Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
HRQoL, Disease Progression, Danirixin, COPD
Brief summary
This is a pilot study to investigate the effect of danirixin hydrobromide 35 milligram (mg) tablets on lung function and health related quality of life (HRQoL) in subjects with mild to moderate airflow obstruction and a demonstrated history of decline in forced expiratory volume in one second (FEV1). Specifically, this study aims to assess whether or not danirixin has the potential to impact disease progression in subjects with a COPD progression score indicating they are likely to decline based on 5 year data from a COPDGene study and support the conduct of a larger Phase III study for disease progression. Subjects will receive either placebo or danirixin 35 mg tablets (as hydrobromide hemihydrate salt) twice daily for 52 weeks (12months). Study subjects will continue with their standard of care inhaled medications (i.e. long acting bronchodilators with or without inhaled corticosteroids) while receiving study treatment. This study will be an ancillary study within the COPDGene study investigating the enrichment strategy for assessing disease progression. Potential subjects most likely to decline from the well established COPDGene cohort, will be based on data collected over the initial 5 year period. With the use of an enriched population, it is anticipated that one year of treatment will be sufficient to detect a trend in altering disease progression. Approximately 130 subjects will be screened to enroll 100 subjects in this study. The data from this study will provide useful information in determining whether to progress to a Phase III study to explore an indication for slowing disease progression.
Interventions
DRUGDanirixin 35 mg tablets
Danirixin 35 mg (as hydrobromide hemihydrate salt) is a white film coated oval shaped tablet. It will be provided in a labeled high-density polyethylene (HDPE) bottle with desiccant.
DRUGPlacebo
Placebo is a white film coated oval shaped tablet. It will be provided in a labeled HDPE bottle with desiccant.
DEVICEMetered dose inhaler (MDI) sensor device
MDI sensor devices will be fitted onto rescue medication MDI devices to electronically record rescue medication usage.
DRUGRescue medication
Subjects may continue to use rescue medication(s) via their usual route. Allowed medications are: short acting beta agonists (SABA) (e.g., albuterol/salbutamol); short acting muscarinic antagonists (SAMA) (e.g., ipratropium); short acting combination (SABA/SAMA) bronchodilators, (e.g. Duoneb, Combivent)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 76 Years
Healthy volunteers
No
Inclusion criteria
* Subject must be 40 to 76 years of age inclusive, at the time of signing the informed consent. * At the screening visit, the subject must have an FEV1 \>40 percent of the predicted normal. * Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD. * Body weight \>=45 kilogram (kg). * A male subject must agree to use contraception during the treatment period and for at least 60 hours after the last dose of study treatment, corresponding to approximately 6 half-lives (which is the time needed to eliminate any teratogenic study treatment) and to refrain from donating sperm during this period. * A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP). * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions for this study.
Exclusion criteria
* Diagnosis of other clinically relevant lung disease (other than COPD), e.g. sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung cancer. * COPD due to alpha-1-antitrypsin deficiency. * Pulse oximetry \<88 percent at rest at screening. Subjects should be tested while breathing room air. However, subjects living at high altitudes (above 5000 feet or 1500 meters above sea level) who are receiving supplemental oxygen can be included provided they are receiving the equivalent of \< 4Liter/minute and screening oximetry is measured while on their usual settings. * Less than 14 days have elapsed from completion of a course of antibiotics or oral corticosteroids for a recent COPD exacerbation. * Subjects with a peripheral blood neutrophil count \<1 x 10\^9/Liter. * Diagnosis of pneumonia (chest X-ray or computerized tomography \[CT\] confirmed) within the 3 months prior to screening. * Chest X-ray (posterior with lateral) or CT scan reveals evidence of a clinically significant abnormality not believed to be due to the presence of COPD (historic data up to 1 year may be used). * History or current evidence of clinically significant renal disease, diabetes mellitus/metabolic syndrome, hypertension, or any other clinically significant cardiovascular, neurological, immunological, endocrine, or hematological abnormality that is uncontrolled on permitted therapies. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subjects at risk through study participation, or which would affect the safety analysis or other analysis if the disease/condition exacerbated during the study. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator of GlaxoSmithKline (GSK) medical monitor, contraindicates their participation. * Current of chronic history of liver disease, or know hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Abnormal and clinically significant 12-lead ECG finding. The investigator 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 heat block Mobitz type II and third degree heart block (unless pacemaker or defibrillator has been implanted, or; QT interval corrected for heart rate per Friderica formula (QTcF) \>=500 milliseconds (msec) in subjects with QRS \<120 msec and QTcF \>=530 msec in subjects with QRS \>=120 msec. * Previous lung surgery (e.g. lobectomy, pneumonectomy) or lung volume reduction procedure. * Current or expected chronic use of macrolide antibiotics during the study period for the prevention of COPD exacerbations. Examples of chronic use include, but are not limited to, daily or two to three times per week use for at least 3 months. * Oral or injectable cytochrome P450 3A4 (CYP3A4) or breast cancer resistance protein (BRCP) substrates with a narrow therapeutic index (CYP3A4 substrates include, but are not limited to, alfenatil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, and theophylline; BCRP substrates include, but are not limited to, topotecan) The Investigator should consult with the medical monitor if necessary. * Current or expected use of phosphodiesterase-4 inhibitors (e.g. roflumilast). Subjects currently receiving roflumilast may be included if they are able to discontinue use from 30 days prior to screening through the completion of the follow up visit. * Participation in a previous clinical trial and has received an investigational product within any of the following time periods prior to the first dosing day in the current study: 30 days, 5 half lives, or twice the duration of the biological effect of the investigational product (whichever is longer). * Participation in a previous clinical trial with danirixin within 1 year prior to the first dosing day in the current study. * Exposure to more than four investigational products within 1 year prior to the first dosing day in the current study. * Alanine transferase (ALT) \>2 times upper limit of normal (ULN); bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent). * A positive test for human immunodeficiency virus (HIV) antibody. * A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody result within 3 months prior to screening. * Subjects who have taken part 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. * A history of allergy or hypersensitivity to any of the ingredients in the study treatment. * A known or suspected history of alcohol or drug abuse within the 2 years prior to screening. * In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete study related materials. * Study investigators, sub-investigators, study coordinators, employees of a study investigator, sub-investigator or study site, or immediate family member of any of the above that are involved with the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Decline in Forced Expiratory Volume in One Second (FEV1) | Up 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. The effect of treatment on decline of post bronchodilator FEV1 recorded during the treatment period was analyzed using a repeated measures random coefficients model with covariates of treatment group, age, sex, smoking status, baseline FEV1, body mass index (BMI), study day and the treatment group by study day interaction. The adjusted mean and standard error for rate of decline in FEV1 have been presented. |
| Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C]) | Baseline (Day 1 pre-dose), Weeks 12, 24 and 32 | 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 according to manual. The SGRQ Questionnaire is a well-established, self-completed tool, with 50 questions comprising three domains; Symptoms, Activity, and Impacts scores (each ranging from 0 to 100). SGRQ total score was calculated by summing weights from all positive items, divided by sum of weights for all items in SGRQ questionnaire and multiplying by 100. The SGRQ total score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post dose visit value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Up to Week 52 | Blood samples for clinical chemistry parameters were collected at indicated time points. PCI ranges were, calcium (millimoles per liter \[mmol/L\]): 0.85x (low) or 1.08x (high), bicarbonate (mmol/L): \<18 (low) or \>32 (high), chloride (mmol/L): 0.90x (low) or 1.10x (high), creatinine (micromoles per liter\[µmol/L\]): 1.30x (high), glucose(mmol/L): \<0.6x (low) or \>4x (high), potassium (mmol/L): 0.75x (low) or 1.30x (high), sodium (mmol/L): 0.80x (low) or 1.15x (high), total protein (milligram per deciliter\[mg/dL\]): 1.25x (high), blood urea nitrogen(BUN) (mmol/L): 0.70x (low) or 1.60x(high). Participants were counted in the worst case if their laboratory value changes to low, or within range or no change, or high. Participants were counted in within range if their value was unchanged. Limits with 'x' are multipliers of central laboratory normal range. |
| Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Up to Week 52 | Blood samples for liver function tests were collected at indicated time points. PCI ranges were, alanine aminotransferase (ALT) (units per liter\[U/L\]): \>=3x upper limit of normal (ULN) (high), alkaline phosphatase (alk phosp) (U/L): \>=2x ULN (high), aspartate amino transferase (AST) (U/L): \>=3x ULN (high), direct bilirubin (µmol/L): \>=2x ULN (high), total bilirubin (µmol/L): \>=2x ULN (high). Participants were counted in the worst case if their laboratory value changes to low, or within range or no change, or high. Participants were counted in within range if their value was unchanged. Limits with 'x' are multipliers of central laboratory normal range. |
| Number of Participants With Abnormalities in Urinalysis Data | Up to Week 52 | Urine samples were planned to be collected to analyze the following parameters: specific gravity, pH, glucose, protein, blood and ketones. This analysis was planned but data was not collected, as study was terminated pre-maturely. |
| Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | Baseline (Day 1 pre-dose), Weeks 4, 12 and 24 | 12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained at pre-dose on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | Baseline (Day 1 pre-dose), Weeks 4, 12 and 24 | 12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained at pre-dose on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Up to Week 52 | Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate and respiratory rate. Vital signs were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury): \<90 (low) or \>160 (high), DBP (millimeters of mercury): \<40 (low) or \>110 (high), heart rate (beats per minute): \<35 (low) or \>120 (high), respiration rate (breaths per minute): \<8 (low) or \>30 (high). Participants were counted in the worst-case category that their value changes to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category were unchanged (high to high), or whose value became within range, were recorded in the 'to within range or no change' category. |
| C-reactive Protein (CRP) Levels (Safety Biomarker) After Administration of Danirixin | Up to Week 52 | Peripheral venous blood samples were planned to be collected and tested for biomarker that was indicative of inflammation (CRP). This analysis was planned but data was not collected, as the study was terminated pre-maturely. |
| Time to First Healthcare Resource Utilization (HCRU) Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Up to Week 52 | An exacerbation of COPD was defined by a worsening of symptoms requiring additional treatment or hospitalization. The date of onset of COPD exacerbations were planned to be recorded. This analysis was planned but data was not collected, as the study was terminated pre-maturely. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs) | Up to Week 52 | An AE is 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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention was categorized as SAE. Number of participants with AEs and SAEs are summarized. |
| Number of SGRQ Responders | Weeks 12, 24 and 32 | Response was defined as a SGRQ total score of 4 units below Baseline or lower. The SGRQ Questionnaire is a well-established, self-completed tool, with 50 questions comprising three domains; Symptoms, Activity, and Impacts scores (each ranging from 0 to 100). SGRQ total score was calculated by summing weights from all positive items, divided by sum of weights for all items in SGRQ questionnaire and multiplying by 100. The SGRQ total score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Number of SGRQ responders are presented. |
