 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 25-28, n=194, 186 | -0.73 Scores on a scale | Standard Error 0.097 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 29-32, n=192, 181 | -0.68 Scores on a scale | Standard Error 0.096 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 33-36, n=187, 180 | -0.56 Scores on a scale | Standard Error 0.099 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 37-40, n=185, 177 | -0.65 Scores on a scale | Standard Error 0.097 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 41-44, n=180, 174 | -0.66 Scores on a scale | Standard Error 0.101 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 45-48, n=180, 173 | -0.66 Scores on a scale | Standard Error 0.098 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 49-52, n=179, 171 | -0.61 Scores on a scale | Standard Error 0.1 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 1-4, n=205, 213 | -0.27 Scores on a scale | Standard Error 0.069 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 5-8, n=203, 208 | -0.46 Scores on a scale | Standard Error 0.084 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 9-12, n=201, 206 | -0.51 Scores on a scale | Standard Error 0.093 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 13-16, n=201, 204 | -0.61 Scores on a scale | Standard Error 0.097 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 17-20, n=201, 199 | -0.67 Scores on a scale | Standard Error 0.104 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 25-28, n=194, 186 | -0.63 Scores on a scale | Standard Error 0.105 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 37-40, n=185, 177 | -0.57 Scores on a scale | Standard Error 0.107 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 45-48, n=180, 173 | -0.57 Scores on a scale | Standard Error 0.113 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 41-44, n=180, 174 | -0.58 Scores on a scale | Standard Error 0.108 |
| FF/UMEC/VI 100/62.5/25 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 49-52, n=179, 171 | -0.49 Scores on a scale | Standard Error 0.115 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 17-20, n=201, 199 | -0.29 Scores on a scale | Standard Error 0.103 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 17-20, n=201, 199 | -0.50 Scores on a scale | Standard Error 0.186 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 13-16, n=201, 204 | -1.52 Scores on a scale | Standard Error 0.313 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 49-52, n=179, 171 | -0.08 Scores on a scale | Standard Error 0.115 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 21-24, n=202, 197 | -1.52 Scores on a scale | Standard Error 0.338 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 25-28, n=194, 186 | -0.21 Scores on a scale | Standard Error 0.104 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 49-52, n=179, 171 | -0.44 Scores on a scale | Standard Error 0.1 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 37-40, n=185, 177 | -1.11 Scores on a scale | Standard Error 0.358 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 33-36, n=187, 180 | -0.14 Scores on a scale | Standard Error 0.203 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 29-32, n=192, 181 | -0.16 Scores on a scale | Standard Error 0.107 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 45-48, n=180, 173 | -0.64 Scores on a scale | Standard Error 0.371 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | EXACT-RS Scores, Week 49-52, n=179, 171 | -0.61 Scores on a scale | Standard Error 0.37 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 1-4, n=205, 213 | -0.31 Scores on a scale | Standard Error 0.118 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 45-48, n=180, 173 | -0.11 Scores on a scale | Standard Error 0.211 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 21-24, n=202, 197 | -0.50 Scores on a scale | Standard Error 0.188 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 25-28, n=194, 186 | -0.38 Scores on a scale | Standard Error 0.194 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 49-52, n=179, 171 | -0.08 Scores on a scale | Standard Error 0.207 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 29-32, n=192, 181 | -0.26 Scores on a scale | Standard Error 0.194 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 1-4, n=205, 213 | -0.09 Scores on a scale | Standard Error 0.068 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 37-40, n=185, 177 | -0.37 Scores on a scale | Standard Error 0.202 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 41-44, n=180, 174 | -0.24 Scores on a scale | Standard Error 0.208 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 1-4, n=205, 213 | -0.32 Scores on a scale | Standard Error 0.064 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 33-36, n=187, 180 | -0.08 Scores on a scale | Standard Error 0.111 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 5-8, n=203, 208 | -0.44 Scores on a scale | Standard Error 0.074 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 9-12, n=201, 206 | -0.52 Scores on a scale | Standard Error 0.082 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 5-8, n=203, 208 | -0.13 Scores on a scale | Standard Error 0.082 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 41-44, n=180, 174 | -0.41 Scores on a scale | Standard Error 0.102 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 45-48, n=180, 173 | -0.39 Scores on a scale | Standard Error 0.099 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 13-16, n=201, 204 | -0.62 Scores on a scale | Standard Error 0.087 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 21-24, n=202, 197 | -0.30 Scores on a scale | Standard Error 0.101 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 41-44, n=180, 174 | -0.16 Scores on a scale | Standard Error 0.108 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 17-20, n=201, 199 | -0.73 Scores on a scale | Standard Error 0.094 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 1-4, n=205, 213 | -0.72 Scores on a scale | Standard Error 0.218 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 21-24, n=202, 197 | -0.71 Scores on a scale | Standard Error 0.097 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 5-8, n=203, 208 | -0.90 Scores on a scale | Standard Error 0.26 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 9-12, n=201, 206 | -1.21 Scores on a scale | Standard Error 0.294 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 9-12, n=201, 206 | -0.24 Scores on a scale | Standard Error 0.092 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 25-28, n=194, 186 | -0.57 Scores on a scale | Standard Error 0.097 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 17-20, n=201, 199 | -1.53 Scores on a scale | Standard Error 0.338 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 25-28, n=194, 186 | -1.16 Scores on a scale | Standard Error 0.347 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 37-40, n=185, 177 | -0.20 Scores on a scale | Standard Error 0.107 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 29-32, n=192, 181 | -0.90 Scores on a scale | Standard Error 0.349 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 29-32, n=192, 181 | -0.48 Scores on a scale | Standard Error 0.096 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 33-36, n=187, 180 | -0.62 Scores on a scale | Standard Error 0.366 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Week 41-44, n=180, 174 | -0.81 Scores on a scale | Standard Error 0.362 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 13-16, n=201, 204 | -0.31 Scores on a scale | Standard Error 0.095 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 33-36, n=187, 180 | -0.40 Scores on a scale | Standard Error 0.099 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Chest scores, Week 45-48, n=180, 173 | -0.13 Scores on a scale | Standard Error 0.113 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 5-8, n=203, 208 | -0.32 Scores on a scale | Standard Error 0.145 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Cough and sputum scores, Week 37-40, n=185, 177 | -0.54 Scores on a scale | Standard Error 0.097 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 9-12, n=201, 206 | -0.44 Scores on a scale | Standard Error 0.164 |
