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Randomized Study Evaluating the Effect of Danirixin on Neutrophil Extracellular Traps (NETs) in Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT03250689
Recruitment Status : Terminated (Study terminated due to a change in the benefit-risk profile for danirixin in COPD.)
First Posted : August 16, 2017
Results First Posted : November 8, 2019
Last Update Posted : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Danirixin
Drug: Placebo
Drug: Rescue medication
Drug: Inhaled COPD maintenance medication
Enrollment 19
Recruitment Details The study was conducted at single center in United Kingdom. This study was terminated early due to a change in the benefit risk profile of danirixin observed in another study NCT03034967, leading to cessation of the overall danirixin development program.
Pre-assignment Details A total of 43 participants were screened, of which 23 were screen failures (23 participants did not meet inclusion/exclusion criteria). From the 20 participants who passed screening, 1 was not randomized due to study being terminated early. Hence, 19 participants were enrolled and received treatment in this study.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description Participants received one tablet of matching placebo twice daily orally with food for 14 days. Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Period Title: Overall Study
Started 5 14
Completed 5 14
Not Completed 0 0
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg Total
Hide Arm/Group Description Participants received one tablet of matching placebo twice daily orally with food for 14 days. Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days. Total of all reporting groups
Overall Number of Baseline Participants 5 14 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 14 participants 19 participants
61.6  (6.02) 65.3  (7.03) 64.3  (6.82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 14 participants 19 participants
Female
2
  40.0%
6
  42.9%
8
  42.1%
Male
3
  60.0%
8
  57.1%
11
  57.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 14 participants 19 participants
White: White/Caucasian/European Heritage
5
 100.0%
14
 100.0%
19
 100.0%
1.Primary Outcome
Title Percentage Change From Baseline in Sputum Neutrophil Extracellular Traps (NETs) Quantified by Histone-Elastase Complexes
Hide Description Sputum samples were collected at indicated time points to assess NET formation via histone elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value. Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by 100. Analysis was performed using a mixed effect repeated measures model with covariates of treatment group, log(Baseline NETs) and treatment group by day interaction. The response variable was the log of the ratio of post-Baseline NETs to Baseline NETs. Primary completer population consisted of all participants in the Modified Intent-To-Treat population who had completed the assessments supporting the primary endpoint (sputum NETs).
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 3 8
Mean (95% Confidence Interval)
Unit of Measure: Percent change
Day 7, n=3,6 Number Analyzed 3 participants 6 participants
-3.2
(-77.0 to 306.6)
-9.4
(-64.4 to 130.6)
Day 14, n=3,8 Number Analyzed 3 participants 8 participants
-30.5
(-71.7 to 70.7)
-13.6
(-49.1 to 46.5)
2.Secondary Outcome
Title Change From Baseline in Sputum NETs Quantified by Deoxyribonucleic Acid (DNA)-Elastase Complexes
Hide Description Sputum samples were collected at indicated time points to assess NET formation via DNA elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 3 8
Mean (Standard Error)
Unit of Measure: Units per milliliter
Day 7, n=3,6 Number Analyzed 3 participants 6 participants
1.83  (4.610) 0.63  (1.859)
Day 14, n=3,8 Number Analyzed 3 participants 8 participants
-4.53  (2.696) 2.08  (4.072)
3.Secondary Outcome
Title Change From Baseline in Percentage of Microscope Field Area Occupied by Sputum NETs
Hide Description Sputum samples were collected at indicated time points and NETs area was quantified by microscopy. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Completer Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 2 7
Mean (Standard Error)
Unit of Measure: Percentage of microscope field area
Day 7 NA [1]   (NA) NA [1]   (NA)
Day 14 0.900  (0.9200) -0.259  (0.5183)
[1]
Data was not collected because 7 days treatment was insufficient to observe the changes in the sputum NETs via microscopy.
4.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment such as important medical events 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 to prevent one of the other outcomes, Modified Intent-to-Treat Population consisted of all randomized participants who received at least one dose of study treatment.
Time Frame Up to Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
3
  60.0%
6
  42.9%
SAEs
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description SBP and DBP were measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury
SBP, Day 7 -11.2  (17.01) -4.1  (17.70)
SBP, Day 14 -1.4  (16.10) -5.3  (15.77)
DBP, Day 7 -2.2  (9.91) -2.1  (10.34)
DBP, Day 14 2.6  (11.01) -5.3  (7.98)
6.Secondary Outcome
Title Change From Baseline in Heart Rate
Hide Description Heart rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 7 6.8  (6.02) 1.6  (11.28)
Day 14 4.0  (6.89) 0.1  (6.86)
7.Secondary Outcome
Title Change From Baseline in Respiration Rate
Hide Description Respiration rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Breaths per minute
Day 7 -0.6  (1.95) 1.8  (2.67)
Day 14 0.2  (0.84) 2.1  (3.43)
8.Secondary Outcome
Title Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)
Hide Description Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Milliseconds
PR Interval 7.6  (20.44) -4.8  (15.69)
QRS Duration -0.3  (1.12) 0.5  (5.55)
QT Interval -4.8  (10.05) 3.7  (15.67)
QTcF Interval -4.6  (0.38) -1.6  (5.96)
9.Secondary Outcome
Title Spirometry: Forced Expiratory Volume in One Second (FEV1) at Indicated Time Points
Hide Description FEV1 is the amount of air that can be forcefully exhaled from the lungs in the first second of a forced exhalation. It was measured by spirometry test. Mean and standard deviation data of FEV1 measured at Day 1 and Day 14 have been presented.
Time Frame Day 1 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Liter
Day 1 2.458  (0.6331) 1.914  (0.7267)
Day 14 2.344  (0.7174) 1.910  (0.7428)
10.Secondary Outcome
Title Spirometry: Forced Vital Capacity (FVC) at Indicated Time Points
Hide Description FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Mean and standard deviation data of FVC measured at Day 1 and Day 14 have been presented.
Time Frame Day 1 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Liter
Day 1 4.026  (1.2021) 3.416  (1.1304)
Day 14 4.036  (1.3992) 3.369  (1.1456)
11.Secondary Outcome
Title Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Counts, Total Neutrophils, White Blood Cell (WBC) Count
Hide Description Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils and WBC count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Giga cells per liter
Basophils 0.00  (0.000) -0.02  (0.058)
Eosinophils 0.040  (0.0686) -0.020  (0.0609)
Lymphocytes -0.20  (0.316) -0.08  (0.269)
Monocytes -0.04  (0.114) 0.02  (0.080)
Platelets counts 8.2  (18.94) -7.9  (41.66)
Total neutrophils -0.38  (0.965) 0.29  (0.943)
WBC count -0.56  (0.948) 0.16  (1.075)
12.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Hematocrit
Hide Description Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Percentage of red blood cells in blood
-0.0058  (0.02279) -0.0115  (0.02085)
13.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Hemoglobin
Hide Description Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Grams per liter
-2.2  (6.72) -5.4  (7.99)
14.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Mean Corpuscular Volume
Hide Description Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Volume. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Femtoliter
0.06  (1.339) 0.31  (1.263)
15.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin
Hide Description Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Picograms
-0.08  (0.920) -0.22  (0.749)
16.Secondary Outcome
Title Change From Baseline in Hematology Parameter: Red Blood Cell Count
Hide Description Blood samples were collected to analyze the hematology parameter: Red Blood Cell count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Trillion cells per liter
-0.070  (0.2081) -0.154  (0.2171)
17.Secondary Outcome
Title Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)
Hide Description Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: International units per liter
ALT -1.6  (4.39) -1.9  (8.24)
ALP 2.8  (6.26) 1.3  (13.89)
AST -0.6  (2.61) -3.1  (2.11)
18.Secondary Outcome
Title Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Urea
Hide Description Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Millimoles per liter
Calcium -0.032  (0.0782) -0.034  (0.0947)
Glucose 0.36  (0.635) 0.12  (0.398)
Potassium -0.12  (0.148) 0.06  (0.287)
Sodium 0.0  (1.58) 0.2  (2.04)
Urea -0.42  (0.867) 0.26  (0.777)
19.Secondary Outcome