| Change From Baseline in SGRQ Symptoms Score | Baseline (Day 1 pre-dose), Weeks 12, 24 and 32 | The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptoms score and Part 2 produces the activity and impacts score. SGRQ symptoms score was calculated by summing weights from all positive items in symptoms score component, divided by sum of weights for all items in symptoms score component and multiplying by 100. The SGRQ symptoms score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in SGRQ Activity Score | Baseline (Day 1 pre-dose), Weeks 12, 24 and 32 | The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure quality of life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptoms score and Part 2 produces the activity and impacts score. SGRQ activity score was calculated by summing weights from all positive items in activity score component, divided by sum of weights for all items in activity score component and multiplying by 100. The SGRQ activity score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in SGRQ Impacts Score | Baseline (Day 1 pre-dose), Weeks 12, 24 and 32 | The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptoms score and Part 2 produces the activity and impacts score. SGRQ impacts score was calculated by summing weights from all positive items in impacts score component, divided by sum of weights for all items in impacts score component and multiplying by 100. The SGRQ impacts score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in COPD Assessment Test (CAT) Score | Baseline (Day 1 pre-dose), Weeks 12, 24 and 32 | The COPD Assessment Test (CAT) is a short and simple participant completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (maximum impairment) to 5 (no impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated greater disease impact. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Baseline (Day 1 pre-dose), Weeks 1-4, Weeks 5-8, Weeks 9-12, Weeks 13-16, Weeks 17-20, Weeks 21-24, Weeks 25-28, Weeks 29-32, Weeks 33-36, Weeks 37-40, Weeks 41-44 and Weeks 45-48 | Participants were instructed to complete the daily diary in the evening to collect the number of puffs of rescue medications over each 24-hour period. The maximum number of puffs of rescue medications use were counted for the day and were used to determine if it was a recue-free day. A rescue-free day was defined as a day where the total number of puffs were 0. The 4-weekly means were calculated and presented. Baseline was defined as the mean number of puffs of rescue medication per day from the latest (7 days before study treatment start date and date of Screening) to the day before study treatment start date. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Baseline (Day 1 pre-dose), Weeks 1-4, Weeks 5-8, Weeks 9-12, Weeks 13-16, Weeks 17-20, Weeks 21-24, Weeks 25-28, Weeks 29-32, Weeks 33-36, Weeks 37-40, Weeks 41-44 and Weeks 45-48 | Participants were instructed to complete the daily diary in the evening to collect the number of puffs of rescue medications over each 24-hour period. The maximum number of puffs of rescue medication use were counted for the day and were used to determine if it was a recue-free day. A rescue-free day was defined as a day where the total number of puffs were 0. The 4-weekly means were calculated and presented. Baseline was defined as the mean number of puffs of rescue medication per day from the latest (7 days before study treatment start date and date of Screening) to the day before study treatment start date. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Change From Baseline in FEV1 | Baseline (Day 1 pre-dose), Weeks 2, 4, 8, 12, 16, 20, 24, 32 and 40 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were collected using a spirometer. Baseline was defined as the measurement performed prior to the first dose on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. |
| Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Up to Week 52 | Blood samples were collected. PCI ranges were, basophils(%):5x(high), eosinophils(%):2x(high), hematocrit(proportion of red blood cells in blood):0.50x(low) or 1.30x(high), hemoglobin (grams per liter):0.85x(low) or 1.20x(high), lymphocytes(%):0.80x(low) or 1.20x(high), mean corpuscle hemoglobin(picogram):0.85x(low) or 1.20x(high), mean corpuscle hemoglobin concentration(gram per deciliter):0.85x(low) or 1.10x(high), mean corpuscle volume(femtoliter):0.25x(low) or 2.00x(high), monocytes(%):0.80x(low) or 1.60x(high), platelet(x10\^9 cells per liter\[cells/L\]):0.90x(low) or 1.10x(high), Red Blood Cell(x10\^12 cells/L):0.93x(low) or 1.07x(high), neutrophil(%):0.65x(low) or 1.50x(high), White Blood Cell(x10\^9 cells/L):0.70x(low) or 1.60x(high). Participants were counted in the worst case if their laboratory value changes to low/within range or no change/high and were counted in the within range if their value was unchanged. Limits with 'x' are multipliers of central laboratory normal range. |
Countries
United States
Participant flow
Recruitment details
This study was originally designed for 52 weeks of treatment in participants with mild to moderate chronic obstructive pulmonary disease (COPD); however, the study was terminated early due to a change in the benefit-risk ratio of danirixin hydrogen bromide (DNX HBr).
Pre-assignment details
A total of 86 participants were screened, of them, 54 participants were randomized in a ratio of 1:1 to receive either placebo or 35 milligrams (mg) DNX HBr. Due to early termination of the study, no participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received one tablet of placebo with food twice daily for 52 weeks. | 27 |
| DNX HBr 35 mg Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks. | 27 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Study closed/terminated | 26 | 23 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | DNX HBr 35 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 66.1 Years STANDARD_DEVIATION 5.86 | 66.1 Years STANDARD_DEVIATION 6.33 | 66.0 Years STANDARD_DEVIATION 6.88 |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized White- White/Caucasian/European Heritage | 23 Participants | 45 Participants | 22 Participants |
| Sex: Female, Male Female | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Male | 19 Participants | 36 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 1 / 27 |
| other Total, other adverse events | 9 / 27 | 14 / 27 |
| serious Total, serious adverse events | 0 / 27 | 2 / 27 |
Outcome results
Primary
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C])
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 according to manual. The SGRQ Questionnaire is a well-established, self-completed tool, with 50 questions comprising three domains; Symptoms, Activity, and Impacts scores (each ranging from 0 to 100). SGRQ total score was calculated by summing weights from all positive items, divided by sum of weights for all items in SGRQ questionnaire and multiplying by 100. The SGRQ total score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32
Population: Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C]) | Week 12; n=17,18 | 0.23 Scores on a scale | Standard Deviation 6.963 |
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C]) | Week 24; n=10,7 | 2.12 Scores on a scale | Standard Deviation 5.498 |
| Placebo | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C]) | Week 32; n=5,3 | 1.96 Scores on a scale | Standard Deviation 12.215 |
| DNX HBr 35 mg | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C]) | Week 12; n=17,18 | 3.92 Scores on a scale | Standard Deviation 9.527 |
| DNX HBr 35 mg | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C]) | Week 24; n=10,7 | -0.41 Scores on a scale | Standard Deviation 7.673 |
| DNX HBr 35 mg | Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score (Derived From SGRQ-Chronic Obstructive Pulmonary Disease Specific Tool [SGRQ-C]) | Week 32; n=5,3 | 0.49 Scores on a scale | Standard Deviation 9.679 |
Primary
Rate of Decline in Forced Expiratory Volume in One Second (FEV1)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The effect of treatment on decline of post bronchodilator FEV1 recorded during the treatment period was analyzed using a repeated measures random coefficients model with covariates of treatment group, age, sex, smoking status, baseline FEV1, body mass index (BMI), study day and the treatment group by study day interaction. The adjusted mean and standard error for rate of decline in FEV1 have been presented.
