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Investigation of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of Oral Danirixin in Symptomatic COPD Subjects With Mild to Moderate Airflow Limitation at Risk for Exacerbations

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ClinicalTrials.gov Identifier: NCT02130193
Recruitment Status : Completed
First Posted : May 5, 2014
Results First Posted : May 18, 2017
Last Update Posted : July 2, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Danirixin
Drug: Placebo
Enrollment 102
Recruitment Details This was a 2 part study. In Part A, an open label, single arm, participants (par.) received danrixin 50 milligrams (mg) twice daily (BID) for 2 weeks. In Part B, a randomized (1:1), double-blind (sponsor unblinded) placebo controlled on top of standard of care study, par. received DNX 75 mg BID in one arm and placebo in the other arm for 52 weeks.
Pre-assignment Details A total of 19 par. in Part A were screened (10 failed) and 9 were randomized in a 2-week treatment period (TP) followed by a follow-up visit (FU) at 7- 14 days after last dose. A total of 127 par. in Part B were screened (34 failed) and 93 were randomized in a 52-week TP followed by a FU at 14- 28 days after last dose of the study.
Arm/Group Title Part A: 4-week Open-label Period: DNX 50 mg Part B: 52-week Double-blind Period: Placebo Part B: 52-week Double-blind Period: DNX 75 mg
Hide Arm/Group Description Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators). Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators). Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Period Title: Part A: 4-week Open-label Period
Started 9 0 0
Completed 9 0 0
Not Completed 0 0 0
Period Title: Part B: 52-week Double-blind Period
Started 0 48 45
Completed 0 38 37
Not Completed 0 10 8
Reason Not Completed
Adverse Event             0             5             3
Protocol Violation             0             2             1
Physician Decision             0             0             1
Withdrawal by Subject             0             3             3
Arm/Group Title Placebo DNX 75 mg Total
Hide Arm/Group Description Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators). Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators). Total of all reporting groups
Overall Number of Baseline Participants 48 45 93
Hide Baseline Analysis Population Description
Data for Part B is presented.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 45 participants 93 participants
58.8  (7.32) 62.4  (6.91) 60.5  (7.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 45 participants 93 participants
Female
25
  52.1%
23
  51.1%
48
  51.6%
Male
23
  47.9%
22
  48.9%
45
  48.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 48 participants 45 participants 93 participants
African American/African Heritage 1 0 1
White - White/Caucasian/European Heritage 47 45 92
1.Primary Outcome
Title Number of Participants With Any Adverse Event (AE) and, Serious Adverse Event (SAE) in Part A
Hide Description 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, events associated with liver injury and impaired liver function were categorized as SAE. Participants with any AE or SAE were summarized. Participants with AE or SAE occurrences >= 5 percent were summarized. All Subjects Population comprised of all participants who were screened and for whom a record existed on the study database.
Time Frame Up to Day 28 in Part A
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All Subjects Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: Participants
AE 5
SAEs 1
2.Primary Outcome
Title Number of Participants With Any AE and SAE in Part B
Hide Description 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, events associated with liver injury and impaired liver function were categorized as SAE. Participants with AE or SAE occurrences >= 5 percent were summarized.
Time Frame Up to Day 392 in Part B
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Hide Analysis Population Description
All Subjects Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Measure Type: Number
Unit of Measure: Participants
AE 25 25
SAEs 10 10
3.Primary Outcome
Title Number of Participants With Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Pulse Rate, Respiratory Rate and Body Temperature Abnormalities of Potential Clinical Importance in Part A
Hide Description Vital signs including SBP, DBP, pulse rate, respiratory rate and body temperature were taken on Day 1 pre-dose and on Day 14 and at Follow-up (Day 21 to 28) in Part A. Measurements were obtained in a semi-supine/ supine position after 5 minutes rest. The mean of replicate assessments at any given time point was used as the value for that time point. SBP <90 or >160 millimeter of mercury (mmHg); DBP <40 or >110 mmHg, pulse rate <35 or >120 beats per minute (bpm) and respiratory rate <8 or >30 breaths per minute were considered as values of potential clinical importance and were presented as 'High' or 'Low' values. Intent-to-Treat (ITT) Population comprised of all randomized par. who received at least one dose of study medication.