| BUD/FOR 400/12 µg | Assessment of Respiratory Symptoms by Change From Baseline in 4-weekly Mean EXACT-RS Scores up to Week 52 | Breathlessness scores, Week 13-16, n=201, 204 | -0.57 Scores on a scale | Standard Error 0.173 |
p-value: 0.09495% CI: [-1.13, 0.09]Mixed Model Repeated Measures
p-value: 0.00495% CI: [-1.8, -0.34]Mixed Model Repeated Measures
p-value: 0.02295% CI: [-1.79, -0.14]Mixed Model Repeated Measures
p-value: 0.02495% CI: [-1.88, -0.13]Mixed Model Repeated Measures
p-value: 0.02195% CI: [-2.06, -0.17]Mixed Model Repeated Measures
p-value: 0.02295% CI: [-2.05, -0.16]Mixed Model Repeated Measures
p-value: 0.00895% CI: [-2.29, -0.35]Mixed Model Repeated Measures
p-value: 0.00495% CI: [-2.4, -0.46]Mixed Model Repeated Measures
p-value: 0.00495% CI: [-2.52, -0.48]Mixed Model Repeated Measures
p-value: 0.01695% CI: [-2.22, -0.23]Mixed Model Repeated Measures
p-value: 0.0495% CI: [-2.5, -0.48]Mixed Model Repeated Measures
p-value: 0.00795% CI: [-2.56, -0.5]Mixed Model Repeated Measures
p-value: 0.00795% CI: [-2.45, -0.39]Mixed Model Repeated Measures
p-value: 0.05195% CI: [-0.66, 0]Mixed Model Repeated Measures
p-value: 0.00395% CI: [-1.02, -0.2]Mixed Model Repeated Measures
p-value: 0.0195% CI: [-1.07, -0.15]Mixed Model Repeated Measures
p-value: 0.01395% CI: [-1.1, -0.13]Mixed Model Repeated Measures
p-value: 0.01295% CI: [-1.19, -0.15]Mixed Model Repeated Measures
p-value: 0.01895% CI: [-1.16, -0.11]Mixed Model Repeated Measures
p-value: 0.00695% CI: [-1.3, -0.21]Mixed Model Repeated Measures
p-value: 0.00295% CI: [-1.4, -0.31]Mixed Model Repeated Measures
p-value: 0.00195% CI: [-1.51, -0.38]Mixed Model Repeated Measures
p-value: 0.00895% CI: [-1.32, -0.2]Mixed Model Repeated Measures
p-value: 0.00695% CI: [-1.4, -0.24]Mixed Model Repeated Measures
p-value: 0.00495% CI: [-1.44, -0.27]Breathlessness score, Week 41-44
p-value: 0.00395% CI: [-1.45, -0.3]Mixed Model Repeated Measures
p-value: 0.8495% CI: [-0.2, 0.16]Mixed Model Repeated Measures
p-value: 0.16795% CI: [-0.36, -0.06]Mixed Model Repeated Measures
p-value: 0.35995% CI: [-0.34, 0.12]Mixed Model Repeated Measures
p-value: 0.3695% CI: [-0.36, 0.13]Mixed Model Repeated Measures
p-value: 0.4995% CI: [-0.36, 0.17]Mixed Model Repeated Measures
p-value: 0.38895% CI: [-0.39, 0.15]Mixed Model Repeated Measures
p-value: 0.21895% CI: [-0.44, 0.1]Mixed Model Repeated Measures
p-value: 0.13895% CI: [-0.47, 0.07]Mixed Model Repeated Measures
p-value: 0.23995% CI: [-0.44, 0.11]Mixed Model Repeated Measures
p-value: 0.41795% CI: [-0.38, 0.16]Mixed Model Repeated Measures
p-value: 0.07895% CI: [-0.54, 0.03]Mixed Model Repeated Measures
p-value: 0.05895% CI: [-0.54, 0.01]Mixed Model Repeated Measures
p-value: 0.23195% CI: [-0.45, 0.11]Mixed Model Repeated Measures
p-value: 0.06895% CI: [-0.37, 0.01]Mixed Model Repeated Measures
p-value: 0.00695% CI: [-0.56, -0.09]Mixed Model Repeated Measures
p-value: 0.04295% CI: [-0.53, -0.01]Mixed Model Repeated Measures
p-value: 0.02795% CI: [-0.57, -0.03]Mixed Model Repeated Measures
p-value: 0.0195% CI: [-0.67, -0.09]Mixed Model Repeated Measures
p-value: 0.0195% CI: [-0.66, -0.09]Mixed Model Repeated Measures
95% CI: [-0.7, -0.12]Mixed Model Repeated Measures
p-value: 0.01195% CI: [-0.68, -0.09]Mixed Model Repeated Measures
p-value: 0.01195% CI: [-0.71, -0.09]Mixed Model Repeated Measures
p-value: 0.01495% CI: [-0.67, -0.07]Mixed Model Repeated Measures
p-value: 0.00795% CI: [-0.72, -0.12]Mixed Model Repeated Measures
p-value: 0.00695% CI: [-0.76, -0.13]Mixed Model Repeated Measures
p-value: 0.01395% CI: [-0.73, -0.09]Mixed Model Repeated Measures
Secondary
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24
Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12 and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, ALT, n=838,785 | 1.4 International units per liter (IU/L) | Standard Deviation 10.81 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, ALT, n=887,864 | 3.0 International units per liter (IU/L) | Standard Deviation 11.99 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, AST, n=835,785 | 1.1 International units per liter (IU/L) | Standard Deviation 10.3 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, AST, n=887,866 | 3.2 International units per liter (IU/L) | Standard Deviation 12.61 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, ALP, n=839,787 | 1.1 International units per liter (IU/L) | Standard Deviation 15.42 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, ALP, n=888,866 | 4.3 International units per liter (IU/L) | Standard Deviation 16.46 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, GGT, n=888,866 | 7.5 International units per liter (IU/L) | Standard Deviation 42.66 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, Creatine Kinase, n=888,866 | 20.6 International units per liter (IU/L) | Standard Deviation 138.17 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, GGT, n=839,787 | 3.4 International units per liter (IU/L) | Standard Deviation 31.65 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, Creatine Kinase, n=839,787 | -3.9 International units per liter (IU/L) | Standard Deviation 106.48 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, GGT, n=839,787 | 0.5 International units per liter (IU/L) | Standard Deviation 21.84 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, ALT, n=838,785 | 3.8 International units per liter (IU/L) | Standard Deviation 69.15 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, ALT, n=887,864 | 5.5 International units per liter (IU/L) | Standard Deviation 66.01 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, GGT, n=888,866 | 4.7 International units per liter (IU/L) | Standard Deviation 27.76 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, AST, n=835,785 | 4.0 International units per liter (IU/L) | Standard Deviation 86.63 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, Creatine Kinase, n=839,787 | -3.4 International units per liter (IU/L) | Standard Deviation 191.25 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, AST, n=887,866 | 5.6 International units per liter (IU/L) | Standard Deviation 82.66 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Week 24, ALP, n=839,787 | -2.8 International units per liter (IU/L) | Standard Deviation 12.47 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, Creatine Kinase, n=888,866 | 20.6 International units per liter (IU/L) | Standard Deviation 185.06 |
| BUD/FOR 400/12 µg | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Aminotransferase (GGT), Alkaline Phosphatase (ALP), and Creatine Kinase at Week 24 | Maximum post BL, ALP, n=888,866 | 0.8 International units per liter (IU/L) | Standard Deviation 11.96 |
Secondary
Change From Baseline in Albumin and Protein at Week 24
Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12 and Week 24. Change from Baseline (BL) was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). The maximum post BL values have been presented. Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 24 | Week 24, Albumin, n=839,787 | -0.7 g/L | Standard Deviation 2.55 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 24 | Maximum post BL, Albumin, n=888,866 | 0.1 g/L | Standard Deviation 2.36 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 24 | Week 24, Protein, n=839,787 | -0.6 g/L | Standard Deviation 3.7 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 24 | Maximum post BL, Protein, n=888,866 | 0.4 g/L | Standard Deviation 3.42 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 24 | Maximum post BL, Protein, n=888,866 | 0.1 g/L | Standard Deviation 3.43 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 24 | Week 24, Albumin, n=839,787 | -0.5 g/L | Standard Deviation 2.41 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 24 | Week 24, Protein, n=839,787 | -1.0 g/L | Standard Deviation 3.64 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 24 | Maximum post BL, Albumin, n=888,866 | 0.2 g/L | Standard Deviation 2.24 |