Time frame: Up to Week 52
Population: Safety Population comprised all participants randomized to treatment, excluding those who were randomized in error. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rate of Decline in Forced Expiratory Volume in One Second (FEV1) | -132.8 Milliliters per year | Standard Error 110.75 |
| DNX HBr 35 mg | Rate of Decline in Forced Expiratory Volume in One Second (FEV1) | -200.0 Milliliters per year | Standard Error 115.01 |
p-value: 0.67995% CI: [-400.6, 266.2]Repeated measures random coefficient
Secondary
Change From Baseline in COPD Assessment Test (CAT) Score
The COPD Assessment Test (CAT) is a short and simple participant completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (maximum impairment) to 5 (no impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated greater disease impact. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in COPD Assessment Test (CAT) Score | Week 12;n=16,17 | -1.5 Scores on a scale | Standard Deviation 5.42 |
| Placebo | Change From Baseline in COPD Assessment Test (CAT) Score | Week 24;n=10,6 | -1.5 Scores on a scale | Standard Deviation 5.46 |
| Placebo | Change From Baseline in COPD Assessment Test (CAT) Score | Week 32;n=4,3 | 2.0 Scores on a scale | Standard Deviation 4.08 |
| DNX HBr 35 mg | Change From Baseline in COPD Assessment Test (CAT) Score | Week 12;n=16,17 | 2.6 Scores on a scale | Standard Deviation 5.68 |
| DNX HBr 35 mg | Change From Baseline in COPD Assessment Test (CAT) Score | Week 24;n=10,6 | 0.7 Scores on a scale | Standard Deviation 6.15 |
| DNX HBr 35 mg | Change From Baseline in COPD Assessment Test (CAT) Score | Week 32;n=4,3 | 5.3 Scores on a scale | Standard Deviation 3.51 |
Secondary
Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals
12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline was defined as the value obtained at pre-dose on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 4, 12 and 24
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | PR interval;Week 12;n=17,19 | 1.8 Milliseconds | Standard Deviation 12.4 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | Uncorrected QT interval;Week 4;n=25,25 | 0.9 Milliseconds | Standard Deviation 21.37 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QRS interval;Week 4;n=25,25 | -1.3 Milliseconds | Standard Deviation 4.9 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | Uncorrected QT interval;Week 12;n=17,19 | 3.7 Milliseconds | Standard Deviation 16.43 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | PR interval;Week 4;n=25,25 | 0.7 Milliseconds | Standard Deviation 8.88 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | Uncorrected QT interval;Week 24;n=10,8 | -0.5 Milliseconds | Standard Deviation 17 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QRS interval;Week 12;n=17,19 | -2.5 Milliseconds | Standard Deviation 6.47 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | PR interval;Week 24;n=9,8 | 2.2 Milliseconds | Standard Deviation 8.45 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QTc interval;Week 12;n=2,7 | -13.0 Milliseconds | Standard Deviation 18.38 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QRS interval;Week 24;n=10,8 | -2.9 Milliseconds | Standard Deviation 9.26 |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QTc interval;Week 24;n=1,3 | -7.0 Milliseconds | — |
| Placebo | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QTc interval;Week 4;n=3,8 | -1.9 Milliseconds | Standard Deviation 6.3 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QTc interval;Week 24;n=1,3 | 4.4 Milliseconds | Standard Deviation 9.05 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | PR interval;Week 4;n=25,25 | 0.4 Milliseconds | Standard Deviation 16.29 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | PR interval;Week 12;n=17,19 | -3.3 Milliseconds | Standard Deviation 15.83 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | PR interval;Week 24;n=9,8 | -3.2 Milliseconds | Standard Deviation 12.79 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QRS interval;Week 4;n=25,25 | 0.0 Milliseconds | Standard Deviation 5.4 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QRS interval;Week 12;n=17,19 | -3.0 Milliseconds | Standard Deviation 4.42 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QRS interval;Week 24;n=10,8 | 0.5 Milliseconds | Standard Deviation 5.11 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | Uncorrected QT interval;Week 4;n=25,25 | -3.7 Milliseconds | Standard Deviation 16.78 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | Uncorrected QT interval;Week 12;n=17,19 | -9.9 Milliseconds | Standard Deviation 45.86 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | Uncorrected QT interval;Week 24;n=10,8 | 8.2 Milliseconds | Standard Deviation 21.84 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QTc interval;Week 4;n=3,8 | 0.1 Milliseconds | Standard Deviation 13.96 |
| DNX HBr 35 mg | Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals | QTc interval;Week 12;n=2,7 | -21.4 Milliseconds | Standard Deviation 62.39 |
Secondary
Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate
12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the value obtained at pre-dose on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 4, 12 and 24
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | Week 4;n=25,25 | -0.7 Beats per minute | Standard Deviation 8.61 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | Week 12;n=17,19 | -2.8 Beats per minute | Standard Deviation 5.43 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | Week 24;n=10,8 | -0.7 Beats per minute | Standard Deviation 6.14 |
| DNX HBr 35 mg | Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | Week 4;n=25,25 | 0.5 Beats per minute | Standard Deviation 6.5 |
| DNX HBr 35 mg | Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | Week 12;n=17,19 | 1.5 Beats per minute | Standard Deviation 9.93 |
| DNX HBr 35 mg | Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate | Week 24;n=10,8 | 1.2 Beats per minute | Standard Deviation 7.85 |
Secondary
Change From Baseline in FEV1
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were collected using a spirometer. Baseline was defined as the measurement performed prior to the first dose on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 2, 4, 8, 12, 16, 20, 24, 32 and 40
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in FEV1 | Week 16;n=14,15 | -0.0515 Liters | Standard Deviation 0.16156 |
| Placebo | Change From Baseline in FEV1 | Week 8;n=18,20 | -0.0375 Liters | Standard Deviation 0.18245 |
| Placebo | Change From Baseline in FEV1 | Week 20;n=14,11 | -0.0197 Liters | Standard Deviation 0.19092 |