Time Frame Up to Day 28 in Part A
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Hide Analysis Population Description
ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: Participants
SBP, Day 14, low 0
SBP, Day 14, high 2
DBP, Day 14, low 0
DBP, Day 14, high 1
4.Primary Outcome
Title Number of Participants With Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Pulse Rate and Respiratory Rate Abnormalities of Potential Clinical Importance in Part B
Hide Description Vital signs including SBP, DBP, pulse rate and respiratory rate were taken on Day 1 pre-dose and on Day 28, 56, 112, 168, 280, 364 and at Follow-up (Day 378 to 392) in Part B. Measurements were obtained in a semi-supine/ supine position after 5 minutes rest. The mean of replicate assessments at any given time point was used as the value for that time point. SBP <90 or >160 mmHg, DBP <40 or >110 mmHg, pulse rate <35 or >120 bpm and respiratory rate <8 or >30 breaths per minute were considered as values of potential clinical importance and were presented as 'High' or 'Low' values. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Measure Type: Number
Unit of Measure: Participants
SBP, Day 1, low, n=48, 45 0 0
SBP, Day 1, high, n=48, 45 0 2
SBP, Day 28, low, n=47, 44 0 0
SBP, Day 28, high, n=47, 44 0 3
SBP, Day 56, low, n=46, 41 0 0
SBP, Day 56, high, n=46, 41 2 2
SBP, Day 112, low, n=46, 40 0 0
SBP, Day 112, high, n=46, 40 3 2
SBP, Day 168, low, n=44, 39 0 0
SBP, Day 168, high, n=44, 39 2 3
SBP, Day 280, low, n=39, 37 1 0
SBP, Day 280, high, n=39, 37 2 2
SBP, Day 364, low, n=39, 37 0 0
SBP, Day 364, high, n=39, 37 1 4
DBP, Day 280, low, n=39, 37 0 0
DBP, Day 280, high, n=39, 37 1 0
Respiratory rate, Day 1, low, n=48, 45 1 0
Respiratory rate, Day 1, high, n=48, 45 1 0
Respiratory rate, Day 56, low, n=46, 41 0 0
Respiratory rate, Day 56, high, n=46, 41 2 0
Respiratory rate, Day 112, low, n=46, 40 1 0
Respiratory rate, Day 112, high, n=46, 40 0 0
Respiratory rate, Day 168, low, n=44, 39 0 0
Respiratory rate, Day 168, high, n=44, 39 0 1
5.Primary Outcome
Title Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) in Part A
Hide Description 12-lead ECG was taken on Day 1 pre-dose and on Follow-up visit (Day 21 to 28) in Part A using an ECG machine. Triplicate reading were taken on Day 1 pre-dose. Participants with abnormal-clinically not significant (NCS) and abnormal-clinically significant (CS) findings were sumarized.
Time Frame Up to Day 28 in Part A
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ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: Participants
Abnormal-NCS, Day 1, pre-dose 3
Abnormal-CS, Day 1, pre-dose 0
Abnormal-NCS, Day 1, pre-dose 2 2
Abnormal-CS, Day 1, pre-dose 2 0
Abnormal-NCS, Day 1, pre-dose 3 2
Abnormal-CS, Day 1, pre-dose 3 0
6.Primary Outcome
Title Number of Participants With Abnormal 12-lead ECG in Part B
Hide Description 12-lead ECG was taken on Day 1 pre-dose and on Day 28, 168 and at Follow-up (Day 378 to 392) in Part B using an ECG machine. Participants with abnormal-NCS and abnormal-CS findings were sumarized. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
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Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Measure Type: Number
Unit of Measure: Participants
Abnormal-NCS, Day 28, n=47, 44 20 16
Abnormal-CS, Day 28, n=47, 44 0 1
Abnormal-NCS, Day 168, n=44, 38 15 11
Abnormal-CS, Day 168, n=44, 38 0 0
7.Primary Outcome
Title Number of Participants With Hematology Values of Potential Clinical Importance in Part A
Hide Description Blood samples were collected at Screening and Day 14 in Part A to evaluate hematology parameters which included hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count, platelet count and reticulocyte count. Hematology values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards.