Secondary
Change From Baseline in Albumin and Protein at Week 52
Blood samples were collected for the measurement of albumin and protein at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 52 | Week 52, Albumin, n=181,174 | -0.8 g/L | Standard Deviation 2.77 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 52 | Maximum post BL,Albumin, n=207,214 | 0.4 g/L | Standard Deviation 2.45 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 52 | Week 52, Protein, n=181,174 | -1.1 g/L | Standard Deviation 4.04 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Albumin and Protein at Week 52 | Maximum post BL, Protein, n=207,214 | 0.6 g/L | Standard Deviation 3.57 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 52 | Maximum post BL, Protein, n=207,214 | 0.0 g/L | Standard Deviation 3.3 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 52 | Week 52, Albumin, n=181,174 | -0.7 g/L | Standard Deviation 2.64 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 52 | Week 52, Protein, n=181,174 | -1.6 g/L | Standard Deviation 3.86 |
| BUD/FOR 400/12 µg | Change From Baseline in Albumin and Protein at Week 52 | Maximum post BL,Albumin, n=207,214 | 0.2 g/L | Standard Deviation 2.25 |
Secondary
Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52
Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT at Baseline, Week 12, Week 24 and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, Creatine Kinase, n=181,174 | 6.1 International units per liter (IU/L) | Standard Deviation 68.48 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, AST, n=180,174 | 1.7 International units per liter (IU/L) | Standard Deviation 9.72 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, ALP, n=181,174 | 1.7 International units per liter (IU/L) | Standard Deviation 13.77 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, ALP, n=207,214 | 6.7 International units per liter (IU/L) | Standard Deviation 12.84 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, GGT, n=181,174 | 0.2 International units per liter (IU/L) | Standard Deviation 28.77 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, GGT, n=207,214 | 7.7 International units per liter (IU/L) | Standard Deviation 31.33 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, Creatine Kinase, n=207,214 | 39.9 International units per liter (IU/L) | Standard Deviation 79.71 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, ALT, n=181,173 | 1.7 International units per liter (IU/L) | Standard Deviation 10.64 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, ALT, n=207,212 | 5.4 International units per liter (IU/L) | Standard Deviation 15.45 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, AST, n=207,214 | 5.5 International units per liter (IU/L) | Standard Deviation 15.55 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, ALT, n=207,212 | 4.5 International units per liter (IU/L) | Standard Deviation 12.84 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, GGT, n=207,214 | 8.9 International units per liter (IU/L) | Standard Deviation 34.98 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, AST, n=180,174 | 0.8 International units per liter (IU/L) | Standard Deviation 11.16 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, AST, n=207,214 | 3.7 International units per liter (IU/L) | Standard Deviation 11.65 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, Creatine Kinase, n=181,174 | 16.7 International units per liter (IU/L) | Standard Deviation 97.17 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, ALP, n=181,174 | -2.7 International units per liter (IU/L) | Standard Deviation 10.83 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, ALT, n=181,173 | 1.3 International units per liter (IU/L) | Standard Deviation 12.38 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, ALP, n=207,214 | 1.2 International units per liter (IU/L) | Standard Deviation 11.73 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Maximum post BL, Creatine Kinase, n=207,214 | 46.9 International units per liter (IU/L) | Standard Deviation 90.78 |
| BUD/FOR 400/12 µg | Change From Baseline in ALT, AST, GGT, ALP, and Creatine Kinase at Week 52 | Week 52, GGT, n=181,174 | 0.2 International units per liter (IU/L) | Standard Deviation 26.86 |
Secondary
Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24
Hematology laboratory assessments included basophils, eosinophils, lymphocytes, monocytes, neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a repeat test). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Basophils, n=876,853 | 0.005 10^9 cells/Liter(L) | Standard Deviation 0.0211 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Monocytes, n=876,853 | 0.040 10^9 cells/Liter(L) | Standard Deviation 0.1985 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Platelets, n=810,759 | -0.7 10^9 cells/Liter(L) | Standard Deviation 43.12 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Neutrophils, n=817,761 | 0.071 10^9 cells/Liter(L) | Standard Deviation 1.7682 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Neutrophils, n=876,853 | 0.481 10^9 cells/Liter(L) | Standard Deviation 1.8761 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Eosinophils, n=817, 761 | -0.008 10^9 cells/Liter(L) | Standard Deviation 0.1926 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Leukocytes, n=819,761 | 0.06 10^9 cells/Liter(L) | Standard Deviation 1.847 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Basophils, n=817,761 | -0.001 10^9 cells/Liter(L) | Standard Deviation 0.0217 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Leukocytes, n=877,853 | 0.52 10^9 cells/Liter(L) | Standard Deviation 1.94 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maxmium post BL, Eosinophils, n=876,853 | 0.034 10^9 cells/Liter(L) | Standard Deviation 0.1941 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Platelets, n=871,846 | 10.8 10^9 cells/Liter(L) | Standard Deviation 42.5 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Lymphocytes, n=817,761 | 0.002 10^9 cells/Liter(L) | Standard Deviation 0.5311 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Lymphocytes, n=876,853 | 0.187 10^9 cells/Liter(L) | Standard Deviation 0.5468 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Category title 5. Week 24, Monocytes, n=817,761 | -0.006 10^9 cells/Liter(L) | Standard Deviation 0.1977 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Lymphocytes, n=876,853 | 0.150 10^9 cells/Liter(L) | Standard Deviation 0.5767 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Neutrophils, n=817,761 | 0.142 10^9 cells/Liter(L) | Standard Deviation 1.8552 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Platelets, n=810,759 | -0.7 10^9 cells/Liter(L) | Standard Deviation 44.26 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Lymphocytes, n=817,761 | -0.023 10^9 cells/Liter(L) | Standard Deviation 0.5669 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Basophils, n=817,761 | -0.001 10^9 cells/Liter(L) | Standard Deviation 0.0204 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Basophils, n=876,853 | 0.005 10^9 cells/Liter(L) | Standard Deviation 0.0206 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Eosinophils, n=817, 761 | -0.015 10^9 cells/Liter(L) | Standard Deviation 0.1926 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maxmium post BL, Eosinophils, n=876,853 | 0.019 10^9 cells/Liter(L) | Standard Deviation 0.1952 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Category title 5. Week 24, Monocytes, n=817,761 | 0.004 10^9 cells/Liter(L) | Standard Deviation 0.2125 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Monocytes, n=876,853 | 0.048 10^9 cells/Liter(L) | Standard Deviation 0.2069 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Neutrophils, n=876,853 | 0.649 10^9 cells/Liter(L) | Standard Deviation 1.9143 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Week 24, Leukocytes, n=819,761 | 0.11 10^9 cells/Liter(L) | Standard Deviation 1.915 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Leukocytes, n=877,853 | 0.64 10^9 cells/Liter(L) | Standard Deviation 1.947 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 24 | Maximum post BL, Platelets, n=871,846 | 10.2 10^9 cells/Liter(L) | Standard Deviation 45.46 |