| Placebo | Change From Baseline in FEV1 | Week 4;n=25,25 | -0.0309 Liters | Standard Deviation 0.16173 |
| Placebo | Change From Baseline in FEV1 | Week 24;n=10,8 | 0.0030 Liters | Standard Deviation 0.19217 |
| Placebo | Change From Baseline in FEV1 | Week 12;n=18,19 | -0.0744 Liters | Standard Deviation 0.12213 |
| Placebo | Change From Baseline in FEV1 | Week 32;n=5,3 | -0.1964 Liters | Standard Deviation 0.11034 |
| Placebo | Change From Baseline in FEV1 | Week 40;n=3,1 | -0.2907 Liters | Standard Deviation 0.09209 |
| Placebo | Change From Baseline in FEV1 | Week 2;n=26,25 | 0.0383 Liters | Standard Deviation 0.23206 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 40;n=3,1 | -0.2010 Liters | — |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 2;n=26,25 | -0.0152 Liters | Standard Deviation 0.11936 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 4;n=25,25 | 0.0038 Liters | Standard Deviation 0.15194 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 8;n=18,20 | -0.0251 Liters | Standard Deviation 0.19673 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 12;n=18,19 | -0.0014 Liters | Standard Deviation 0.20688 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 16;n=14,15 | -0.0480 Liters | Standard Deviation 0.23974 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 20;n=14,11 | -0.0939 Liters | Standard Deviation 0.11837 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 24;n=10,8 | -0.1301 Liters | Standard Deviation 0.16956 |
| DNX HBr 35 mg | Change From Baseline in FEV1 | Week 32;n=5,3 | -0.1340 Liters | Standard Deviation 0.32707 |
Secondary
Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals
Participants were instructed to complete the daily diary in the evening to collect the number of puffs of rescue medications over each 24-hour period. The maximum number of puffs of rescue medication use were counted for the day and were used to determine if it was a recue-free day. A rescue-free day was defined as a day where the total number of puffs were 0. The 4-weekly means were calculated and presented. Baseline was defined as the mean number of puffs of rescue medication per day from the latest (7 days before study treatment start date and date of Screening) to the day before study treatment start date. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 1-4, Weeks 5-8, Weeks 9-12, Weeks 13-16, Weeks 17-20, Weeks 21-24, Weeks 25-28, Weeks 29-32, Weeks 33-36, Weeks 37-40, Weeks 41-44 and Weeks 45-48
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 1-4;n=23,25 | -0.16 Number of puffs per day | Standard Deviation 3.217 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 5-8;n=20,20 | -0.11 Number of puffs per day | Standard Deviation 3.754 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 9-12;n=16,19 | -0.61 Number of puffs per day | Standard Deviation 3.909 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 13-16;n=15,16 | -1.15 Number of puffs per day | Standard Deviation 6.458 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 17-20;n=13,12 | -1.33 Number of puffs per day | Standard Deviation 6.983 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 21-24;n=12,8 | -1.29 Number of puffs per day | Standard Deviation 7.317 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 25-28;n=9,7 | -2.56 Number of puffs per day | Standard Deviation 8.047 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 29-32;n=6,4 | 0.07 Number of puffs per day | Standard Deviation 0.161 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 33-36;n=5,3 | 0.30 Number of puffs per day | Standard Deviation 0.411 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 37-40;n=3,3 | 0.50 Number of puffs per day | Standard Deviation 0.866 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 41-44;n=3,1 | 0.27 Number of puffs per day | Standard Deviation 0.469 |
| Placebo | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 45-48;n=2,0 | 0.00 Number of puffs per day | Standard Deviation 0 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 1-4;n=23,25 | -0.11 Number of puffs per day | Standard Deviation 0.887 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 33-36;n=5,3 | -0.23 Number of puffs per day | Standard Deviation 1.724 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 5-8;n=20,20 | -0.30 Number of puffs per day | Standard Deviation 1.223 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 25-28;n=9,7 | 0.22 Number of puffs per day | Standard Deviation 1.26 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 9-12;n=16,19 | -0.34 Number of puffs per day | Standard Deviation 1.433 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 41-44;n=3,1 | 0.43 Number of puffs per day | — |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 13-16;n=15,16 | -0.36 Number of puffs per day | Standard Deviation 1.785 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 29-32;n=6,4 | -0.33 Number of puffs per day | Standard Deviation 1.201 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 17-20;n=13,12 | 0.08 Number of puffs per day | Standard Deviation 1.738 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 37-40;n=3,3 | -0.06 Number of puffs per day | Standard Deviation 1.959 |
| DNX HBr 35 mg | Change From Baseline in Mean Number of Puffs Per Day of Rescue Medication Using Diary Data in 4-week Intervals | Weeks 21-24;n=12,8 | 0.24 Number of puffs per day | Standard Deviation 1.149 |
Secondary
Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals
Participants were instructed to complete the daily diary in the evening to collect the number of puffs of rescue medications over each 24-hour period. The maximum number of puffs of rescue medications use were counted for the day and were used to determine if it was a recue-free day. A rescue-free day was defined as a day where the total number of puffs were 0. The 4-weekly means were calculated and presented. Baseline was defined as the mean number of puffs of rescue medication per day from the latest (7 days before study treatment start date and date of Screening) to the day before study treatment start date. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 1-4, Weeks 5-8, Weeks 9-12, Weeks 13-16, Weeks 17-20, Weeks 21-24, Weeks 25-28, Weeks 29-32, Weeks 33-36, Weeks 37-40, Weeks 41-44 and Weeks 45-48