Title Change From Baseline in Chemistry Parameters: Creatinine, Direct Bilirubin, Total Bilirubin
Hide Description Blood samples were collected to analyze the chemistry parameters: Creatinine, Direct Bilirubin and Total Bilirubin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter
Creatinine 2.6  (5.86) 1.2  (6.99)
Direct Bilirubin -0.4  (0.55) 0.7  (1.65)
Total Bilirubin 0.8  (0.84) -1.2  (3.26)
20.Secondary Outcome
Title Change From Baseline in Urinalysis Parameter: Specific Gravity
Hide Description Urinary specific gravity measurement is a part of routine urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: Unitless
0.0030  (0.00908) 0.0046  (0.00887)
21.Secondary Outcome
Title Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)
Hide Description Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 14
Mean (Standard Deviation)
Unit of Measure: pH
1.00  (1.225) -0.25  (0.672)
22.Secondary Outcome
Title Change From Baseline in Sputum Resistin Levels
Hide Description Sputum samples were collected at indicated time points to analyze resistin levels. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 3 8
Mean (Standard Error)
Unit of Measure: Nanograms per milliliter
Day 7, n=3,6 Number Analyzed 3 participants 6 participants
8.93  (15.513) -2.01  (4.629)
Day 14, n=3,8 Number Analyzed 3 participants 8 participants
15.28  (27.619) 2.61  (2.711)
23.Secondary Outcome
Title Change From Baseline in the Ratio of Sputum NETs to Sputum Neutrophils
Hide Description Sputum samples were collected to calculate ratio of sputum NETs to sputum neutrophils. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value. The ratio is calculated as the sputum NETs divided by the number of sputum neutrophils.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Completer Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 2 7
Mean (Standard Error)
Unit of Measure: Ratio
0.5200  (0.41000) 0.4557  (0.53149)
24.Secondary Outcome
Title Change From Baseline in Sputum Elastase Activity
Hide Description Sputum samples were collected at indicated time points to analyze sputum elastase activity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1), Day 7 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Completer Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 3 8
Mean (Standard Error)
Unit of Measure: Nanograms per milliliter
Day 7, n=3,6 Number Analyzed 3 participants 6 participants
638.0  (381.36) 238.0  (224.50)
Day 14, n=3,8 Number Analyzed 3 participants 8 participants
411.3  (439.20) 66.1  (45.64)
25.Secondary Outcome
Title Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by DNA Release
Hide Description Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by DNA release. DNA-elastase complexes quantified NETs formation. Phorbol 12-myristate 13-acetate (PMA) was used to induce inflammation and NETs formation in the PMA stimulated samples. Blood from participants were tested at Baseline and Day 14 for non-PMA stimulated samples, and at Baseline and Day 14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally (non PMA induced) or where NETs formation was already raised (PMA stimulated). Hence participants were counted in both the categories - PMA stimulated and not PMA stimulated. NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time Frame Baseline (Day 1) and Day 14
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Hide Analysis Population Description
Modified Intent-to-Treat Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 5 12
Mean (Standard Error)
Unit of Measure: Relative fluorescence units
Not PMA stimulated 3044.8  (4251.78) -721.1  (731.82)
PMA stimulated -96.8  (9418.43) -1211.0  (5102.21)
26.Secondary Outcome
Title Percentage Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by Microscopy
Hide Description Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by microscopy.DNA-elastase complexes quantified NETs formation.PMA was used to induce inflammation and NETs formation in PMA stimulated samples. Blood from participants were tested at Baseline and Day14 for non-PMA stimulated samples,and at Baseline and Day14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally(non PMA induced)or where NETs formation was already raised(PMA stimulated).Participants were counted in both categories-PMA stimulated and not PMA stimulated.NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA.Baseline was considered as Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by100.
Time Frame Baseline (Day 1) and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Modified Intent-to-Treat Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 4 11
Mean (Standard Error)
Unit of Measure: Percent change
Not PMA stimulated 927.5  (585.03) 560.5  (395.72)
PMA stimulated 44.7  (41.79) 90.6  (60.33)
27.Secondary Outcome
Title Maximum Observed Concentration (Cmax) of Danirixin
Hide Description Blood samples were collected to evaluate the pharmacokinetic (PK) of danirixin at the indicated time points for the analysis of Cmax. PK population consisted of all participants in the Modified Intent-To-Treat population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values).
Time Frame Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter
Day 1, n=14 Number Analyzed 14 participants
855.2
(52.29%)
Day 14, n=13 Number Analyzed 13 participants
1135.2
(65.73%)
28.Secondary Outcome
Title Time to Cmax (Tmax) of Danirixin
Hide Description Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax.
Time Frame Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 14
Median (Full Range)
Unit of Measure: Hours
Day 1, n=14 Number Analyzed 14 participants
1.000
(0.50 to 4.00)
Day 14, n=13 Number Analyzed 13 participants
1.000
(0.50 to 4.00)
29.Secondary Outcome
Title Area Under the Blood Concentration-time Curve [AUC(0-t)] of Danirixin
Hide Description Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t).
Time Frame Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the specified data points were analyzed.
Arm/Group Title Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours * nanograms per milliliter
Day 1
2173.4
(39.57%)
Day 14
2751.1
(51.24%)
30.Secondary Outcome
Title Time of Last Observed Concentration (Tlast) of Danirixin
Hide Description Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast.
Time Frame Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Arm/Group Title Danirixin Hydrobromide 35 mg
Hide Arm/Group Description:
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
Overall Number of Participants Analyzed 14
Median (Full Range)
Unit of Measure: Hours
Day 1, n=14 Number Analyzed 14 participants
4.000
(4.00 to 4.05)
Day 14, n=13 Number Analyzed 13 participants
4.000
(4.00 to 4.00)
Time Frame AEs and SAEs were collected from start of the treatment up to Day 21
Adverse Event Reporting Description AEs and SAEs were collected for modified Intent-to-Treat Population which consisted of all randomized participants who received at least one dose of study treatment.
 
Arm/Group Title Placebo Danirixin Hydrobromide 35 mg
Hide Arm/Group Description Participants received one tablet of matching placebo twice daily orally with food for 14 days. Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days.
All-Cause Mortality
Placebo Danirixin Hydrobromide 35 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)      0/14 (0.00%)    
Hide Serious Adverse Events
Placebo Danirixin Hydrobromide 35 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/5 (0.00%)      0/14 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Danirixin Hydrobromide 35 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/5 (60.00%)      6/14 (42.86%)    
Gastrointestinal disorders     
Dry mouth  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Gastrooesophageal reflux disease  1  0/5 (0.00%)  0 1/14 (7.14%)  1
Nausea  1  0/5 (0.00%)  0 1/14 (7.14%)  1
Vomiting  1  0/5 (0.00%)  0 1/14 (7.14%)  1
General disorders     
Catheter site haematoma  1  0/5 (0.00%)  0 1/14 (7.14%)  1
Malaise  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Peripheral swelling  1  0/5 (0.00%)  0 1/14 (7.14%)  1
Injury, poisoning and procedural complications     
Procedural complication  1  0/5 (0.00%)  0 1/14 (7.14%)  1
Metabolism and nutrition disorders     
Decreased appetite  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Myalgia  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Nervous system disorders     
Dysgeusia  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Migraine  1  0/5 (0.00%)  0 1/14 (7.14%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/5 (20.00%)  1 1/14 (7.14%)  1
Dyspnoea  1  1/5 (20.00%)  1 1/14 (7.14%)  1
Sputum increased  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Skin and subcutaneous tissue disorders     
Night sweats  1  1/5 (20.00%)  1 0/14 (0.00%)  0
Pruritus  1  0/5 (0.00%)  0 1/14 (7.14%)  1
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03250689    
Other Study ID Numbers: 207551
2017-001069-25 ( EudraCT Number )
First Submitted: August 11, 2017
First Posted: August 16, 2017
Results First Submitted: August 29, 2019
Results First Posted: November 8, 2019
Last Update Posted: November 8, 2019