Secondary
Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52
Hematology laboratory assessments included Basophils, eosinophils, lymphocytes, monocytes,neutrophils, total neutrophil, leukocytes, and platelets; parameters were measured at Baseline (BL), Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Lymphocytes, n=202,212 | 0.325 10^9 cells/L | Standard Deviation 0.6299 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Monocytes, n=205,212 | 0.075 10^9 cells/L | Standard Deviation 0.2359 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Neutrophils, n=205,212 | 0.923 10^9 cells/L | Standard Deviation 2.1444 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Leukocytes, n=205,212 | 0.97 10^9 cells/L | Standard Deviation 2.163 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Basophils, n=168,166 | 0.002 10^9 cells/L | Standard Deviation 0.0203 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Basophils, n=205,212 | 0.011 10^9 cells/L | Standard Deviation 0.0196 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Eosinophils, n=205,212 | 0.074 10^9 cells/L | Standard Deviation 0.246 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Monocytes, n=168,166 | 0.025 10^9 cells/L | Standard Deviation 0.2382 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Neutrophils, n=168,166 | 0.246 10^9 cells/L | Standard Deviation 2.1768 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Leukocytes, n=168,166 | 0.33 10^9 cells/L | Standard Deviation 2.243 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Platelets, n=170,166 | -1.8 10^9 cells/L | Standard Deviation 39.96 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Platelets, n=203,210 | 13.6 10^9 cells/L | Standard Deviation 40.57 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Lymphocytes, n=168,166 | 0.060 10^9 cells/L | Standard Deviation 0.685 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Eosinophils, n=168,166 | 0.002 10^9 cells/L | Standard Deviation 0.1819 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Leukocytes, n=205,212 | 0.87 10^9 cells/L | Standard Deviation 2.168 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Monocytes, n=168,166 | 0.028 10^9 cells/L | Standard Deviation 0.2164 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Eosinophils, n=205,212 | 0.057 10^9 cells/L | Standard Deviation 0.2884 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Monocytes, n=205,212 | 0.072 10^9 cells/L | Standard Deviation 0.2123 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Neutrophils, n=168,166 | -0.163 10^9 cells/L | Standard Deviation 2.3222 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Platelets, n=203,210 | 13.9 10^9 cells/L | Standard Deviation 51.61 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Neutrophils, n=205,212 | 0.835 10^9 cells/L | Standard Deviation 2.1223 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Platelets, n=170,166 | -2.7 10^9 cells/L | Standard Deviation 49.22 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Lymphocytes, n=202,212 | 0.295 10^9 cells/L | Standard Deviation 0.591 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Lymphocytes, n=168,166 | -0.027 10^9 cells/L | Standard Deviation 0.5714 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Basophils, n=168,166 | 0.003 10^9 cells/L | Standard Deviation 0.0241 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Leukocytes, n=168,166 | -0.17 10^9 cells/L | Standard Deviation 2.387 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Maximum post BL, Basophils, n=205,212 | 0.010 10^9 cells/L | Standard Deviation 0.0226 |
| BUD/FOR 400/12 µg | Change From Baseline in Basophils, Eosinophils, Monocytes, Neutrophils, Leukocytes, Lymphocytes, and Platelets at Week 52 | Week 52, Eosinophils, n=168,166 | -0.011 10^9 cells/L | Standard Deviation 0.2567 |
Secondary
Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24
Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Week 24, Creatinine, n=839,787 | 1.05 Micromoles per liter | Standard Deviation 9.816 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Maximum post BL, Bilirubin, n=888,865 | 1.1 Micromoles per liter | Standard Deviation 4.09 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Maximum post BL, Creatinine, n=888,866 | 4.12 Micromoles per liter | Standard Deviation 9.711 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Week 24, Urate, n=839,787 | 2.8 Micromoles per liter | Standard Deviation 60.87 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Maximum post BL, Urate, n=888,866 | 23.7 Micromoles per liter | Standard Deviation 58.64 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Week 24, Bilirubin, n=839,786 | -0.2 Micromoles per liter | Standard Deviation 3.88 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Maximum post BL, Urate, n=888,866 | 21.9 Micromoles per liter | Standard Deviation 59.2 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Week 24, Bilirubin, n=839,786 | 0.1 Micromoles per liter | Standard Deviation 3.77 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Maximum post BL, Bilirubin, n=888,865 | 1.2 Micromoles per liter | Standard Deviation 3.67 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Week 24, Creatinine, n=839,787 | 1.14 Micromoles per liter | Standard Deviation 9.58 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Maximum post BL, Creatinine, n=888,866 | 3.99 Micromoles per liter | Standard Deviation 9.509 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 24 | Week 24, Urate, n=839,787 | 1.7 Micromoles per liter | Standard Deviation 62.96 |
Secondary
Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52
Blood samples were collected for the measurement of bilirubin, creatinine, and urate at Baseline, Week 12, Week 24, and Week 52 of the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat).
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Maximum post BL, Creatinine, n=207,214 | 6.99 Micromoles per liter | Standard Deviation 11.425 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Week 52, Creatinine, n=181,174 | 2.95 Micromoles per liter | Standard Deviation 11.663 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Week 52, Urate, n=181,174 | 3.6 Micromoles per liter | Standard Deviation 60.92 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Maximum post BL, Urate, n=207,214 | 42.0 Micromoles per liter | Standard Deviation 62.06 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Week 52, Bilirubin, n=181,174 | 0.3 Micromoles per liter | Standard Deviation 3.41 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Maximum post BL, Bilirubin, n=207,214 | 2.0 Micromoles per liter | Standard Deviation 3.88 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Week 52, Bilirubin, n=181,174 | 0.1 Micromoles per liter | Standard Deviation 3.94 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Maximum post BL, Bilirubin, n=207,214 | 2.3 Micromoles per liter | Standard Deviation 4.28 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Maximum post BL, Urate, n=207,214 | 40.0 Micromoles per liter | Standard Deviation 63.47 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Maximum post BL, Creatinine, n=207,214 | 6.00 Micromoles per liter | Standard Deviation 11.392 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Week 52, Creatinine, n=181,174 | 1.28 Micromoles per liter | Standard Deviation 11.563 |
| BUD/FOR 400/12 µg | Change From Baseline in Bilirubin, Creatinine, and Urate at Week 52 | Week 52, Urate, n=181,174 | 3.9 Micromoles per liter | Standard Deviation 64.85 |
Secondary
Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) and PR Interval at Week 24
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading.