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 1-4;n=23,25 | -11.3 Percentage of days | Standard Deviation 28.79 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 5-8;n=20,20 | -15.3 Percentage of days | Standard Deviation 32.83 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 9-12;n=16,19 | -6.4 Percentage of days | Standard Deviation 30.27 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 13-16;n=15,16 | -13.8 Percentage of days | Standard Deviation 34.82 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 17-20;n=13,12 | -6.5 Percentage of days | Standard Deviation 24.61 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 21-24;n=12,8 | -11.0 Percentage of days | Standard Deviation 25.38 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 25-28;n=9,7 | -2.0 Percentage of days | Standard Deviation 11.33 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 29-32;n=6,4 | 1.7 Percentage of days | Standard Deviation 4.58 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 33-36;n=5,3 | -4.3 Percentage of days | Standard Deviation 7.86 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 37-40;n=3,3 | -1.2 Percentage of days | Standard Deviation 2.06 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 41-44;n=3,1 | 0.5 Percentage of days | Standard Deviation 0.87 |
| Placebo | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 45-48;n=2,0 | 0.0 Percentage of days | Standard Deviation 0 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 1-4;n=23,25 | 1.9 Percentage of days | Standard Deviation 20.42 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 33-36;n=5,3 | 3.0 Percentage of days | Standard Deviation 72.22 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 5-8;n=20,20 | 3.0 Percentage of days | Standard Deviation 25.88 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 25-28;n=9,7 | -4.9 Percentage of days | Standard Deviation 40.02 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 9-12;n=16,19 | 3.3 Percentage of days | Standard Deviation 26.54 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 41-44;n=3,1 | -21.4 Percentage of days | — |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 13-16;n=15,16 | 2.0 Percentage of days | Standard Deviation 30.49 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 29-32;n=6,4 | 10.0 Percentage of days | Standard Deviation 46.71 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 17-20;n=13,12 | 2.3 Percentage of days | Standard Deviation 35 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 37-40;n=3,3 | -0.5 Percentage of days | Standard Deviation 77.88 |
| DNX HBr 35 mg | Change From Baseline in Mean Percentage Rescue Free Days Using Diary Data in 4-week Intervals | Weeks 21-24;n=12,8 | -4.8 Percentage of days | Standard Deviation 38.88 |
Secondary
Change From Baseline in SGRQ Activity Score
The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure quality of life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptoms score and Part 2 produces the activity and impacts score. SGRQ activity score was calculated by summing weights from all positive items in activity score component, divided by sum of weights for all items in activity score component and multiplying by 100. The SGRQ activity score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Activity Score | Week 12;n=17,18 | -1.89 Scores on a scale | Standard Deviation 7.882 |
| Placebo | Change From Baseline in SGRQ Activity Score | Week 24;n=10,7 | 2.09 Scores on a scale | Standard Deviation 11.085 |
| Placebo | Change From Baseline in SGRQ Activity Score | Week 32;n=5,3 | 2.89 Scores on a scale | Standard Deviation 9.69 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Activity Score | Week 12;n=17,18 | 2.69 Scores on a scale | Standard Deviation 11.732 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Activity Score | Week 24;n=10,7 | -0.91 Scores on a scale | Standard Deviation 8.75 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Activity Score | Week 32;n=5,3 | -2.44 Scores on a scale | Standard Deviation 16.52 |
Secondary
Change From Baseline in SGRQ Impacts Score
The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptoms score and Part 2 produces the activity and impacts score. SGRQ impacts score was calculated by summing weights from all positive items in impacts score component, divided by sum of weights for all items in impacts score component and multiplying by 100. The SGRQ impacts score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Impacts Score | Week 12;n=17,18 | 2.36 Scores on a scale | Standard Deviation 9.801 |
| Placebo | Change From Baseline in SGRQ Impacts Score | Week 24;n=10,7 | 4.65 Scores on a scale | Standard Deviation 6.255 |
| Placebo | Change From Baseline in SGRQ Impacts Score | Week 32;n=5,3 | 1.45 Scores on a scale | Standard Deviation 11.983 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Impacts Score | Week 12;n=17,18 | 6.07 Scores on a scale | Standard Deviation 11.255 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Impacts Score | Week 24;n=10,7 | 2.01 Scores on a scale | Standard Deviation 8.003 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Impacts Score | Week 32;n=5,3 | 3.04 Scores on a scale | Standard Deviation 3.778 |
Secondary
Change From Baseline in SGRQ Symptoms Score
The SGRQ Questionnaire is a well-established, self-completed tool, comprising of 50 questions with 76 weighted responses designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts; Part 1 produces the symptoms score and Part 2 produces the activity and impacts score. SGRQ symptoms score was calculated by summing weights from all positive items in symptoms score component, divided by sum of weights for all items in symptoms score component and multiplying by 100. The SGRQ symptoms score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Baseline was defined as the score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Symptoms Score | Week 12;n=17,18 | -2.56 Scores on a scale | Standard Deviation 8.525 |
| Placebo | Change From Baseline in SGRQ Symptoms Score | Week 24;n=10,7 | -6.25 Scores on a scale | Standard Deviation 17.246 |
| Placebo | Change From Baseline in SGRQ Symptoms Score | Week 32;n=5,3 | 1.71 Scores on a scale | Standard Deviation 18.006 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Symptoms Score | Week 12;n=17,18 | -0.86 Scores on a scale | Standard Deviation 22.513 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Symptoms Score | Week 24;n=10,7 | -7.34 Scores on a scale | Standard Deviation 29.528 |
| DNX HBr 35 mg | Change From Baseline in SGRQ Symptoms Score | Week 32;n=5,3 | -2.07 Scores on a scale | Standard Deviation 36.896 |
Secondary
C-reactive Protein (CRP) Levels (Safety Biomarker) After Administration of Danirixin
Peripheral venous blood samples were planned to be collected and tested for biomarker that was indicative of inflammation (CRP). This analysis was planned but data was not collected, as the study was terminated pre-maturely.
Time frame: Up to Week 52
Population: Safety Population. This analysis was planned but data was not collected, as the sample size was too small and study was terminated pre-maturely.
Secondary
Number of Participants With Abnormalities in Urinalysis Data
Urine samples were planned to be collected to analyze the following parameters: specific gravity, pH, glucose, protein, blood and ketones. This analysis was planned but data was not collected, as study was terminated pre-maturely.
Time frame: Up to Week 52
Population: Safety Population. This analysis was planned but data was not collected, as study was terminated pre-maturely.
Secondary
Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs)
An AE is 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. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention was categorized as SAE. Number of participants with AEs and SAEs are summarized.
Time frame: Up to Week 52
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs) | AEs | 9 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs) | SAEs | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs) | AEs | 14 Participants |
| DNX HBr 35 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs) | SAEs | 2 Participants |
Secondary
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Blood samples for clinical chemistry parameters were collected at indicated time points. PCI ranges were, calcium (millimoles per liter \[mmol/L\]): 0.85x (low) or 1.08x (high), bicarbonate (mmol/L): \<18 (low) or \>32 (high), chloride (mmol/L): 0.90x (low) or 1.10x (high), creatinine (micromoles per liter\[µmol/L\]): 1.30x (high), glucose(mmol/L): \<0.6x (low) or \>4x (high), potassium (mmol/L): 0.75x (low) or 1.30x (high), sodium (mmol/L): 0.80x (low) or 1.15x (high), total protein (milligram per deciliter\[mg/dL\]): 1.25x (high), blood urea nitrogen(BUN) (mmol/L): 0.70x (low) or 1.60x(high). Participants were counted in the worst case if their laboratory value changes to low, or within range or no change, or high. Participants were counted in within range if their value was unchanged. Limits with 'x' are multipliers of central laboratory normal range.
Time frame: Up to Week 52
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Chloride, to within range or no change;n=25,25 | 25 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Glucose;to high;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Bicarbonate;to within range or no change;n=25,25 | 24 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Potassium;to low;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Chloride, to high;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Potassium;to within range or no change;n=25,25 | 25 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Calcium;to within range or no change;n=25,25 | 25 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Potassium;to high;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Creatinine;to low;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Sodium;to low;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Bicarbonate;to high;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Sodium;to within range or no change;n=25,25 | 25 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Creatinine;to within range or no change;n=25,25 | 24 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Sodium;to high;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Bicarbonate;to low;n=25,25 | 1 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Total protein;to low;n=26,26 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Creatinine;to high;n=25,25 | 1 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Total protein;to within range/no change;n=26,26 | 26 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Chloride, to low;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Total protein;to high;n=26,26 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Glucose;to low;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | BUN;to low;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Calcium;to high;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | BUN;to within range or no change;n=25,25 | 25 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Glucose;to within range or no change;n=25,25 | 25 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | BUN;to high;n=25,25 | 0 Participants |
| Placebo | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Calcium;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | BUN;to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Calcium;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Calcium;to within range or no change;n=25,25 | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Calcium;to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Bicarbonate;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Bicarbonate;to within range or no change;n=25,25 | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Bicarbonate;to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Chloride, to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Chloride, to within range or no change;n=25,25 | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Chloride, to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Creatinine;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Creatinine;to within range or no change;n=25,25 | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Creatinine;to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Glucose;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Glucose;to within range or no change;n=25,25 | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Glucose;to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Potassium;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Potassium;to within range or no change;n=25,25 | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Potassium;to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Sodium;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Sodium;to within range or no change;n=25,25 | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Sodium;to high;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Total protein;to low;n=26,26 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Total protein;to within range/no change;n=26,26 | 26 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | Total protein;to high;n=26,26 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | BUN;to low;n=25,25 | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria | BUN;to within range or no change;n=25,25 | 25 Participants |
Secondary
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Blood samples were collected. PCI ranges were, basophils(%):5x(high), eosinophils(%):2x(high), hematocrit(proportion of red blood cells in blood):0.50x(low) or 1.30x(high), hemoglobin (grams per liter):0.85x(low) or 1.20x(high), lymphocytes(%):0.80x(low) or 1.20x(high), mean corpuscle hemoglobin(picogram):0.85x(low) or 1.20x(high), mean corpuscle hemoglobin concentration(gram per deciliter):0.85x(low) or 1.10x(high), mean corpuscle volume(femtoliter):0.25x(low) or 2.00x(high), monocytes(%):0.80x(low) or 1.60x(high), platelet(x10\^9 cells per liter\[cells/L\]):0.90x(low) or 1.10x(high), Red Blood Cell(x10\^12 cells/L):0.93x(low) or 1.07x(high), neutrophil(%):0.65x(low) or 1.50x(high), White Blood Cell(x10\^9 cells/L):0.70x(low) or 1.60x(high). Participants were counted in the worst case if their laboratory value changes to low/within range or no change/high and were counted in the within range if their value was unchanged. Limits with 'x' are multipliers of central laboratory normal range.