Time Frame Up to Day 28 in Part A
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: Participants
RBC count, Day 14, low 1
Category title 2. RBC count, Day 14, high 0
8.Primary Outcome
Title Number of Participants With Hematology Values of Potential Clinical Importance in Part B
Hide Description Blood samples were collected at Screening and on Day 28, 168, and 364 in Part B to evaluate hematology parameters which included hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCHC, MCH, MCV, RBC count, WBC count, platelet count and reticulocyte count. Hematology values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Measure Type: Number
Unit of Measure: Participants
Platelet count, Day 28, low, n=46, 43 0 1
Platelet count, Day 28, high, n=46, 43 0 0
RBC count, Day 28, low, n=46, 43 0 1
RBC count, Day 28, high, n=46, 43 0 0
Platelet count, Day 168, low, n=43, 38 0 1
Platelet count, Day 168, high, n=43, 38 1 0
RBC count, Day 168, low, n=44, 38 2 1
RBC count, Day 168, high, n=44, 38 0 0
WBC count, Day 168, low, n=44, 38 0 0
WBC count, Day 168, high, n=44, 38 1 0
Platelet count, Day 364, low, n=39, 36 0 1
Platelet count, Day 364, high, n=39, 36 0 0
RBC count, Day 364, low, n=39, 36 2 1
RBC count, Day 364, high, n=39, 36 0 0
9.Primary Outcome
Title Number of Participants With Clinical Chemistry Values of Potential Clinical Importance in Part A
Hide Description Blood samples were collected at Screening and Day 14 in Part A to evaluate clinical chemistry parameters which included alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, calcium, bicarbonate, chloride, creatinine, direct bilirubin, gamma glutamyl transferase (GGT), glucose, potassium, total protein, sodium, blood urea nitrogen (BUN) and uric acid. Additional liver monitoring chemistry (ALT, AST, ALP and total and direct bilirubin) was done on Day 1 pre-dose. Clinical chemistry values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards.
Time Frame Up to Day 28 in Part A
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Hide Analysis Population Description
ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: Participants
GGT, Day 14, low 0
GGT, Day 14, high 2
Uric acid, Day 14, low 0
Uric acid, Day 14, high 8
10.Primary Outcome
Title Number of Participants With Clinical Chemistry Values of Potential Clinical Importance in Part B
Hide Description Blood samples were collected at Screening and on Day 28, 168 and 364 in Part B to evaluate clinical chemistry parameters which included ALT, albumin, ALP, AST, total bilirubin, calcium, bicarbonate, chloride, creatinine, direct bilirubin, GGT, glucose, potassium, total protein, sodium, BUN and uric acid. Clinical chemistry values of potential clinical importance were presented as 'High' or 'Low' values based on the reference laboratory standards. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Measure Type: Number
Unit of Measure: Participants
Creatinine, Day 28, low, n=47, 44 0 0
Creatinine, Day 28, high, n=47, 44 0 1
GGT, Day 28, low, n=47, 44 0 0
GGT, Day 28, high, n=47, 44 7 3
Uric acid, Day 28, low, n=47, 44 0 0
Uric acid, Day 28, high, n=47, 44 47 44
ALP, Day 84, low, n=46, 40 0 0
ALP, Day 84, high, n=46, 40 0 1
ALT, Day 84, low, n=46, 40 0 0
ALT, Day 84, high, n=46, 40 0 1
AST, Day 84, low, n=46, 40 0 0
AST, Day 84, high, n=46, 40 0 1
GGT, Day 168, low, n=43, 39 0 0
GGT, Day 168, high, n=43, 39 5 1
Uric acid, Day 168, low, n=43, 39 0 0
Uric acid, Day 168, high, n=43, 39 43 39
Direct bilirubin, Day 364, low, n=39, 37 0 0
Direct bilirubin, Day 364, high, n=39, 37 1 0
Total bilirubin, Day 364, low, n=39, 37 0 0
Total bilirubin, Day 364, high, n=39, 37 1 0
GGT, Day 364, low, n=39, 37 0 0
GGT, Day 364, high, n=39, 37 5 1
Uric acid, Day 364, low, n=39, 37 0 0
Uric acid, Day 364, high, n=39, 37 39 37
11.Primary Outcome
Title Number of Participants With Urinalysis Dipstick Results in Part A
Hide Description Test strip urinalysis was done for glucose, ketones, occult blood and protein at Screening and Day 14 in Part A. Results were presented as negative, trace, 1+, 2+ and 3+ for glucose, ketones, occult blood and protein. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Day 28 in Part A
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ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: Participants
Occult blood, Day 14, negative, n=9 9
Glucose, Day 14, negative, n=9 9
Ketones, Day 14, negative, n=9 9
Protein, Day 14, 1+, n=9 1
Protein, Day 14, negative, n=9 8
Urine microscopy-RBC, Day 14, not seen, n=1 1
Urine microscopy-WBC, Day 14, not seen, n=1 1
12.Primary Outcome
Title Number of Participants With Urinalysis Dipstick Results in Part B
Hide Description Test strip urinalysis was done for glucose, ketones, occult blood and protein at Screening and on Day 28, 168, 224 and 364 in Part B. Results were presented as negative, trace, 1+, 2+ and 3+ for glucose, ketones, occult blood and protein. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
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ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Measure Type: Number
Unit of Measure: Participants
Occult blood, Day 28, trace, n=47, 44 0 2
Occult blood, Day 28, 1+, n=47, 44 3 0
Occult blood, Day 28, negative, n=47, 44 44 42
Glucose, Day 28, trace, n=47, 44 0 1
Glucose, Day 28, 1+, n=47, 44 1 0
Glucose, Day 28, 3+, n=47, 44 0 2
Glucose, Day 28, negative, n=47, 44 46 41
Ketones, Day 28, trace, n=47, 44 3 2
Ketones, Day 28, negative, n=47, 44 44 42
Protein, Day 28, trace, n=47, 44 2 1
Protein, Day 28, 1+, n=47, 44 2 2
Protein, Day 28, negative, n=47, 44 43 41
Occult blood, Day 168, trace, n=42, 36 3 2
Occult blood, Day 168, 1+, n=42, 36 1 1
Occult blood, Day 168, 3+, n=42, 36 1 0
Occult blood, Day 168, negative, n=42, 36 37 33
Glucose, Day 168, 2+, n=42, 36 1 0
Glucose, Day 168, negative, n=42, 36 41 36
Ketones, Day 168, trace, n=42, 36 3 0
Ketones, Day 168, negative, n=42, 36 39 36
Protein, Day 168, trace, n=42, 36 2 1
Protein, Day 168, 1+, n=42, 36 1 2
Protein, Day 168, 2+, n=42, 36 1 0
Protein, Day 168, negative, n=42, 36 38 33
Occult blood, Day 224, negative, n=1, 0 1 0
Glucose, Day 224, negative, n=1, 0 1 0
Ketones, Day 224, negative, n=1, 0 1 0
Protein, Day 224, negative, n=1, 0 1 0
Occult blood, Day 364, trace, n=38, 36 3 2
Occult blood, Day 364, 1+, n=38, 36 2 1
Occult blood, Day 364, negative, n=38, 36 33 33
Glucose, Day 364, trace, n=38, 36 1 0
Glucose, Day 364, 2+, n=38, 36 1 0
Glucose, Day 364, negative, n=38, 36 36 36
Ketones, Day 364, trace, n=38, 36 3 0
Ketones, Day 364, negative, n=38, 36 35 36
Protein, Day 364, trace, n=38, 36 3 0
Protein, Day 364, 1+, n=38, 36 1 2
Protein, Day 364, 2+, n=38, 36 1 1
Protein, Day 364, negative, n=38, 36 33 33
13.Primary Outcome
Title Change From Baseline in Urine Power of Hydrogen (pH) at Day 14 in Part A
Hide Description Urinalysis including urine pH was done at Screening and Day 14 in Part A. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time Frame Up to Day 28 in Part A
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ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: pH
-0.06  (1.488)
14.Primary Outcome
Title Change From Baseline in Urine pH in Part B
Hide Description Urinalysis including urine pH was done at Screening and on Day 28, 168 and 364 in Part B. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
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ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Mean (Standard Deviation)
Unit of Measure: pH
Day 28, n=45, 43 -0.17  (0.648) -0.10  (0.552)
Day 168, n=40, 35 -0.18  (0.694) -0.13  (0.751)
Day 364, n=36, 35 -0.29  (0.731) -0.07  (0.768)
15.Primary Outcome
Title Change From Baseline in Urine Specific Gravity of Urine in Part A
Hide Description Urinalysis including urine specific gravity was done at Screening and Day 14 in Part A. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time Frame Up to Day 28 in Part A
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ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: urine specific gravity
-0.0008  (0.00817)
16.Primary Outcome
Title Change From Baseline in Urine Specific Gravity of Urine in Part B
Hide Description Urinalysis including urine specific gravity was done at Screening and on Day 28, 168 and 364 in Part B. Baseline was considered as the measurement obtained at Screening (Day -1). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Mean (Standard Deviation)
Unit of Measure: urine specific gravity
Day 28, n=45, 43 -0.0011  (0.00643) -0.0008  (0.00536)
Day 168, n=40, 35 -0.0012  (0.00771) -0.0002  (0.00748)
Day 364, n=36, 35 0.0004  (0.00569) 0.0013  (0.00561)
17.Primary Outcome
Title Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points in Part A
Hide Description FEV1 measures how much air a person can exhale during a forced breath in 1 second. FVC is the total amount of air exhaled during the FEV test. FEV1 and FVC were performed at Screening and on Day 1, 14 and at Follow-up visit (Day 21 to 28). FEV1 and FVC assessments at each time point (post-bronchodilator) were taken in triplicate. The maximum of the triplicate assessments were used. Baseline was considered as the measurement obtained at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Time Frame Up to Day 28 in Part A
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: Liter
FEV1, Day 14 0.0978  (0.10378)
FVC, Day 14 0.2233  (0.25407)
18.Primary Outcome
Title Change From Baseline in FEV1 and FVC at the Indicated Time Points in Part B
Hide Description FEV1 and FVC were performed at Screening and on Day 1, 28, 56, 112, 168, 280, 364 and at Follow-up (Day 378 to 392) in Part B. FEV1 and FVC assessments at each time point (post-bronchodilator) were taken in triplicate. The maximum of the triplicate assessments were used. Baseline was considered as the measurement obtained at Day 1 pre-dose. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Statistical analysis was performed using a repeated measures mixed effects model in a Bayesian framework. The estimate of the treatment difference and corresponding 95 percent credible interval was constructed for the difference between danirixin and placebo for each visit. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Mean (Standard Deviation)
Unit of Measure: Liter
FEV1, Day 28, n=47, 44 -0.018  (0.2049) 0.048  (0.1433)
FEV1, Day 56, n=46, 41 0.048  (0.3377) 0.017  (0.1633)
FEV1, Day 112, n=45, 39 0.011  (0.2431) 0.088  (0.3044)
FEV1, Day 168, n=44, 39 0.018  (0.2944) 0.015  (0.2129)
FEV1, Day 280, n=39, 37 -0.012  (0.3300) 0.043  (0.2310)
FEV1, Day 364, n=39, 37 -0.009  (0.2746) 0.028  (0.2988)
FVC, Day 28, n=47, 44 0.027  (0.3407) 0.022  (0.2845)
FVC, Day 56, n=46, 41 0.046  (0.4344) 0.036  (0.2706)
FVC, Day 112, n=45, 39 0.024  (0.4195) 0.014  (0.3714)
FVC, Day 168, n=44, 39 -0.061  (0.3956) -0.005  (0.3301)
FVC, Day 280, n=39, 37 -0.020  (0.5966) 0.041  (0.4271)
FVC, Day 364, n=39, 37 -0.021  (0.4290) 0.008  (0.4190)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.05 to 0.18
Parameter Dispersion
Type: Standard Deviation
Value: 0.06
Estimation Comments FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.05 to 0.18
Parameter Dispersion
Type: Standard Deviation
Value: 0.06
Estimation Comments FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.67
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.05 to 0.18
Parameter Dispersion
Type: Standard Deviation
Value: 0.06
Estimation Comments FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.05 to 0.18
Parameter Dispersion
Type: Standard Deviation
Value: 0.06