Time frame: Baseline and Week 24
Population: ITT population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) and PR Interval at Week 24 | QTcF, n=840,787 | 2.5 Milliseconds (msec) | Standard Error 0.56 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) and PR Interval at Week 24 | PR, n=812,766 | -0.1 Milliseconds (msec) | Standard Error 0.54 |
| BUD/FOR 400/12 µg | Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) and PR Interval at Week 24 | QTcF, n=840,787 | 0.6 Milliseconds (msec) | Standard Error 0.58 |
| BUD/FOR 400/12 µg | Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) and PR Interval at Week 24 | PR, n=812,766 | 0.5 Milliseconds (msec) | Standard Error 0.56 |
p-value: 0.02395% CI: [0.3, 3.4]Mixed Model Repeated Measures
p-value: 0.47195% CI: [-2.1, 1]Mixed Model Repeated Measures
Secondary
Change From Baseline in Erythrocytes at Week 24
Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 24. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Erythrocytes at Week 24 | Week 24, n=822,769 | -0.02 10^12 cells/L | Standard Deviation 0.292 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Erythrocytes at Week 24 | Maximum post BL, n=880,857 | 0.06 10^12 cells/L | Standard Deviation 0.27 |
| BUD/FOR 400/12 µg | Change From Baseline in Erythrocytes at Week 24 | Week 24, n=822,769 | -0.04 10^12 cells/L | Standard Deviation 0.294 |
| BUD/FOR 400/12 µg | Change From Baseline in Erythrocytes at Week 24 | Maximum post BL, n=880,857 | 0.04 10^12 cells/L | Standard Deviation 0.273 |
Secondary
Change From Baseline in Erythrocytes at Week 52
Hematology laboratory assessments included erythrocytes and was measured at Baseline, Week 12 and Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated by subtracting the Baseline value from the individual post-dose value at Week 52. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Erythrocytes at Week 52 | Week 52, n=174,170 | 0.02 10^12 cells/L | Standard Deviation 0.282 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Erythrocytes at Week 52 | Maximum post BL, n=206,212 | 0.11 10^12 cells/L | Standard Deviation 0.261 |
| BUD/FOR 400/12 µg | Change From Baseline in Erythrocytes at Week 52 | Week 52, n=174,170 | 0.00 10^12 cells/L | Standard Deviation 0.313 |
| BUD/FOR 400/12 µg | Change From Baseline in Erythrocytes at Week 52 | Maximum post BL, n=206,212 | 0.07 10^12 cells/L | Standard Deviation 0.289 |
Secondary
Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24
Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, phophate, potassium, sodium, and urea at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Sodium, n=837,787 | -0.3 Millimoles per liter (mmol/L) | Standard Deviation 2.35 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Calcium, n=835,785 | -0.016 Millimoles per liter (mmol/L) | Standard Deviation 0.0887 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Phosphate, n=839,787 | -0.028 Millimoles per liter (mmol/L) | Standard Deviation 0.2373 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Calcium, n=887,866 | 0.013 Millimoles per liter (mmol/L) | Standard Deviation 0.0817 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Sodium, n=888,866 | 0.6 Millimoles per liter (mmol/L) | Standard Deviation 2.15 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Chloride, n=838,787 | -0.4 Millimoles per liter (mmol/L) | Standard Deviation 2.76 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Potassium, n=887,866 | 0.18 Millimoles per liter (mmol/L) | Standard Deviation 0.428 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Chloride, n=888,866 | 0.9 Millimoles per liter (mmol/L) | Standard Deviation 2.53 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, CO2, n=835,785 | -0.6 Millimoles per liter (mmol/L) | Standard Deviation 2.54 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Urea, n=839,787 | 0.08 Millimoles per liter (mmol/L) | Standard Deviation 1.591 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, CO2, n=835,785 | 0.0 Millimoles per liter (mmol/L) | Standard Deviation 2.38 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Glucose, n=887,866 | 0.53 Millimoles per liter (mmol/L) | Standard Deviation 1.506 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Glucose, n=839,787 | 0.12 Millimoles per liter (mmol/L) | Standard Deviation 1.433 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Potassium, n=834,785 | 0.04 Millimoles per liter (mmol/L) | Standard Deviation 0.457 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Phosphate, n=888,866 | 0.039 Millimoles per liter (mmol/L) | Standard Deviation 0.231 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Urea, n=888,866 | 0.68 Millimoles per liter (mmol/L) | Standard Deviation 1.601 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Urea, n=888,866 | 0.64 Millimoles per liter (mmol/L) | Standard Deviation 1.604 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Glucose, n=839,787 | -0.00 Millimoles per liter (mmol/L) | Standard Deviation 1.449 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Glucose, n=887,866 | 0.37 Millimoles per liter (mmol/L) | Standard Deviation 1.463 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Potassium, n=834,785 | -0.03 Millimoles per liter (mmol/L) | Standard Deviation 0.456 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Potassium, n=887,866 | 0.13 Millimoles per liter (mmol/L) | Standard Deviation 0.417 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Phosphate, n=839,787 | -0.029 Millimoles per liter (mmol/L) | Standard Deviation 0.2728 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Phosphate, n=888,866 | 0.043 Millimoles per liter (mmol/L) | Standard Deviation 0.2576 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Sodium, n=837,787 | -0.2 Millimoles per liter (mmol/L) | Standard Deviation 2.38 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Sodium, n=888,866 | 0.7 Millimoles per liter (mmol/L) | Standard Deviation 2.22 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Urea, n=839,787 | 0.04 Millimoles per liter (mmol/L) | Standard Deviation 1.549 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Chloride, n=888,866 | 0.6 Millimoles per liter (mmol/L) | Standard Deviation 2.35 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Calcium, n=835,785 | -0.014 Millimoles per liter (mmol/L) | Standard Deviation 0.0931 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, Calcium, n=887,866 | 0.012 Millimoles per liter (mmol/L) | Standard Deviation 0.0868 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, Chloride, n=838,787 | -0.7 Millimoles per liter (mmol/L) | Standard Deviation 2.6 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Week 24, CO2, n=835,785 | -0.0 Millimoles per liter (mmol/L) | Standard Deviation 2.61 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, Carbon Dioxide (CO2), Chloride, Phosphate, Potassium, Sodium, and Urea at Week 24 | Maximum post BL, CO2, n=835,785 | 0.5 Millimoles per liter (mmol/L) | Standard Deviation 2.48 |
Secondary
Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52
Blood samples were collected for the measurement of Glucose, calcium, CO2, chloride, magnesium, phophate, potassium, sodium, and urea at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, CO2, n=180,174 | -1.2 Mmol/L | Standard Deviation 2.46 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Potassium, n=207,214 | 0.29 Mmol/L | Standard Deviation 0.456 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,CO2, n=207,214 | -0.2 Mmol/L | Standard Deviation 2.26 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Phosphate, n=181,174 | -0.003 Mmol/L | Standard Deviation 0.1645 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Calcium, n=207,214 | 0.026 Mmol/L | Standard Deviation 0.0849 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Phosphate, n=207,214 | 0.109 Mmol/L | Standard Deviation 0.1551 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Glucose, n=181,174 | 0.31 Mmol/L | Standard Deviation 1.538 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Sodium, n=181,174 | -0.2 Mmol/L | Standard Deviation 2.34 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Chloride, n=207,214 | 1.4 Mmol/L | Standard Deviation 2.63 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Sodium, n=207,214 | 1.1 Mmol/L | Standard Deviation 2.13 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Urea, n=181,174 | 0.16 Mmol/L | Standard Deviation 1.625 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Glucose, n=207,214 | 0.92 Mmol/L | Standard Deviation 1.683 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL, Urea, n=207,214 | 1.06 Mmol/L | Standard Deviation 1.755 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Chloride, n=181,174 | -0.1 Mmol/L | Standard Deviation 3 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Potassium, n=180,174 | -0.02 Mmol/L | Standard Deviation 0.443 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Calcium, n=180,174 | -0.033 Mmol/L | Standard Deviation 0.0943 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Sodium, n=207,214 | 1.1 Mmol/L | Standard Deviation 2.22 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Calcium, n=180,174 | -0.040 Mmol/L | Standard Deviation 0.0968 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Calcium, n=207,214 | 0.008 Mmol/L | Standard Deviation 0.0868 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Chloride, n=181,174 | -0.2 Mmol/L | Standard Deviation 2.71 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Chloride, n=207,214 | 1.3 Mmol/L | Standard Deviation 2.39 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,CO2, n=207,214 | 0.3 Mmol/L | Standard Deviation 2.28 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Glucose, n=181,174 | 0.22 Mmol/L | Standard Deviation 1.546 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Glucose, n=207,214 | 0.63 Mmol/L | Standard Deviation 1.738 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Potassium, n=180,174 | -0.10 Mmol/L | Standard Deviation 0.454 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Potassium, n=207,214 | 0.20 Mmol/L | Standard Deviation 0.418 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Phosphate, n=181,174 | 0.005 Mmol/L | Standard Deviation 0.18 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL,Phosphate, n=207,214 | 0.110 Mmol/L | Standard Deviation 0.177 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Sodium, n=181,174 | -0.1 Mmol/L | Standard Deviation 2.51 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, Urea, n=181,174 | 0.12 Mmol/L | Standard Deviation 1.553 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Maximum post BL, Urea, n=207,214 | 1.08 Mmol/L | Standard Deviation 1.629 |
| BUD/FOR 400/12 µg | Change From Baseline in Glucose, Calcium, CO2, Chloride, Magnesium, Phosphate, Potassium, Sodium, and Urea at Week 52 | Week 52, CO2, n=180,174 | -1.0 Mmol/L | Standard Deviation 2.58 |
Secondary
Change From Baseline in Heart Rate at Week 24
A single 12-lead electrocardiogram (ECG) and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading.
