Trial Outcomes & Findings for A Pilot Study of Danirixin for Disease Progression in Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT03170232)
NCT ID: NCT03170232
Last Updated: 2020-07-31
Results Overview
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.
TERMINATED
PHASE2
54 participants
Up to Week 52
2020-07-31
Participant Flow
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).
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.
Participant milestones
| Measure |
Placebo
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
27
|
27
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
27
|
27
|
Reasons for withdrawal
| Measure |
Placebo
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Study closed/terminated
|
26
|
23
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Pilot Study of Danirixin for Disease Progression in Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
Placebo
n=27 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=27 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
Total
n=54 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.0 Years
STANDARD_DEVIATION 6.88 • n=5 Participants
|
66.1 Years
STANDARD_DEVIATION 5.86 • n=7 Participants
|
66.1 Years
STANDARD_DEVIATION 6.33 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White- White/Caucasian/European Heritage
|
22 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Week 52Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=26 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=26 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Rate of Decline in Forced Expiratory Volume in One Second (FEV1)
|
-132.8 Milliliters per year
Standard Error 110.75
|
-200.0 Milliliters per year
Standard Error 115.01
|
PRIMARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32Population: Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=18 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
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
|
3.92 Scores on a scale
Standard Deviation 9.527
|
|
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
|
-0.41 Scores on a scale
Standard Deviation 7.673
|
|
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
|
0.49 Scores on a scale
Standard Deviation 9.679
|
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population
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.
Outcome measures
| Measure |
Placebo
n=27 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=27 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs)
AEs
|
9 Participants
|
14 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Event (SAEs)
SAEs
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=24 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=25 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Basophils;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Basophils;to within change/no change
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Basophils;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Eosinophils;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Eosinophils;to within change/no change
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Eosinophils;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Hematocrit;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Hematocrit;to within change/no change
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Hematocrit;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Hemoglobin;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Hemoglobin;to within range/no change
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Hemoglobin;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Lymphocytes;to low
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Lymphocytes;to within range/no change
|
23 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Lymphocytes;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle hemoglobin (Hb);to low
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle Hb;to within range/nochange
|
23 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle Hb;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle Hb concentration (conc.);to low
|
0 Participants
|
0 Participants
|
|
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
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle Hb concentration;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle volume;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle volume;to within range/no change
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Mean corpuscle volume;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Monocytes;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Monocytes;to within range/no change
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Monocytes;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Platelet count;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Platelet count;to within range/no change
|
23 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Platelet count;to high
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Red blood cells;to low
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Red blood cells;to within range/no change
|
24 Participants
|
24 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Red blood cells;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Neutrophils;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Neutrophils;to within range/no change
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Neutrophils;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
White blood cells;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
White blood cells;to within range/no change
|
23 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
White blood cells;to high
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=26 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=26 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Calcium;to within range or no change;n=25,25
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Calcium;to low;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Calcium;to high;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Bicarbonate;to low;n=25,25
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Bicarbonate;to within range or no change;n=25,25
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Bicarbonate;to high;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Chloride, to low;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Chloride, to within range or no change;n=25,25
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Chloride, to high;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Creatinine;to low;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Creatinine;to within range or no change;n=25,25
|
24 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Creatinine;to high;n=25,25
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Glucose;to low;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Glucose;to within range or no change;n=25,25