Estimation Comments FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.05 to 0.18
Parameter Dispersion
Type: Standard Deviation
Value: 0.06
Estimation Comments FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.05 to 0.18
Parameter Dispersion
Type: Standard Deviation
Value: 0.06
Estimation Comments FEV1, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.14
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.09
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.06 to 0.23
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.79
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.06 to 0.23
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.06 to 0.23
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.06 to 0.23
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.06 to 0.23
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.06 to 0.23
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.47
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.16 to 0.14
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.36
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.16 to 0.14
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.16 to 0.14
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.19
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.16 to 0.14
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.16 to 0.14
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.16 to 0.14
Parameter Dispersion
Type: Standard Deviation
Value: 0.07
Estimation Comments FEV1, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.11 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.14 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.14 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.50
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.14 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.14 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.14 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.14 to 0.20
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FEV1, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.19 to 0.13
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.19 to 0.13
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.19 to 0.13
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.19 to 0.13
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.19 to 0.13
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.19 to 0.13
Parameter Dispersion
Type: Standard Deviation
Value: 0.08
Estimation Comments FVC, Day 28. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.41
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.20 to 0.15
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.32
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.20 to 0.15
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.20 to 0.15
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.20 to 0.15
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 47
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.20 to 0.15
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 48
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.20 to 0.15
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 56. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 49
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.20 to 0.17
Parameter Dispersion
Type: Standard Deviation
Value: 0.10
Estimation Comments FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 50
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.20 to 0.17
Parameter Dispersion
Type: Standard Deviation
Value: 0.10
Estimation Comments FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 51
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.20 to 0.17
Parameter Dispersion
Type: Standard Deviation
Value: 0.10
Estimation Comments FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 52
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.20 to 0.17
Parameter Dispersion
Type: Standard Deviation
Value: 0.10
Estimation Comments FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 53
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.17
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.20 to 0.17
Parameter Dispersion
Type: Standard Deviation
Value: 0.10
Estimation Comments FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 54
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.20 to 0.17
Parameter Dispersion
Type: Standard Deviation
Value: 0.10
Estimation Comments FVC, Day 112. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 55
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.24
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 56
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.24
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 57
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.24
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 58
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.48
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.24
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 59
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.39
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.24
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 60
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.24
Parameter Dispersion
Type: Standard Deviation
Value: 0.09
Estimation Comments FVC, Day 168. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 61
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.15 to 0.32
Parameter Dispersion
Type: Standard Deviation
Value: 0.12
Estimation Comments FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 62
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.15 to 0.32
Parameter Dispersion
Type: Standard Deviation
Value: 0.12
Estimation Comments FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 63
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.15 to 0.32
Parameter Dispersion
Type: Standard Deviation
Value: 0.12
Estimation Comments FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 64
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.59
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.15 to 0.32
Parameter Dispersion
Type: Standard Deviation
Value: 0.12
Estimation Comments FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 65
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.53
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.15 to 0.32
Parameter Dispersion
Type: Standard Deviation
Value: 0.12
Estimation Comments FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 66
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.15 to 0.32
Parameter Dispersion
Type: Standard Deviation
Value: 0.12
Estimation Comments FVC, Day 280. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 67
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.68
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.28
Parameter Dispersion
Type: Standard Deviation
Value: 0.11
Estimation Comments FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 68
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.02 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.28
Parameter Dispersion
Type: Standard Deviation
Value: 0.11
Estimation Comments FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 69
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.55
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.04 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.28
Parameter Dispersion
Type: Standard Deviation
Value: 0.11
Estimation Comments FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 70
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.06 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.28
Parameter Dispersion
Type: Standard Deviation
Value: 0.11
Estimation Comments FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 71
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.08 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.28
Parameter Dispersion
Type: Standard Deviation
Value: 0.11
Estimation Comments FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 72
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.33
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is greater than 0.10 L is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.15 to 0.28
Parameter Dispersion
Type: Standard Deviation
Value: 0.11
Estimation Comments FVC, Day 364. Data presented are for 95% equal-tailed credible intervals
19.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Danirixin in Part A
Hide Description Cmax of danirixin was derived from the Pharmacokinetics (PK) samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A. PK analysis of danirixin was conducted by non-compartmental methods. PK Concenteration Population comprised of par. in the ITT Population and who had provided at least one on-treatment blood sample for determination of danirixin concentration.
Time Frame Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Geometric Mean (95% Confidence Interval)
Unit of Measure: Nanogram per milliliter (ng/mL)
Day 1 dose
397.785
(222.166 to 712.229)
Day 14 dose
512.576
(350.162 to 750.324)
20.Primary Outcome
Title Time of Occurrence of Cmax (Tmax) of Danirixin in Part A
Hide Description Tmax of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A. PK analysis of danirixin was conducted by non-compartmental methods.
Time Frame Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Median (Full Range)
Unit of Measure: Hour
Day 1 dose
1.017
(0.98 to 4.00)
Day 14 dose
2.000
(0.35 to 4.02)
21.Primary Outcome
Title Area Under the Blood Concentration-time Curve (AUC) Over Dosing Interval (AUC[0-12]) of Danirixin in Part A
Hide Description AUC (0-12) of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A. PK analysis of danirixin was conducted by non-compartmental methods. A Bayesian random effects model was performed adjusting for the trial as a random effect. A non-informative normal prior distribution was used. Point estimates and corresponding 90 percent credible intervals were constructed.
Time Frame Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 14 in Part A
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title DNX 50 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 50 mg BID with food and water for 2 weeks. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 9
Geometric Mean (95% Confidence Interval)
Unit of Measure: Hour*ng/mL
Day 1 dose
2203.522
(1303.851 to 3723.976)
Day 14 dose
2838.526
(1907.863 to 4223.171)
22.Primary Outcome
Title Number of Health Care Resource Utilization (HCRU) Defined COPD Exacerbations Per Year in Part B
Hide Description HCRU COPD exacerbations are defined as moderate or severe exacerbations based on requirement of new prescription antibiotics or oral corticosteroids, hospitalization or emergency room visits for management of COPD exacerbation. For par. with less than 364 days on-treatment, the annual exacerbation rate was imputed as the number of recorded on-treatment exacerbations, divided by the number of 4-week treatment period intervals for which the par. was in the study, multiplied by 13. For par. with 364 or more days on-treatment, the annual exacerbation rate was calculated as the number of recorded exacerbations between study days 1 and 364. Statistical analysis was done using a Bayesian Cox model, assuming a negative binomial distribution for the underlying exacerbation rate. The exacerbation rates along with the ratio (danirixin/placebo), were estimated and corresponding 95 percent credible intervals were produced using non-informative priors. 1 par. was excluded from the analysis.
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 23 20
Mean (Standard Deviation)
Unit of Measure: Exacerbations per year
2.9  (3.13) 3.2  (5.82)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.013
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
Method Bayesian Cox analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
0.92 to 4.43
Parameter Dispersion
Type: Standard Deviation
Value: 0.977
Estimation Comments Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
Method Bayesian Cox analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
0.92 to 4.43
Parameter Dispersion
Type: Standard Deviation
Value: 0.977
Estimation Comments Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.8 is presented.
Method Bayesian Cox analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
0.92 to 4.43
Parameter Dispersion
Type: Standard Deviation
Value: 0.977
Estimation Comments Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.7 is presented.
Method Bayesian Cox analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
0.92 to 4.43
Parameter Dispersion
Type: Standard Deviation
Value: 0.977
Estimation Comments Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.6 is presented.
Method Bayesian Cox analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
0.92 to 4.43
Parameter Dispersion
Type: Standard Deviation
Value: 0.977
Estimation Comments Data presented are for 95% equal-tailed credible intervals
23.Primary Outcome
Title Monthly Weighted Means of Exacerbations of Chronic Pulmonary Disease Tool-respiratory Symptoms (EXACT-RS) Total Score in Part B
Hide Description EXACT-RS is a tool which consists of 11 items from the 14 item EXACT- patient reported outcomes (EXACT-PRO) instrument, intended to capture information related to the respiratory symptoms of COPD, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness. The EXACT-RS has a scoring range of 0-40, higher scores indicate more severe symptoms. A par. had at least 10 days of diary data in any month to contribute a non-missing weighted mean AUC of daily values; otherwise the weighted mean for that month were considered missing. A mixed effects model in a Bayesian framework with repeated measures were performed on the EXACT-RS monthly weighted mean AUC data. The posterior mean and corresponding 95 percent credible interval were calculated. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 48 45
Mean (Standard Deviation)
Unit of Measure: Score on a scale
EXACT-RS, 1 month, n=48,45 12.4  (5.86) 11.8  (5.87)
EXACT-RS, 2 month, n=47,44 12.5  (6.67) 11.6  (6.31)
EXACT-RS, 3 month, n=46,41 12.5  (7.03) 10.5  (6.33)
EXACT-RS, 4 month, n=46,41 12.4  (6.97) 10.6  (6.61)
EXACT-RS, 5 month, n=46,40 12.0  (7.12) 10.6  (6.65)
EXACT-RS, 6 month, n=44,39 12.4  (7.34) 10.4  (6.14)
EXACT-RS, 7 month, n=44,39 12.3  (7.16) 10.3  (6.48)
EXACT-RS, 8 month, n=43,39 12.4  (7.3) 10.3  (6.93)
EXACT-RS, 9 month, n=40,38 12.2  (6.98) 10.7  (7.08)
EXACT-RS, 10 month, n=39,38 13.0  (7.14) 10.3  (7.09)
EXACT-RS, 11 month, n=39,37 12.2  (7.23) 10.5  (6.91)
EXACT-RS, 12 month, n=39,37 12.5  (7.08) 10.5  (7.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-2.81 to 2.17
Parameter Dispersion
Type: Standard Deviation
Value: 1.29
Estimation Comments EXACT-RS, 1 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.58
Confidence Interval (2-Sided) 95%
-3.11 to 2.37
Parameter Dispersion
Type: Standard Deviation
Value: 1.42
Estimation Comments EXACT-RS, 2 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.83
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -1.46
Confidence Interval (2-Sided) 95%
-4.43 to 1.45
Parameter Dispersion
Type: Standard Deviation
Value: 1.52
Estimation Comments EXACT-RS, 3 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -1.20
Confidence Interval (2-Sided) 95%
-4.07 to 1.90
Parameter Dispersion
Type: Standard Deviation
Value: 1.53
Estimation Comments EXACT-RS, 4 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.96
Confidence Interval (2-Sided) 95%
-3.82 to 2.28
Parameter Dispersion
Type: Standard Deviation
Value: 1.56
Estimation Comments EXACT-RS, 5 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -0.93
Confidence Interval (2-Sided) 95%
-4.01 to 2.26
Parameter Dispersion
Type: Standard Deviation
Value: 1.58
Estimation Comments EXACT-RS, 6 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.73
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -1.00
Confidence Interval (2-Sided) 95%
-4.15 to 2.09
Parameter Dispersion
Type: Standard Deviation
Value: 1.58
Estimation Comments EXACT-RS, 7 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.81
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -1.48
Confidence Interval (2-Sided) 95%
-4.71 to 1.76
Parameter Dispersion
Type: Standard Deviation
Value: 1.69
Estimation Comments EXACT-RS, 8 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -1.23
Confidence Interval (2-Sided) 95%
-4.66 to 2.22
Parameter Dispersion
Type: Standard Deviation
Value: 1.75
Estimation Comments EXACT-RS, 9 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.91
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -2.26
Confidence Interval (2-Sided) 95%
-5.66 to 0.99
Parameter Dispersion
Type: Standard Deviation
Value: 1.74
Estimation Comments EXACT-RS, 10 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.71
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -1.05
Confidence Interval (2-Sided) 95%
-4.73 to 2.13
Parameter Dispersion
Type: Standard Deviation
Value: 1.73
Estimation Comments EXACT-RS, 11 month. Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0 is presented.
Method Bayesian analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value -1.35
Confidence Interval (2-Sided) 95%
-4.77 to 2.04
Parameter Dispersion
Type: Standard Deviation
Value: 1.74
Estimation Comments EXACT-RS, 12 month. Data presented are for 95% equal-tailed credible intervals
24.Secondary Outcome
Title Cmax of Danirixin in Part B
Hide Description Cmax of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B. PK analysis of danirixin was conducted by non-compartmental methods. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title DNX 75 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 45
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
Day 1 dose, n=44
517.784
(388.207 to 690.612)
Day 364 dose, n=36
756.391
(554.011 to 1032.700)
25.Secondary Outcome
Title Tmax of Danirixin in Part B
Hide Description Tmax of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B. PK analysis of danirixin was conducted by non-compartmental methods. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title DNX 75 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 45
Median (Full Range)
Unit of Measure: Hour
Day 1 dose, n=44
2.000
(0.48 to 6.00)
Day 364 dose, n=36
1.100
(0.50 to 10.00)
26.Secondary Outcome
Title AUC(0-12) of Danirixin in Part B
Hide Description AUC (0-12) of danirixin was derived from the PK samples collected at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B. PK analysis of danirixin was conducted by non-compartmental methods. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Pre-dose and at 0.5, 1, 2, 4, 6, 8, 10 and 12 hour post-dose on Day 1 and Day 364; and at pre-dose and 2 hours on Day 28, 56 and 168 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title DNX 75 mg
Hide Arm/Group Description:
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 45
Geometric Mean (95% Confidence Interval)
Unit of Measure: Hour*ng/mL
Day 1 dose, n=44
2388.303
(1834.420 to 3109.425)
Day 364 dose, n=36
4366.995
(3254.122 to 5860.458)
27.Secondary Outcome
Title Number of EXACT-PRO Exacerbations Per Year in Part B
Hide Description EXACT-PRO is a 14 item patient reported outcome instrument designed to capture information on the occurrence, frequency, severity, and duration of COPD exacerbations. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. For par. with less than 364 days on-treatment, the annual exacerbation rate was imputed as the number of recorded on-treatment exacerbations, divided by the number of 4-week treatment period intervals for which the par. was in the study, multiplied by 13. For par. with 364 or more days on-treatment, the annual exacerbation rate was calculated as the number of recorded exacerbations between study days 1 and 364. Statistical analysis was done using a Bayesian Cox model, assuming a negative binomial distribution for the underlying exacerbation rate. The exacerbation rates and the ratio (danirixin/placebo), were estimated and 95 percent credible intervals were produced using non-informative priors. 1 par. was excluded from analysis.
Time Frame Up to Day 392 in Part B
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Placebo DNX 75 mg
Hide Arm/Group Description:
Participants received one tablet of placebo twice daily with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Participants received one immediate release tablet of danirixin (DNX) 75 mg BID with food and water for 52 weeks. It was administered on top of the participant's current standard of care. Participants were permitted to continue taking inhaled maintenance medications. Rescue medications for acute symptoms were also permitted (e.g. short acting bronchodilators).
Overall Number of Participants Analyzed 27 28
Mean (Standard Deviation)
Unit of Measure: Exacerbations per year
3.6  (2.75) 3.3  (3.47)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 1.0 is presented.
Method Bayesian Cox analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.71 to 1.63
Parameter Dispersion
Type: Standard Deviation
Value: 0.242
Estimation Comments Data presented are for 95% equal-tailed credible intervals
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, DNX 75 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.138
Comments Posterior probability that the treatment difference (DNX 75 mg-placebo) is less than 0.9 is presented.
Method Bayesian Cox analysis
Comments P-value is actually a posterior probability.
Method of Estimation Estimation Parameter Posterior mean difference
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.71 to 1.63
Parameter Dispersion
Type: Standard Deviation
Value: 0.242
Estimation Comments Data presented are for 95% equal-tailed credible intervals