Time frame: Baseline and Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Heart Rate at Week 24 | -1.1 Beats per minute (Bpm) | Standard Deviation 11.51 |
| BUD/FOR 400/12 µg | Change From Baseline in Heart Rate at Week 24 | -1.2 Beats per minute (Bpm) | Standard Deviation 10.91 |
Secondary
Change From Baseline in Heart Rate at Week 52
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG heart rate was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading.
Time frame: Baseline and Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Heart Rate at Week 52 | 0.2 Bpm | Standard Deviation 11.3 |
| BUD/FOR 400/12 µg | Change From Baseline in Heart Rate at Week 52 | -1.0 Bpm | Standard Deviation 10.77 |
Secondary
Change From Baseline in Hematocrit at Week 24
Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hematocrit at Week 24 | Week 24, n=822,769 | 0.0024 Fraction of 1 | Standard Deviation 0.02627 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hematocrit at Week 24 | Maximum post BL, n=880,857 | 0.0115 Fraction of 1 | Standard Deviation 0.02533 |
| BUD/FOR 400/12 µg | Change From Baseline in Hematocrit at Week 24 | Week 24, n=822,769 | 0.0024 Fraction of 1 | Standard Deviation 0.02798 |
| BUD/FOR 400/12 µg | Change From Baseline in Hematocrit at Week 24 | Maximum post BL, n=880,857 | 0.0123 Fraction of 1 | Standard Deviation 0.02669 |
Secondary
Change From Baseline in Hematocrit at Week 52
Blood samples were collected for the measurement of hematocrit (proportion of red blood cells in blood) at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as Most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hematocrit at Week 52 | Maximum post BL, n=206,212 | 0.0153 Fraction of 1 | Standard Deviation 0.02552 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hematocrit at Week 52 | Week 52, n=174,170 | -0.0056 Fraction of 1 | Standard Deviation 0.02468 |
| BUD/FOR 400/12 µg | Change From Baseline in Hematocrit at Week 52 | Week 52, n=174,170 | -0.0056 Fraction of 1 | Standard Deviation 0.0317 |
| BUD/FOR 400/12 µg | Change From Baseline in Hematocrit at Week 52 | Maximum post BL, n=206,212 | 0.0149 Fraction of 1 | Standard Deviation 0.02793 |
Secondary
Change From Baseline in Hemoglobin at Week 24
Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, and Week 24. Change from Baseline was calculated as the post-Baseline value at Week 24 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 24
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hemoglobin at Week 24 | Week 24, n=822,769 | -0.9 Grams per liter (g/L) | Standard Deviation 8.17 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hemoglobin at Week 24 | Maximum post BL, n=880,857 | 1.5 Grams per liter (g/L) | Standard Deviation 7.55 |
| BUD/FOR 400/12 µg | Change From Baseline in Hemoglobin at Week 24 | Week 24, n=822,769 | -1.0 Grams per liter (g/L) | Standard Deviation 8.65 |
| BUD/FOR 400/12 µg | Change From Baseline in Hemoglobin at Week 24 | Maximum post BL, n=880,857 | 1.5 Grams per liter (g/L) | Standard Deviation 8.26 |
Secondary
Change From Baseline in Hemoglobin at Week 52
Blood samples were collected for the measurement of hemoglobin at Baseline, Week 12, Week 24, and Week 52 for the extension part of the study. Change from Baseline was calculated as the post-Baseline value at Week 52 minus the Baseline value. Baseline was defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title). The maximum post-Baseline values have also been presented.
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hemoglobin at Week 52 | Week 52, n=174,170 | -2.5 g/L | Standard Deviation 8.06 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Hemoglobin at Week 52 | Maximum post BL, n=206,212 | 2.2 g/L | Standard Deviation 7.67 |
| BUD/FOR 400/12 µg | Change From Baseline in Hemoglobin at Week 52 | Week 52, n=174,170 | -2.5 g/L | Standard Deviation 9.82 |
| BUD/FOR 400/12 µg | Change From Baseline in Hemoglobin at Week 52 | Maximum post BL, n=206,212 | 1.9 g/L | Standard Deviation 8.55 |
Secondary
Change From Baseline in Pulse Rate at Week 24
Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat).
Time frame: Baseline and Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Pulse Rate at Week 24 | -0.5 Bpm | Standard Error 0.31 |
| BUD/FOR 400/12 µg | Change From Baseline in Pulse Rate at Week 24 | -0.8 Bpm | Standard Error 0.32 |
p-value: 0.52695% CI: [-0.6, 1.2]Mixed Model Repeated Measures
Secondary
Change From Baseline in Pulse Rate at Week 52
Pulse rate was obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation. Pulse rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline values for pulse rate at Week 52 were summarized and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization (generally Screening but could be a test repeat).
Time frame: Baseline and Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Pulse Rate at Week 52 | 0.7 Bpm | Standard Error 0.67 |
| BUD/FOR 400/12 µg | Change From Baseline in Pulse Rate at Week 52 | -1.9 Bpm | Standard Error 0.69 |
p-value: 0.00795% CI: [0.7, 4.5]Mixed Model Repeated Measures
Secondary
Change From Baseline in QTcB at Week 52
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24, and Week 52 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 52. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading.
Time frame: Baseline and Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in QTcB at Week 52 | 0.9 Msec | Standard Deviation 21.3 |
| BUD/FOR 400/12 µg | Change From Baseline in QTcB at Week 52 | 2.2 Msec | Standard Deviation 22.46 |
Secondary
Change From Baseline in QTcF and PR Interval at Week 52
Single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4, Week 24 and Week 52 or IP Discontinuation Visit. Change from Baseline in ECG QTcF and PR interval was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 52 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). Only participants with data available at the analysis time point were analyzed (represented as n=X, X in category title).
Time frame: Baseline and Week 52
Population: Extension Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in QTcF and PR Interval at Week 52 | QTcF, n=181,169 | 1.4 Msec | Standard Error 1.27 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in QTcF and PR Interval at Week 52 | PR, n=174,160 | 1.6 Msec | Standard Error 1.09 |
| BUD/FOR 400/12 µg | Change From Baseline in QTcF and PR Interval at Week 52 | QTcF, n=181,169 | 2.4 Msec | Standard Error 1.31 |
| BUD/FOR 400/12 µg | Change From Baseline in QTcF and PR Interval at Week 52 | PR, n=174,160 | 1.4 Msec | Standard Error 1.13 |
p-value: 0.56495% CI: [-4.7, 2.5]Mixed Model Repeated Measures
p-value: 0.90895% CI: [-2.9, 3.3]Mixed Model Repeated Measures
Secondary
Change From Baseline in QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Week 24
A single 12-lead ECG and rhythm strip were recorded after measurement of vital signs and spirometry. Recordings were made at Screening (Visit 1) and approximately 15-45 minutes after dosing on treatment Week 4 and Week 24 or IP Discontinuation Visit. Change from Baseline in QTcB was summarized for each post-Baseline assessment up to Week 24. Change from Baseline was calculated as the individual post-Baseline value at Week 24 minus the Baseline value. Baseline value is defined as the most recent individual value prior to randomization (generally Screening but could be a test repeat). All ECG measurements were made with the participants in a supine position having rested in this position for approximately 5 minutes before each reading.
Time frame: Baseline and Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Week 24 | 1.5 Msec | Standard Deviation 21 |
| BUD/FOR 400/12 µg | Change From Baseline in QT Interval Corrected for Heart Rate According to Bazett's Formula (QTcB) at Week 24 | -0.7 Msec | Standard Deviation 20.48 |
Secondary
Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 24
Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4 and Week 24 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were collected taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 24 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat).
Time frame: Baseline and Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 24 | SBP | -1.0 Millimeter of mercury (mmHg) | Standard Error 0.39 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 24 | DBP | -0.3 Millimeter of mercury (mmHg) | Standard Error 0.27 |
| BUD/FOR 400/12 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 24 | SBP | -1.1 Millimeter of mercury (mmHg) | Standard Error 0.4 |
| BUD/FOR 400/12 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 24 | DBP | -0.5 Millimeter of mercury (mmHg) | Standard Error 0.27 |
p-value: 0.84995% CI: [-1, 1.2]Mixed Model Repeated Measures
p-value: 0.61395% CI: [-0.6, 0.9]Mixed Model Repeated Measures
Secondary
Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 52
Vital signs were obtained at the Screening Visit and prior to taking the morning dose of study treatment and prior to conducting spirometry at Week 4, Week 24, and Week 52 or at the Study Treatment Discontinuation Visit. A single set of blood pressure (systolic and diastolic) measurements were taken after the participant had rested for 5 minutes in the sitting position. Change from Baseline values for systolic and diastolic BP (SBP and DBP) at Week 52 were summarised and these data were analyzed using MMRM analysis. Baseline was defined as the values from most recent assessment prior to randomization which records both systolic and diastolic BP (generally Screening but could be a test repeat).
Time frame: Baseline and Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 52 | SBP | -1.3 mmHg | Standard Error 0.83 |
| FF/UMEC/VI 100/62.5/25 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 52 | DBP | -0.4 mmHg | Standard Error 0.52 |
| BUD/FOR 400/12 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 52 | DBP | 0.4 mmHg | Standard Error 0.53 |
| BUD/FOR 400/12 µg | Change From Baseline in Systolic and Diastolic Blood Pressures (BP) at Week 52 | SBP | 0.3 mmHg | Standard Error 0.85 |
p-value: 0.18395% CI: [-3.9, 0.8]Mixed Model Repeated Measures
p-value: 0.25395% CI: [-2.3, 0.6]Mixed Model Repeated Measures
Secondary
Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 24
Participants were asked to complete the daily activity question as part of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline.
Time frame: Up to Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 24 | 0.0 Percentage of days | Standard Error 0.38 |
| BUD/FOR 400/12 µg | Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 24 | -0.1 Percentage of days | Standard Error 0.39 |
p-value: 0.81795% CI: [-0.9, 1.1]ANCOVA
Secondary
Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 52
Participants were asked to complete the daily activity question as aprt of the eDiary, which included the following options: 0: fewer activities, 1: no affect on my activities, and 2: more activities than usual. Daily activity question percentage of days with score of 2 over Weeks 1-24 was analysed using an ANCOVA model with covariates of treatment group, smoking status (screening), geographical region and baseline.
Time frame: Up to Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 52 | 0.0 Percentage of days | Standard Error 0.7 |
| BUD/FOR 400/12 µg | Daily Activity Question Percentage of Days Reporting a Score of 2 up to Week 52 | 0.3 Percentage of days | Standard Error 0.69 |
p-value: 0.76795% CI: [-2.1, 1.6]ANCOVA
Secondary
Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 24
The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant \[par.\] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence \[color\]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, \>=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1).
Time frame: Up to Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 24 | 0.22 Exacerbations per participant per year |
| BUD/FOR 400/12 µg | Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 24 | 0.34 Exacerbations per participant per year |
p-value: 0.00295% CI: [0.49, 0.86]Generalized linear modeL
Secondary
Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 52
The mean annual moderate and severe COPD exacerbations during the treatment (trt) period (per participant \[par.\] per year) was assessed. The event rate for exacerbations was calculated as the number of events x 1000 divided by the total participant exposure during the time-period of interest. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence \[color\]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. Analysis performed using a generalised linear model assuming a negative binomial distribution and covariates of treatment group, exacerbation history (0, 1, \>=2 moderate/severe), smoking status (screening), geographical region and post-bronchodilator percent predicted FEV1 (day 1).
Time frame: Up to Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 52 | 0.20 Exacerbations per participant per year |
| BUD/FOR 400/12 µg | Mean Annual On-treatment Moderate and/or Severe COPD Exacerbations up to Week 52 | 0.36 Exacerbations per participant per year |
p-value: 0.00695% CI: [0.37, 0.85]Generalized Linear model
Secondary
Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period
Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, Candida infection, oral fungal infection, and oropharyngeal candidiasis were reported.
Time frame: Up to Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Oral candidiasis | 2 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Candida infection | 1 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Oral fungal infection | 2 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Oropharyngeal candidiasis | 2 Participants |
| BUD/FOR 400/12 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Oropharyngeal candidiasis | 0 Participants |
| BUD/FOR 400/12 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Oral candidiasis | 4 Participants |
| BUD/FOR 400/12 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Oral fungal infection | 3 Participants |
| BUD/FOR 400/12 µg | Number of Participants Reporting an Adverse Event of Special Interest (AESI) of Oropharyngeal Origin in the Treatment Period | Candida infection | 4 Participants |
Secondary
Number of Participants Reporting an AESI of Oropharyngeal Origin in the Extension Part of the Study
Oropharyngeal examinations for clinical evidence of infection (e.g., Candida albicans) were performed at each clinic visit. All suspected cases of candidiasis were reported as AEs. The number of participants with oral candidiasis, candida infection, oral fungal infection, and oropharyngeal candidiasis were reported.
Time frame: Up to Week 52
Population: Extension Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants Reporting an AESI of Oropharyngeal Origin in the Extension Part of the Study | Oral fungal infection | 0 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants Reporting an AESI of Oropharyngeal Origin in the Extension Part of the Study | Candida infection | 0 Participants |
| BUD/FOR 400/12 µg | Number of Participants Reporting an AESI of Oropharyngeal Origin in the Extension Part of the Study | Oral fungal infection | 2 Participants |
| BUD/FOR 400/12 µg | Number of Participants Reporting an AESI of Oropharyngeal Origin in the Extension Part of the Study | Candida infection | 3 Participants |
Secondary
Number of Participants With an On-treatment Penumonia Event in the Extension Part of the Study
All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray AND at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature \> 37.5 °C), Elevated WBC (\>10,000/mm3 or \>15 percent immature forms) orr Hypoxemia (HbO2 saturation \<88 percent or at least 2 percent lower than Baseline value).
Time frame: Up to Week 52
Population: Extension Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With an On-treatment Penumonia Event in the Extension Part of the Study | 4 Participants |
| BUD/FOR 400/12 µg | Number of Participants With an On-treatment Penumonia Event in the Extension Part of the Study | 4 Participants |
Secondary
Number of Participants With an On-treatment Penumonia Event in the Treatment Period
All suspected pneumonias required confirmation as defined by the presence of new infiltrate(s) on chest x-ray and at least 2 of the following signs and symptoms: Increased cough, Increased sputum purulence (colour) or production, Auscultatory findings of adventitious sounds , Dyspnea or tachypnea, Fever (oral temperature \> 37.5 °C), Elevated white blood cells (WBC) (\>10,000/millimeter \[mm\^3\] or \>15 percent immature forms) or Hypoxemia (hemoglobin/oxygen \[HbO2\] saturation \<88 percent or at least 2 percent lower than Baseline value).
Time frame: Up to Week 24
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With an On-treatment Penumonia Event in the Treatment Period | 20 Participants |
| BUD/FOR 400/12 µg | Number of Participants With an On-treatment Penumonia Event in the Treatment Period | 7 Participants |
Secondary
Number of Participants With Any Abnormal Holter Electrocardiogram (ECG) Finding at Week 24
The 24-hour holter measurements were obtained at Screening and 24 hours prior to Week 24 (Visits 1 and 6). The number of participants with clinically significant change (abnormal) were reported. Holter Monitoring Population: all participants in the ITT Population who had at least one holter monitoring evaluation.
Time frame: Up to Week 24
Population: Holter Monitoring Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any Abnormal Holter Electrocardiogram (ECG) Finding at Week 24 | 180 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any Abnormal Holter Electrocardiogram (ECG) Finding at Week 24 | 165 Participants |
Secondary
Number of Participants With Any On-treatment Adverse Event (AE) and Serious Adverse Event (SAE) in the Treatment Period
An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint.
Time frame: Up to Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment Adverse Event (AE) and Serious Adverse Event (SAE) in the Treatment Period | Any AE | 354 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment Adverse Event (AE) and Serious Adverse Event (SAE) in the Treatment Period | Any SAE | 49 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment Adverse Event (AE) and Serious Adverse Event (SAE) in the Treatment Period | Any AE | 339 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment Adverse Event (AE) and Serious Adverse Event (SAE) in the Treatment Period | Any SAE | 51 Participants |
Secondary
Number of Participants With Any On-treatment AE/SAEs in the Extension Part of the Study
An AE was any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. These included an exacerbation of a chronic or intermittent pre-existing condition. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; or all events of possible drug-induced liver injury. Abnormal and clinically significant laboratory test results were also recorded as an AE or SAE. COPD exacerbations were an expected disease-related outcome and were not to be recorded as an AE, unless they met the definition of an SAE. Participants were not to be withdrawn from the study due to COPD exacerbations and their evaluation was an efficacy endpoint.
Time frame: Up to Week 52
Population: Extension Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment AE/SAEs in the Extension Part of the Study | Any AE | 100 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment AE/SAEs in the Extension Part of the Study | Any SAE | 21 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment AE/SAEs in the Extension Part of the Study | Any AE | 122 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment AE/SAEs in the Extension Part of the Study | Any SAE | 28 Participants |
Secondary
Number of Participants With Any On-treatment Cardiovascular (CV) Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Treatment Period
Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query \[SMQ; myocardial infarction SMQ and other ischemic diseases\]) and narrow MACE criteria (myocardial infarction \[acute myocardial infarction\].
Time frame: Up to Week 24
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment Cardiovascular (CV) Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Treatment Period | Any MACE, Narrow definition | 4 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment Cardiovascular (CV) Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Treatment Period | Any MACE, Broad definition | 12 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment Cardiovascular (CV) Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Treatment Period | Any MACE, Narrow definition | 7 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment Cardiovascular (CV) Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Treatment Period | Any MACE, Broad definition | 11 Participants |
Secondary
Number of Participants With Any On-treatment CV Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Extension Part of the Study
Cardiovascular safety was monitored via AE reporting with categorization and analysis of adverse events of special interest (AESIs) including cardiac arrhythmia, cardiac failure, ischemic heart disease, hypertension, and central nervous system hemorrhages and cerebrovascular conditions. In addition, ECGs and vital signs were measured in all subjects and24-hour Holter monitoring was performed in a predefined subset. Pre-specified MACE analysis was conducted based on adjudicated CV deaths and investigator-reported non-fatal AEs. Number of participants with any of the following MACE events were to be included per the broad and narrow analyses: Broad MACE criteria (ischemic heart disease standardized MedDRA query \[SMQ; myocardial infarction SMQ and other ischemic diseases\]) and narrow MACE criteria (myocardial infarction \[acute myocardial infarction\]
Time frame: Up to Week 52
Population: Extension Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment CV Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Extension Part of the Study | Any MACE, Narrow definition | 5 Participants |
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With Any On-treatment CV Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Extension Part of the Study | Any MACE, Broad definition | 7 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment CV Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Extension Part of the Study | Any MACE, Narrow definition | 2 Participants |
| BUD/FOR 400/12 µg | Number of Participants With Any On-treatment CV Events (Including Supraventricular Arrhythmia and Non Fatal Myocardial Infarction) in the Extension Part of the Study | Any MACE, Broad definition | 5 Participants |
Secondary
Number of Participants With at Least One On-treatment Bone Fracture Incident in the Extension Part of the Study
To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest.
Time frame: Up to Week 52
Population: Extension Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With at Least One On-treatment Bone Fracture Incident in the Extension Part of the Study | 0 Participants |
| BUD/FOR 400/12 µg | Number of Participants With at Least One On-treatment Bone Fracture Incident in the Extension Part of the Study | 1 Participants |
Secondary
Number of Participants With at Least One On-treatment Bone Fracture Incident in the Treatment Period
To evaluate the potential for bone systemic corticosteroid effects, the incidence of bone fractures was assessed. It was categorized as an adverse event of special interest.
Time frame: Up to Week 24
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Number of Participants With at Least One On-treatment Bone Fracture Incident in the Treatment Period | 4 Participants |
| BUD/FOR 400/12 µg | Number of Participants With at Least One On-treatment Bone Fracture Incident in the Treatment Period | 6 Participants |
Secondary
Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 24
The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Week 4 and Week 24. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions.
Time frame: Week 24
Population: ITT Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 24 | 2.29 Scores on a scale | Standard Error 0.096 |
| BUD/FOR 400/12 µg | Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 24 | 1.72 Scores on a scale | Standard Error 0.099 |
p-value: <0.00195% CI: [0.3, 0.84]Mixed effect repeated measures model
Secondary
Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 52
The TDI measures change in the participant's dyspnoea from Baseline. The scores in both indexes depend on ratings for three different categories: functional impairment; magnitude of task; and magnitude of effort. Each of these scales had a possible score ranging from -6 (major deterioration) to +6 (major improvement). TDI focal score was calculated as the sum of the three individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). TDI was measured at Weeks 4, 24 and 52. Analysis performed using a repeated measures model with covariates of treatment group, smoking status (screening), geographical region, visit, BDI focal score, BDI focal score by visit and treatment by visit interactions
Time frame: Week 52
Population: Extension Population; Only participants with analyzable data at the given time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FF/UMEC/VI 100/62.5/25 µg | Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 52 | 1.74 Scores on a scale | Standard Error 0.221 |
| BUD/FOR 400/12 µg | Transitional Dyspnea Index (TDI) Focal Score Expressed as Least Square Mean at Week 52 | 1.39 Scores on a scale | Standard Error 0.226 |
p-value: 0.27995% CI: [-0.28, 0.97]Mixed effect repeated measures model