Time frame: Up to Week 52
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb;to within range/nochange | 23 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb concentration (conc.);to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb conc;to within range/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb concentration;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle volume;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle volume;to within range/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle volume;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Monocytes;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Basophils;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Basophils;to within change/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Basophils;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Eosinophils;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Eosinophils;to within change/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Eosinophils;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hematocrit;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hematocrit;to within change/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hematocrit;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hemoglobin;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hemoglobin;to within range/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hemoglobin;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Lymphocytes;to low | 1 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Lymphocytes;to within range/no change | 23 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Lymphocytes;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle hemoglobin (Hb);to low | 1 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Monocytes;to within range/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Monocytes;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Platelet count;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Platelet count;to within range/no change | 23 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Platelet count;to high | 1 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Red blood cells;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Red blood cells;to within range/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Red blood cells;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Neutrophils;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Neutrophils;to within range/no change | 24 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Neutrophils;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | White blood cells;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | White blood cells;to within range/no change | 23 Participants |
| Placebo | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | White blood cells;to high | 1 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hemoglobin;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb;to within range/nochange | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Platelet count;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hemoglobin;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb concentration (conc.);to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Neutrophils;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb conc;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Lymphocytes;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle Hb concentration;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Red blood cells;to low | 1 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle volume;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Lymphocytes;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle volume;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | White blood cells;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle volume;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Lymphocytes;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Monocytes;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Red blood cells;to within range/no change | 24 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Basophils;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Mean corpuscle hemoglobin (Hb);to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Basophils;to within change/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Neutrophils;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Basophils;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Monocytes;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Eosinophils;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Red blood cells;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Eosinophils;to within change/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Monocytes;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Eosinophils;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | White blood cells;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hematocrit;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Platelet count;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hematocrit;to within change/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Neutrophils;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hematocrit;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Platelet count;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | Hemoglobin;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria | White blood cells;to low | 0 Participants |
Secondary
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Blood samples for liver function tests were collected at indicated time points. PCI ranges were, alanine aminotransferase (ALT) (units per liter\[U/L\]): \>=3x upper limit of normal (ULN) (high), alkaline phosphatase (alk phosp) (U/L): \>=2x ULN (high), aspartate amino transferase (AST) (U/L): \>=3x ULN (high), direct bilirubin (µmol/L): \>=2x ULN (high), total bilirubin (µmol/L): \>=2x ULN (high). Participants were counted in the worst case if their laboratory value changes to low, or within range or no change, or high. Participants were counted in within range if their value was unchanged. Limits with 'x' are multipliers of central laboratory normal range.
Time frame: Up to Week 52
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Alk phosp;to within range or no change | 26 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | AST;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | ALT;to within range or no change | 26 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Direct bilirubin;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Alk phosp;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Direct bilirubin;to within range/no change | 26 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Alk phosp;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Direct bilirubin;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | AST;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Total bilirubin;to low | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | ALT;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Total bilirubin;to within range/no change | 26 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | AST;to within range or no change | 26 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Total bilirubin;to high | 0 Participants |
| Placebo | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | ALT;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Total bilirubin;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | ALT;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | ALT;to within range or no change | 26 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | ALT;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Alk phosp;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Alk phosp;to within range or no change | 26 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Alk phosp;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | AST;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | AST;to within range or no change | 26 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | AST;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Direct bilirubin;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Direct bilirubin;to within range/no change | 26 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Direct bilirubin;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Total bilirubin;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria | Total bilirubin;to within range/no change | 26 Participants |
Secondary
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate and respiratory rate. Vital signs were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury): \<90 (low) or \>160 (high), DBP (millimeters of mercury): \<40 (low) or \>110 (high), heart rate (beats per minute): \<35 (low) or \>120 (high), respiration rate (breaths per minute): \<8 (low) or \>30 (high). Participants were counted in the worst-case category that their value changes to (low, within range or no change, or high), unless there was no change in their category. Participants whose value category were unchanged (high to high), or whose value became within range, were recorded in the 'to within range or no change' category.
Time frame: Up to Week 52
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | SBP;to low | 0 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | SBP;to within range or no change | 25 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | SBP;to high | 0 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | DBP;to low | 0 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | DBP;to within range or change | 25 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | DBP;to high | 0 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Heart rate;to low | 0 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Heart rate;to within range or no change | 25 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Heart rate;to high | 0 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Respiratory rate;to low | 0 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Respiratory rate;to within range/no change | 25 Participants |
| Placebo | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Respiratory rate;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Respiratory rate;to within range/no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | SBP;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Heart rate;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | SBP;to within range or no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Respiratory rate;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | SBP;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Heart rate;to within range or no change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | DBP;to low | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Respiratory rate;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | DBP;to within range or change | 25 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | Heart rate;to high | 0 Participants |
| DNX HBr 35 mg | Number of Participants With Worst-case Vital Signs Results by PCI Criteria | DBP;to high | 0 Participants |
Secondary
Number of SGRQ Responders
Response was defined as a SGRQ total score of 4 units below Baseline or lower. The SGRQ Questionnaire is a well-established, self-completed tool, with 50 questions comprising three domains; Symptoms, Activity, and Impacts scores (each ranging from 0 to 100). SGRQ total score was calculated by summing weights from all positive items, divided by sum of weights for all items in SGRQ questionnaire and multiplying by 100. The SGRQ total score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Number of SGRQ responders are presented.
Time frame: Weeks 12, 24 and 32
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of SGRQ Responders | Week 12, n=17,18 | 6 Participants |
| Placebo | Number of SGRQ Responders | Week 24, n=10,7 | 1 Participants |
| Placebo | Number of SGRQ Responders | Week 32, n=5,3 | 1 Participants |
| DNX HBr 35 mg | Number of SGRQ Responders | Week 12, n=17,18 | 5 Participants |
| DNX HBr 35 mg | Number of SGRQ Responders | Week 24, n=10,7 | 2 Participants |
| DNX HBr 35 mg | Number of SGRQ Responders | Week 32, n=5,3 | 1 Participants |
Secondary
Time to First Healthcare Resource Utilization (HCRU) Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
An exacerbation of COPD was defined by a worsening of symptoms requiring additional treatment or hospitalization. The date of onset of COPD exacerbations were planned to be recorded. This analysis was planned but data was not collected, as the study was terminated pre-maturely.
Time frame: Up to Week 52
Population: Safety Population. This analysis was planned but data was not collected, as the sample size was too small and study was terminated pre-maturely.