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Glucose;to high;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Potassium;to low;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Potassium;to within range or no change;n=25,25
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Potassium;to high;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Sodium;to low;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Sodium;to within range or no change;n=25,25
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Sodium;to high;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Total protein;to low;n=26,26
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Total protein;to within range/no change;n=26,26
|
26 Participants
|
26 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
Total protein;to high;n=26,26
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
BUN;to low;n=25,25
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
BUN;to within range or no change;n=25,25
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst Case Clinical Chemistry Results by PCI Criteria
BUN;to high;n=25,25
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=26 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=26 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
ALT;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
ALT;to within range or no change
|
26 Participants
|
26 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
ALT;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Alk phosp;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Alk phosp;to within range or no change
|
26 Participants
|
26 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Alk phosp;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
AST;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
AST;to within range or no change
|
26 Participants
|
26 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
AST;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Direct bilirubin;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Direct bilirubin;to within range/no change
|
26 Participants
|
26 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Direct bilirubin;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Total bilirubin;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Total bilirubin;to within range/no change
|
26 Participants
|
26 Participants
|
|
Number of Participants With Worst Case Liver Function Tests Results by PCI Criteria
Total bilirubin;to high
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population. This analysis was planned but data was not collected, as study was terminated pre-maturely.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 4, 12 and 24Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=25 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate
Week 4;n=25,25
|
-0.7 Beats per minute
Standard Deviation 8.61
|
0.5 Beats per minute
Standard Deviation 6.50
|
|
Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate
Week 12;n=17,19
|
-2.8 Beats per minute
Standard Deviation 5.43
|
1.5 Beats per minute
Standard Deviation 9.93
|
|
Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate
Week 24;n=10,8
|
-0.7 Beats per minute
Standard Deviation 6.14
|
1.2 Beats per minute
Standard Deviation 7.85
|
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 4, 12 and 24Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=25 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
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
|
0.4 Milliseconds
Standard Deviation 16.29
|
|
Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals
PR interval;Week 12;n=17,19
|
1.8 Milliseconds
Standard Deviation 12.40
|
-3.3 Milliseconds
Standard Deviation 15.83
|
|
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
|
-3.2 Milliseconds
Standard Deviation 12.79
|
|
Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals
QRS interval;Week 4;n=25,25
|
-1.3 Milliseconds
Standard Deviation 4.90
|
0.0 Milliseconds
Standard Deviation 5.40
|
|
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
|
-3.0 Milliseconds
Standard Deviation 4.42
|
|
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
|
0.5 Milliseconds
Standard Deviation 5.11
|
|
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
|
-3.7 Milliseconds
Standard Deviation 16.78
|
|
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
|
-9.9 Milliseconds
Standard Deviation 45.86
|
|
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 17.00
|
8.2 Milliseconds
Standard Deviation 21.84
|
|
Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals
QTc interval;Week 4;n=3,8
|
-1.9 Milliseconds
Standard Deviation 6.30
|
0.1 Milliseconds
Standard Deviation 13.96
|
|
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
|
-21.4 Milliseconds
Standard Deviation 62.39
|
|
Change From Baseline in ECG Parameters: PR, QRS, QT and QTc Intervals
QTc interval;Week 24;n=1,3
|
-7.0 Milliseconds
Standard Deviation NA
NA indicates standard deviation could not be calculated as a single participant was analyzed.
|
4.4 Milliseconds
Standard Deviation 9.05
|
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=25 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=25 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
SBP;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
SBP;to within range or no change
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
SBP;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
DBP;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
DBP;to within range or change
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
DBP;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
Heart rate;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
Heart rate;to within range or no change
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
Heart rate;to high
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
Respiratory rate;to low
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
Respiratory rate;to within range/no change
|
25 Participants
|
25 Participants
|
|
Number of Participants With Worst-case Vital Signs Results by PCI Criteria
Respiratory rate;to high
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population. This analysis was planned but data was not collected, as the sample size was too small and study was terminated pre-maturely.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 52Population: Safety Population. This analysis was planned but data was not collected, as the sample size was too small and study was terminated pre-maturely.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 2, 4, 8, 12, 16, 20, 24, 32 and 40Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=26 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=25 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Change From Baseline in FEV1
Week 40;n=3,1
|
-0.2907 Liters
Standard Deviation 0.09209
|
-0.2010 Liters
Standard Deviation NA
NA indicates standard deviation could not be calculated as a single participant was analyzed.
|
|
Change From Baseline in FEV1
Week 2;n=26,25
|
0.0383 Liters
Standard Deviation 0.23206
|
-0.0152 Liters
Standard Deviation 0.11936
|
|
Change From Baseline in FEV1
Week 4;n=25,25
|
-0.0309 Liters
Standard Deviation 0.16173
|
0.0038 Liters
Standard Deviation 0.15194
|
|
Change From Baseline in FEV1
Week 8;n=18,20
|
-0.0375 Liters
Standard Deviation 0.18245
|
-0.0251 Liters
Standard Deviation 0.19673
|
|
Change From Baseline in FEV1
Week 12;n=18,19
|
-0.0744 Liters
Standard Deviation 0.12213
|
-0.0014 Liters
Standard Deviation 0.20688
|
|
Change From Baseline in FEV1
Week 16;n=14,15
|
-0.0515 Liters
Standard Deviation 0.16156
|
-0.0480 Liters
Standard Deviation 0.23974
|
|
Change From Baseline in FEV1
Week 20;n=14,11
|
-0.0197 Liters
Standard Deviation 0.19092
|
-0.0939 Liters
Standard Deviation 0.11837
|
|
Change From Baseline in FEV1
Week 24;n=10,8
|
0.0030 Liters
Standard Deviation 0.19217
|
-0.1301 Liters
Standard Deviation 0.16956
|
|
Change From Baseline in FEV1
Week 32;n=5,3
|
-0.1964 Liters
Standard Deviation 0.11034
|
-0.1340 Liters
Standard Deviation 0.32707
|
SECONDARY outcome
Timeframe: Weeks 12, 24 and 32Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=18 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Number of SGRQ Responders
Week 32, n=5,3
|
1 Participants
|
1 Participants
|
|
Number of SGRQ Responders
Week 12, n=17,18
|
6 Participants
|
5 Participants
|
|
Number of SGRQ Responders
Week 24, n=10,7
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=18 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Change From Baseline in SGRQ Symptoms Score
Week 12;n=17,18
|
-2.56 Scores on a scale
Standard Deviation 8.525
|
-0.86 Scores on a scale
Standard Deviation 22.513
|
|
Change From Baseline in SGRQ Symptoms Score
Week 24;n=10,7
|
-6.25 Scores on a scale
Standard Deviation 17.246
|
-7.34 Scores on a scale
Standard Deviation 29.528
|
|
Change From Baseline in SGRQ Symptoms Score
Week 32;n=5,3
|
1.71 Scores on a scale
Standard Deviation 18.006
|
-2.07 Scores on a scale
Standard Deviation 36.896
|
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=18 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Change From Baseline in SGRQ Activity Score
Week 12;n=17,18
|
-1.89 Scores on a scale
Standard Deviation 7.882
|
2.69 Scores on a scale
Standard Deviation 11.732
|
|
Change From Baseline in SGRQ Activity Score
Week 24;n=10,7
|
2.09 Scores on a scale
Standard Deviation 11.085
|
-0.91 Scores on a scale
Standard Deviation 8.750
|
|
Change From Baseline in SGRQ Activity Score
Week 32;n=5,3
|
2.89 Scores on a scale
Standard Deviation 9.690
|
-2.44 Scores on a scale
Standard Deviation 16.520
|
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=17 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=18 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Change From Baseline in SGRQ Impacts Score
Week 12;n=17,18
|
2.36 Scores on a scale
Standard Deviation 9.801
|
6.07 Scores on a scale
Standard Deviation 11.255
|
|
Change From Baseline in SGRQ Impacts Score
Week 24;n=10,7
|
4.65 Scores on a scale
Standard Deviation 6.255
|
2.01 Scores on a scale
Standard Deviation 8.003
|
|
Change From Baseline in SGRQ Impacts Score
Week 32;n=5,3
|
1.45 Scores on a scale
Standard Deviation 11.983
|
3.04 Scores on a scale
Standard Deviation 3.778
|
SECONDARY outcome
Timeframe: Baseline (Day 1 pre-dose), Weeks 12, 24 and 32Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=17 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Change From Baseline in COPD Assessment Test (CAT) Score
Week 12;n=16,17
|
-1.5 Scores on a scale
Standard Deviation 5.42
|
2.6 Scores on a scale
Standard Deviation 5.68
|
|
Change From Baseline in COPD Assessment Test (CAT) Score
Week 24;n=10,6
|
-1.5 Scores on a scale
Standard Deviation 5.46
|
0.7 Scores on a scale
Standard Deviation 6.15
|
|
Change From Baseline in COPD Assessment Test (CAT) Score
Week 32;n=4,3
|
2.0 Scores on a scale
Standard Deviation 4.08
|
5.3 Scores on a scale
Standard Deviation 3.51
|
SECONDARY outcome
Timeframe: 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 45-48Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=23 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=25 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
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
|
1.9 Percentage of days
Standard Deviation 20.42
|
|
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
|
3.0 Percentage of days
Standard Deviation 25.88
|
|
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
|
3.3 Percentage of days
Standard Deviation 26.54
|
|
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
|
2.0 Percentage of days
Standard Deviation 30.49
|
|
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
|
2.3 Percentage of days
Standard Deviation 35.00
|
|
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
|
-4.8 Percentage of days
Standard Deviation 38.88
|
|
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
|
-4.9 Percentage of days
Standard Deviation 40.02
|
|
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
|
10.0 Percentage of days
Standard Deviation 46.71
|
|
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
|
3.0 Percentage of days
Standard Deviation 72.22
|
|
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
|
-0.5 Percentage of days
Standard Deviation 77.88
|
|
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
|
-21.4 Percentage of days
Standard Deviation NA
NA indicates standard deviation could not be calculated as a single participant was analyzed.
|
|
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 0.0
|
—
|
SECONDARY outcome
Timeframe: 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 45-48Population: Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).
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.
Outcome measures
| Measure |
Placebo
n=23 Participants
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=25 Participants
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
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
|
-0.11 Number of puffs per day
Standard Deviation 0.887
|
|
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
|
-0.30 Number of puffs per day
Standard Deviation 1.223
|
|
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
|
-0.34 Number of puffs per day
Standard Deviation 1.433
|
|
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
|
-0.36 Number of puffs per day
Standard Deviation 1.785
|
|
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
|
0.08 Number of puffs per day
Standard Deviation 1.738
|
|
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
|
0.24 Number of puffs per day
Standard Deviation 1.149
|
|
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
|
0.22 Number of puffs per day
Standard Deviation 1.260
|
|
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
|
-0.33 Number of puffs per day
Standard Deviation 1.201
|
|
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
|
-0.23 Number of puffs per day
Standard Deviation 1.724
|
|
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
|
-0.06 Number of puffs per day
Standard Deviation 1.959
|
|
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
|
0.43 Number of puffs per day
Standard Deviation NA
NA indicates standard deviation could not be calculated as a single participant was analyzed.
|
|
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 0.00
|
—
|
Adverse Events
Placebo
DNX HBr 35 mg
Serious adverse events
| Measure |
Placebo
n=27 participants at risk
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=27 participants at risk
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Nervous system disorders
Syncope
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
General disorders
Death
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
Other adverse events
| Measure |
Placebo
n=27 participants at risk
Participants received one tablet of placebo with food twice daily for 52 weeks.
|
DNX HBr 35 mg
n=27 participants at risk
Participants received one tablet of DNX HBr 35 mg with food twice daily for 52 weeks.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
7.4%
2/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
7.4%
2/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Infections and infestations
Upper respiratory tract infection
|
7.4%
2/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Infections and infestations
Ear infection
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Infections and infestations
Gastroenteritis viral
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Infections and infestations
Oral candidiasis
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
7.4%
2/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Gastrointestinal disorders
Abdominal pain
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Gastrointestinal disorders
Nausea
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Vascular disorders
Hypertension
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
7.4%
2/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
General disorders
Oedema peripheral
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
General disorders
Fatigue
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Investigations
Blood glucose increased
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Investigations
Haematocrit decreased
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Investigations
Haemoglobin decreased
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Investigations
Mean cell volume decreased
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Eye disorders
Eye pain
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Reproductive system and breast disorders
Gynaecomastia
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Nervous system disorders
Headache
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Skin and subcutaneous tissue disorders
Perioral dermatitis
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
3.7%
1/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
0.00%
0/27 • Non-SAEs and SAEs were reported from start of study treatment and up to 52 weeks
Non-SAE and SAEs are reported for Safety Population.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER