Clinical Trial Results:
Randomized double blind (sponsor unblind) study evaluating the effect of 14 days of treatment with danirixin (GSK1325756) on neutrophil extracellular traps (NETs) formation in participants with stable chronic obstructive pulmonary disease (COPD)
Summary
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EudraCT number |
2017-001069-25 |
Trial protocol |
GB |
Global end of trial date |
08 Oct 2018
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Results information
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Results version number |
v2(current) |
This version publication date |
02 Nov 2019
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First version publication date |
21 Sep 2019
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Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
207551
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Apr 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Oct 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess the change from baseline in NETs formation in participants with COPD following 14 days treatment with danirixin hydrobromide (HBr) 35 milligram (mg) twice daily
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Nov 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 19
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Worldwide total number of subjects |
19
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EEA total number of subjects |
19
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
8
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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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
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Screening 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. | |||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Investigator, Subject | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||
Arm description |
Participants received one tablet of matching placebo twice daily orally with food for 14 days. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received one tablet of matching placebo twice daily orally with food for 14 days.
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Arm title
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Danirixin hydrobromide 35 mg | |||||||||
Arm description |
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Danirixin hydrobromide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received one tablet of danirixin hydrobromide 35 mg twice daily orally with food for 14 days.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received one tablet of matching placebo twice daily orally with food for 14 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Danirixin hydrobromide 35 mg
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Reporting group description |
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received one tablet of matching placebo twice daily orally with food for 14 days. | ||
Reporting group title |
Danirixin hydrobromide 35 mg
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Reporting group description |
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days. |
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End point title |
Percentage change from Baseline in sputum neutrophil extracellular traps (NETs) quantified by Histone-Elastase Complexes [1] | ||||||||||||||||||
End point 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). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Primary
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End point timeframe |
Baseline (Day 1), Day 7 and Day 14
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical analysis to report. |
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Notes [2] - Primary Completer Population. [3] - Primary Completer Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in sputum NETs quantified by deoxyribonucleic acid (DNA)-elastase complexes | ||||||||||||||||||
End point 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. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Day 7 and Day 14
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Notes [4] - Primary Completer Population. [5] - Primary Completer Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in percentage of microscope field area occupied by sputum NETs | ||||||||||||||||||
End point 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. Only those participants with data available at the specified data points were analyzed. 99999 indicates data was not collected because 7 days treatment was insufficient to observe the changes in the sputum NETs via microscopy.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Day 7 and Day 14
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Notes [6] - Primary Completer Population. [7] - Primary Completer Population. |
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No statistical analyses for this end point |
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End point title |
Number of participants with adverse events (AEs) and serious adverse events (SAEs) | |||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Up to Day 21
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Notes [8] - Modified Intent-to-Treat Population. [9] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) | ||||||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Day 7 and Day 14
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Notes [10] - Modified Intent-to-Treat Population. [11] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in heart rate | ||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Day 7 and Day 14
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Notes [12] - Modified Intent-to-Treat Population. [13] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in respiration rate | ||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Day 7 and Day 14
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Notes [14] - Modified Intent-to-Treat Population. [15] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia’s Formula (QTcF) | ||||||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [16] - Modified Intent-to-Treat Population. [17] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Spirometry: Forced expiratory volume in one second (FEV1) at indicated time points | ||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 14
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Notes [18] - Modified Intent-to-Treat Population. [19] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Spirometry: Forced vital capacity (FVC) at indicated time points | ||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Day 1 and Day 14
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Notes [20] - Modified Intent-to-Treat Population. [21] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils, White Blood Cell (WBC) count | |||||||||||||||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [22] - Modified Intent-to-Treat Population. [23] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in hematology parameter: Hematocrit | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [24] - Modified Intent-to-Treat Population. [25] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in hematology parameter: Hemoglobin | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [26] - Modified Intent-to-Treat Population. [27] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in hematology parameter: Mean Corpuscular Volume | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [28] - Modified Intent-to-Treat Population. [29] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in hematology parameter: Mean Corpuscular Hemoglobin | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [30] - Modified Intent-to-Treat Population. [31] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in hematology parameter: Red Blood Cell count | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [32] - Modified Intent-to-Treat Population. [33] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in chemistry parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) | |||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [34] - Modified Intent-to-Treat Population. [35] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in chemistry parameters: Calcium, Glucose, Potassium, Sodium, Urea | |||||||||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [36] - Modified Intent-to-Treat Population. [37] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in chemistry parameters: Creatinine, Direct Bilirubin, Total Bilirubin | |||||||||||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [38] - Modified Intent-to-Treat Population. [39] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in urinalysis parameter: Specific Gravity | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [40] - Modified Intent-to-Treat Population. [41] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in urinalysis parameter: Potential of hydrogen (pH) | ||||||||||||
End point 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.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Day 14
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Notes [42] - Modified Intent-to-Treat Population. [43] - Modified Intent-to-Treat Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in sputum resistin levels | ||||||||||||||||||
End point 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. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Day 7 and Day 14
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Notes [44] - Primary Completer Population. [45] - Primary Completer Population. |
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No statistical analyses for this end point |
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End point title |
Change from Baseline in the ratio of sputum NETs to sputum neutrophils | ||||||||||||
End point 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. Only those participants with data available at the specified data points were analyzed.
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End point type |
Secondary
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||||||||||||
End point timeframe |
Baseline (Day 1) and Day 14
|
||||||||||||
|
|||||||||||||
Notes [46] - Primary Completer Population. [47] - Primary Completer Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in sputum elastase activity | ||||||||||||||||||
End point 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. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline (Day 1), Day 7 and Day 14
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [48] - Primary Completer Population. [49] - Primary Completer Population. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Change from Baseline in peripheral blood neutrophil NETs formation quantified by DNA release | ||||||||||||||||||
End point 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.Phorbol12-myristate 13-acetate(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 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 Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Only those participants with data available at the specified data points were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Day 14
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [50] - Modified Intent-to-Treat Population. [51] - Modified Intent-to-Treat Population. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Percentage change from Baseline in peripheral blood neutrophil NETs formation quantified by microscopy | ||||||||||||||||||
End point 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). 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.Only those participants with data available at the specified data points were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline (Day 1) and Day 14
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [52] - Modified Intent-to-Treat Population. [53] - Modified Intent-to-Treat Population. |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Maximum observed concentration (Cmax) of danirixin [54] | ||||||||||||
End point 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). Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
|
||||||||||||
Notes [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period. |
|||||||||||||
|
|||||||||||||
Notes [55] - PK Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to Cmax (Tmax) of danirixin [56] | ||||||||||||
End point description |
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
|
||||||||||||
Notes [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period. |
|||||||||||||
|
|||||||||||||
Notes [57] - PK Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Area under the blood concentration-time curve [AUC(0-t)] of danirixin [58] | ||||||||||||
End point description |
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t). Only those participants with data available at the specified data points were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
|
||||||||||||
Notes [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period. |
|||||||||||||
|
|||||||||||||
Notes [59] - PK Population. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time of last observed concentration (Tlast) of danirixin [60] | ||||||||||||
End point description |
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
|
||||||||||||
Notes [60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period. |
|||||||||||||
|
|||||||||||||
Notes [61] - PK Population. |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
AEs and SAEs were collected from start of the treatment up to Day 21
|
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Adverse event reporting additional 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.
|
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.1
|
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Reporting groups
|
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Reporting group title |
Danirixin hydrobromide 35 mg
|
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Reporting group description |
Participants received one tablet of danirixin hydrobromide 35 milligram (mg) twice daily orally with food for 14 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
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Reporting group description |
Participants received one tablet of matching placebo twice daily orally with food for 14 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |