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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03034967
Registration number
NCT03034967
Ethics application status
Date submitted
25/01/2017
Date registered
27/01/2017
Date last updated
28/10/2020
Titles & IDs
Public title
Danirixin Dose Ranging Study in Participants With Chronic Obstructive Pulmonary Disease (COPD)
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Scientific title
Randomised, Double-Blind (Sponsor Open), Placebo-Controlled, Multicentre, Dose Ranging Study to Evaluate the Efficacy and Safety of Danirixin Tablets Administered Twice Daily Compared With Placebo for 24 Weeks in Adult Participants With Chronic Obstructive Pulmonary Disease (COPD)
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Secondary ID [1]
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2016-003675-21
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Secondary ID [2]
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205724
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive
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Condition category
Condition code
Respiratory
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Chronic obstructive pulmonary disease
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Danirixin
Treatment: Drugs - Danirixin matching placebo
Treatment: Drugs - Standard of care
Treatment: Drugs - Rescue medication
Experimental: Danirixin 5 mg - Eligible participants will receive danirixin 5 mg tablet with food twice daily along with standard care of treatment for 24 weeks.
Experimental: Danirixin 10 mg - Eligible participants will receive danirixin 10 mg tablet with food twice daily along with standard care of treatment for 24 weeks.
Experimental: Danirixin 25 mg - Eligible participants will receive danirixin 25 mg tablet with food twice daily along with standard care of treatment for 24 weeks.
Experimental: Danirixin 35 mg - Eligible participants will receive danirixin 35 mg tablet with food twice daily along with standard care of treatment for 24 weeks.
Experimental: Danirixin 50 mg - Eligible participants will receive danirixin 50 mg tablet with food twice daily along with standard care of treatment for 24 weeks.
Placebo Comparator: Placebo - Eligible participants will receive placebo tablet with food twice daily along with standard care of treatment for 24 weeks.
Treatment: Drugs: Danirixin
Danirixin is available as 5, 10, 25, 35 and 50 mg white, film-coated, oval or round shaped tablets for oral administration.
Treatment: Drugs: Danirixin matching placebo
Danirixin matching placebo will be available as white, film-coated, oval or round shaped tablets for oral administration.
Treatment: Drugs: Standard of care
Participants will continue with their standard of care inhaled medications (i.e. long acting bronchodilators with or without inhaled corticosteroids) during the study treatment.
Treatment: Drugs: Rescue medication
Participants will continue to use rescue medication(s). The following rescue medications may be used: short acting beta agonists, short acting muscarinic antagonists, or short acting combination bronchodilators.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Change From Baseline in Respiratory Symptoms Measured by Evaluating Respiratory Symptoms (E-RS) in COPD. E-RS: COPD Total Score
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Assessment method [1]
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E-RS: COPD is a subset of Exacerbations of Chronic pulmonary Disease Tool (EXACT). E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Per protocol population included all participants from the mITT population who did not have a protocol deviation considered to impact efficacy. Posterior mean change and standard deviation has been presented.
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Timepoint [1]
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Baseline and Month 6
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Primary outcome [2]
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Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Breathlessness Score)
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Assessment method [2]
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E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: RS-BRL comprised of 5 items, score range (0-17), RS-CSP comprised of 3 items, score range (0-11), and RS-CSY comprised of 3 items, score range (0-12). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
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Timepoint [2]
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Baseline and Month 6
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Primary outcome [3]
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Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Cough and Sputum Score)
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Assessment method [3]
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E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: RS-BRL comprised of 5 items, score range (0-17), RS-CSP comprised of 3 items, score range (0-11), and RS-CSY comprised of 3 items, score range (0-12). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
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Timepoint [3]
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Baseline and Month 6
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Primary outcome [4]
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Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Chest Symptoms Score)
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Assessment method [4]
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E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. The domains include: RS-BRL comprised of 5 items, score range (0-17), RS-CSP comprised of 3 items, score range (0-11), and RS-CSY comprised of 3 items, score range (0-12). The total score ranged between 0-40 and higher values indicates severe respiratory symptoms. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
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Timepoint [4]
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Baseline and Month 6
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Primary outcome [5]
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Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
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Assessment method [5]
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AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
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Timepoint [5]
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Up to Day 196
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Primary outcome [6]
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Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI)
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Assessment method [6]
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Blood samples were collected from participants for analysis of following hematology parameters with PCI low and high values: Basophils % (High 5.00x), Eosinophils % (High 2.00x), Mean corpuscular hemoglobin concentration (MCHC) gram per deciliter (g/dL) (Low 0.85x, high 1.10x), Mean corpuscular hemoglobin (MCH) picograms (pg) (Low 0.85x, high 1.20x), Mean corpuscular volume (MCV) femtoliter (fL) (low 0.25x, high 2.00x), Erythrocytes (Ery.)(10^12cells/L) (Low 0.93x, high 1.07x), Hematocrit (Ratio of 1) (Low 0.50x, high 0.50x), Hemoglobin gram per liter (g/L) (Low 0.85x, high 1.20x), Leukocytes (x10^9/L) (Low 0.70x, high 1.60x), Lymphocytes % (Low 0.80x, high 1.20x), Monocytes % (Low 0.80x, high 1.60x), Neutrophils % (Low 0.65x, high 1.50x), Platelets (x10^9cells/L) (Low 0.90x, high 1.10x). Multipliers are identified by "x", otherwise actual comparison values are provided with units. Values above and below this range were considered of PCI.
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Timepoint [6]
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Up to Day 196
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Primary outcome [7]
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Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI
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Assessment method [7]
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Blood samples were collected from participants for analysis of following chemistry parameters with PCI low and high values: Alanine aminotransferase (ALT) International units per liter (IU/L) (High => 3x ULN), Alkaline phosphatase (ALP) (IU/L) (High = 2x ULN); Aspartate aminotransferase (AST) (IU/L) (High=> 3x ULN); Bilirubin micromole per liter (umol/L) (High = 2x ULN); Calcium millimole per liter (mmol/L) (Low 0.85x, high 1.08x), Chloride (mmol/L) (Low 0.90x, high 1.10x), Creatinine (umol/L) (High 1.30x), Direct bilirubin (umol/L) (High = 2x ULN), Glucose (mmol/L) (Low <0.6x, high >4x), Potassium (mmol/L) (Low 0.75x, high 1.30x); Protein (g/L) (High 1.25x), Sodium (mmol/L) (Low 0.80x, high 1.15x), Multipliers are identified by "x", otherwise actual comparison values are provided with units. Values above and below this range were considered of PCI.
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Timepoint [7]
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Up to Day 196
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Primary outcome [8]
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Number of Participants With Worst Case Vital Signs Parameter Results by PCI
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Assessment method [8]
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Vital signs parameters includes systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate and respiration rate were measured in a semi-supine position after 5 minutes rest for the participants at indicated time points. PCI ranges for vital signs parameters were as follows: <90 to >160 millimeters of mercury (mmHg) for SBP and <40 to >110 mmHg for DBP, <35 or >120 beats per minute for heart rate and <8 or >30 breaths per minute for respiration rate. Values above and below this range were considered of PCI.
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Timepoint [8]
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Up to Day 168
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Primary outcome [9]
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Number of Participants With Worst Case Post-Baseline Abnormal 12-lead Electrocardiogram (ECG) Findings
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Assessment method [9]
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Triplicate 12-lead ECG obtained to measure PR, QRS, QT, and Corrected QT intervals. Only those participants with worst case post-Baseline data have been represented for abnormal - not clinical significant and abnormal - clinical significant. Day 1 was considered as Baseline.
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Timepoint [9]
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Baseline and Day 168
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Secondary outcome [1]
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Number of Moderate or Severe Healthcare Resource Utilization (HCRU) Exacerbations Per Participant
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Assessment method [1]
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Participants with moderate or severe COPD exacerbations, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness analyzed. Mild exacerbations are defined as exacerbations that did not require treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization, Emergency Room [ER] visit or resulting in death). Moderate exacerbations are defined as exacerbations that required treatment with oral/systemic corticosteroids and/or antibiotics (not involving hospitalization, ER visit or resulting in death). Severe exacerbations are defined as exacerbations that required hospitalization, ER visit or resulted in death. Number of moderate or severe HCRU exacerbations per participant has been presented, where 0= participants in each treatment group who did not experience an event; 1= participants in each treatment group who experienced 1 event and >=2= participants in each treatment group who experienced 2 or more events.
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Timepoint [1]
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Up to Day 196
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Secondary outcome [2]
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Number of Responders E-RS in COPD (E-RS): COPD Total Score
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Assessment method [2]
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E-RS: COPD is a subset of EXACT. E-RS is a tool that consists of 11 items from the 14 item EXACT instrument. E-RS is intended to capture information related to the respiratory symptoms of COPD, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness. The E-RS has a scoring range of 0-40; higher scores indicate more severe symptoms. Response is defined as an E-RS: COPD total score of 2 units below baseline or lower. Non-response is defined as an E-RS: COPD total score higher than 2 units below Baseline.
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Timepoint [2]
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Month 6
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Secondary outcome [3]
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Number of EXACT Events Per Participant
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Assessment method [3]
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EXACT is a 14 item patient reported outcome (PRO) instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. Events were categorized as recovered, censored, or persistent worsening. Number of EXACT events per participant has been presented, where 0= participants in each treatment group who did not experience an event; 1= participants in each treatment group who experienced 1 event and >=2= participants in each treatment group who experienced 2 or more events.
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Timepoint [3]
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Up to Day 196
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Secondary outcome [4]
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Time to First EXACT Event
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Assessment method [4]
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The time to first on-treatment EXACT event was calculated as the onset date of the first on-treatment EXACT event minus date of start of treatment plus 1.
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Timepoint [4]
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Up to Day 168
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Secondary outcome [5]
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Severity of EXACT Event
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Assessment method [5]
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EXACT is a 14 item PRO instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. Severity is the highest EXACT total score during the period from onset to recovery.
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Timepoint [5]
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Up to Day 168
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Secondary outcome [6]
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EXACT Event Duration for All Events
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Assessment method [6]
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EXACT is a 14 item PRO instrument designed to capture information on the occurrence, frequency, severity, and duration of exacerbations of disease in participants with COPD. The total score for EXACT-PRO ranges from 0-100, higher scores indicate more severe symptoms. Severity is the highest EXACT total score during the period from onset to recovery. Duration of EXACT events has been reported.
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Timepoint [6]
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Up to Day 168
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Secondary outcome [7]
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Time to First HCRU-defined COPD Exacerbation
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Assessment method [7]
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The time to first on-treatment Moderate/Severe HCRU exacerbation was calculated as exacerbation onset date of first on-treatment moderate or severe on-treatment exacerbation - date of start of treatment +1.
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Timepoint [7]
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Up to Day 196
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Secondary outcome [8]
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Time to First Severe HCRU-defined COPD Exacerbation
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Assessment method [8]
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A COPD exacerbation defined as a severe exacerbation if it requires hospitalization or ER visit or extended observation. The time to first on-treatment Moderate/Severe HCRU exacerbation was calculated as exacerbation onset date of first on-treatment moderate or severe on-treatment exacerbation - date of start of treatment +1.
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Timepoint [8]
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Up to Day 196
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Secondary outcome [9]
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HCRU-defined Exacerbation Duration
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Assessment method [9]
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The duration of HCRU exacerbation were determined. The duration of the exacerbation was calculated as (exacerbation resolution date or date of death - exacerbation onset date + 1). For exacerbations which were not resolved but where the participant later died from other causes, the duration was calculated using date of death as the end date of the event.
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Timepoint [9]
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Up to Day 196
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Secondary outcome [10]
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Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score
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Assessment method [10]
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The SGRQ-C consists of 40 items aggregated into 3 component scores: Symptoms, Activity, Impacts, and a Total score. Each response to a question is assigned a weight. Component scores are calculated by summing the weights from all positive items in that component, dividing by the sum of weights for all items in that component, and multiplying this number by 100. Component scores could range from 0-100, with a higher component score indicating greater disease burden. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
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Timepoint [10]
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Baseline, Days 84 and 168
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Secondary outcome [11]
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Number of SGRQ Responder
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Assessment method [11]
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A participant was consider Responder according to SGRQ total score if their change from Baseline SGRQ total score of 4 units below Baseline or lower.
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Timepoint [11]
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Day 84 and Day 168
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Secondary outcome [12]
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Change From Baseline COPD Assessment Test (CAT) Total Score
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Assessment method [12]
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The CAT is an 8 item questionnaire (cough, sputum, chest tightness, breathlessness, going up hills/stairs, activity limitation at home, confidence leaving the home, and sleep and energy) that measures health status of participants with COPD. Participants were completed each question by rating their experience on a 6 point scale ranging from 0 (maximum impairment) to 5 (no impairment) with a total scoring range of 0-40; higher scores indicate worse health status. A CAT score was calculated by summing the non-missing scores on the eight items. Individual items are scored from 0 to 5 with a total score range from 0 - 40, higher scores indicate greater disease impact. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Posterior mean change and standard deviation has been presented.
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Timepoint [12]
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Baseline, Days 84 and 168
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Secondary outcome [13]
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Number of CAT Responder
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Assessment method [13]
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A participant was considered as a responder according to CAT score if their change from Baseline CAT score 2.0 units below Baseline or lower.
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Timepoint [13]
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Day 84 and Day 168
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Secondary outcome [14]
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Change From Baseline in Post-bronchodilator FEV1 as a Lung Function Assessment
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Assessment method [14]
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Spirometric analysis was done to determine FEV1. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Least square mean change from Baseline and standard error has been presented.
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Timepoint [14]
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0
Baseline, Days 84 and 168
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Secondary outcome [15]
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Percent Predicted Normal FEV1
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Assessment method [15]
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Spirometric analysis was done to determine percent predicted FEVI at screening. FEV1 is forced expiratory volume in one second. Percent predicted FEV1 is defined as the percent FEV1 of the participant is divided by average FEV1 percent in the population of any person similar age, sex and body composition.
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Timepoint [15]
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At Screening
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Secondary outcome [16]
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Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) as a Lung Function Assessment
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Assessment method [16]
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Spirometric analysis was done to determine FVC. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Least square mean change from Baseline and standard error has been presented.
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Timepoint [16]
0
0
Baseline, Days 84 and 168
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Secondary outcome [17]
0
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Change From Baseline in Post-bronchodilator FEV1/FVC Ratio as a Lung Function Assessment
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Assessment method [17]
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Spirometric analysis was done to determine FEV1 and FVC. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
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Timepoint [17]
0
0
Baseline, Days 84 and 168
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Secondary outcome [18]
0
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Change From Baseline Number of Puffs of Rescue Medication Per Day
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Assessment method [18]
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The mean number of puffs of rescue per day was calculated over the same time periods and using the same assumptions as rescue use via diary. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Least square mean change from Baseline and standard error has been presented.
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Timepoint [18]
0
0
Baseline, Months 1, 2, 3, 4, 5 and 6
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Secondary outcome [19]
0
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Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire
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Assessment method [19]
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The Clinical Visit PROactive Physical Activity in COPD (C-PPAC) tool is a designed for intermittent use within a clinical study. PROactive Total Score and two domain scores (amount and difficulty) are derived using data from the C-PPAC questionnaire and a physical activity monitor worn for 7 days prior to the questionnaire.C-PPAC is a 12 item questionnaire. The PROactive tools are scored from 0 to 100 with higher scores indicating greater disease impact. It was implemented in a subset of approximately 50% of participants. The amount domain is calculated using 2 items from the C-PPAC questionnaire (amount of walking outside and chores outside) and 2 activity monitor outputs (vector magnitude units per minute (VMU/min) and steps/day). Each domain score is based on the addition of items (0-15 for amount and 0-40 for difficulty) and then scaled from 0-100. The total score is calculated as (amount+difficulty)/2.
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Timepoint [19]
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Days 84 and 168
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Secondary outcome [20]
0
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Danirixin Whole Blood Pharmacokinetic Concentration-Time Data
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Assessment method [20]
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Blood samples were collected from the participants for the analysis of blood pharmacokinetic concentration-time data. All participants in the mITT population who had at least 1 non-missing Pharmacokinetic assessment obtained and analyzed whilst on treatment with danirixin were included Pharmacokinetic population.
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Timepoint [20]
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Pre-dose on Days 1, 56, 84 and 168; 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Days 1 and 168
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Secondary outcome [21]
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Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] of Danirixin in Whole Blood Using Dried Blood Spot
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Assessment method [21]
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Blood samples were collected at indicated timepoints for the analysis of phamacokinetic parameter. All participants in the PK population who had at least 1 non-missing PK assessment obtained and analyzed whilst on treatment with danirixin from a dry blood spot sample and corresponding wet whole blood sample were included in Pharmacokinetic population.
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Timepoint [21]
0
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Days 1 and 168
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Secondary outcome [22]
0
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Concentration Maximum (Cmax) of Danirixin in Whole Blood Using Dried Blood Spots
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Assessment method [22]
0
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Blood samples were collected from the participants for the analysis of pharmacokinetic parameter.
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Timepoint [22]
0
0
Days 1 and 168
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Secondary outcome [23]
0
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Time to Reach Maximum Plasma Concentration (Tmax) of Danirixin in Whole Blood Using Dried Blood Spots
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Assessment method [23]
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Blood samples were collected from the participants for the analysis of pharmacokinetic parameter.
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Timepoint [23]
0
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Days 1 and 168
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Eligibility
Key inclusion criteria
Inclusion Criteria
- Participants must be aged between 40 to 80 years of age inclusive, at the time of
signing the informed consent.
- Participants who have COPD (post bronchodilator FEV1/FVC ratio <0.7 and FEV1%
predicted >=40%) based on American Thoracic Society (ATS)/European Respiratory Society
(ERS) current guidelines. Participants with a historical diagnosis of asthma may be
included so long as they have a current diagnosis of COPD.
- History of respiratory symptoms including chronic cough, mucus hypersecretion, and
dyspnea on most days for at least the previous 3 months prior to screening.
- Participants with a documented history of COPD exacerbation(s) in the 12 months prior
to study participation (screening) meeting at least one of the following criteria: >=2
COPD exacerbations resulting in prescription for antibiotics and/or oral
corticosteroids or hospitalization or extended observation in a hospital emergency
room or outpatient center; 1 COPD exacerbation resulting in prescription for
antibiotics and/or oral corticosteroids of hospitalization or extended observation in
a hospital emergency room or outpatient center and a plasma fibrinogen concentration
at screening >=3 grams/liter (300 milligram/deciliter)
- Current and former smokers with a cigarette smoking history of >=10 pack years (1 pack
year = 20 cigarettes smoked per day for 1 year or equivalent). Current smokers are
defined as those who are currently smoking cigarettes (i.e. have smoked at least one
cigarette daily or most days for the month prior to Visit 1). Former smokers are
defined as those who have stopped smoking for at least 6 months prior to Visit 1.
- Participants must have the ability and willingness to use an electronic diary (log
pad) on a daily basis.
- Body weight >=45 kilogram (kg)
- Male or female: A male participant must agree to use contraception during the
treatment period and for at least 60 hours after the last dose of study treatment,
corresponding to approximately 6 half-lives (which is the time needed to eliminate any
teratogenic study treatment) and to refrain from donating sperm during this period; A
female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies: Not a woman of
childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive
guidance during the treatment period and for at least 60 hours after the last dose of
study treatment.
- Capable of giving signed informed consent.
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Minimum age
40
Years
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Maximum age
80
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion Criteria
- Diagnosis of other clinically relevant lung diseases (other than COPD), e.g.
sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis or lung cancer.
- Alpha-1-antitrypsin deficiency as the underlying cause of COPD
- Pulse oximetry <88% at rest at screening. Participants should be tested while
breathing room air. However, participants living at high altitudes (above 5000 feet or
1500 meters above sea level) who are receiving supplemental oxygen can be included
provided they are receiving the equivalent of <4 liter per minute (L/min) and
screening pulse oximetry is measured while on their usual oxygen settings.
- Less than 14 days have elapsed from the completion of a course of antibiotics or oral
corticosteroids for a recent COPD exacerbation.
- A peripheral blood neutrophil count <1.5 x 10^9/L.
- Diagnosis of pneumonia (chest X-ray or CT confirmed) within the 3 months prior to
screening.
- Chest x-ray (posterior-anterior with lateral) or CT scan reveals evidence of a
clinically significant abnormality not believed to be due to the presence of COPD
(historic results up to 1 year prior to screening may be used). For sites in Germany:
If a chest x-ray (or CT scan) within 1 year prior to screening is not available,
approval to conduct a diagnostic chest x-ray will need to be obtained from the Federal
Office of Radiation Protection (BfS).
- History or current evidence of other clinically significant medical condition that is
uncontrolled on permitted therapies. Significant is defined as any disease that, in
the opinion of the Investigator, would put the safety of the participant at risk
through study participation, or that would affect the safety analysis or other
analysis if the disease/condition worsened during the study.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Abnormal and clinically significant 12-lead ECG finding. The investigator will
determine the clinical significance of each abnormal ECG finding in relation to the
participant's medical history and exclude participants who would be at undue risk by
participating in the study. An abnormal and clinically significant finding that would
preclude a participant from entering the study is defined as a 12-lead tracing that is
interpreted as, but not limited to, any of the following: atrial fibrillation with
rapid ventricular rate >120 beats per minute (bpm); sustained or non-sustained
ventricular tachycardia; second degree heart block Mobitz type II and third degree
heart block (unless pacemaker or defibrillator has been implanted); Corrected QT
Interval using Fridericia formula (QTcF) >=500 millisecond (msec) in participants with
QRS <120 msec and QTcF >=530 msec in participants with QRS >=120 msec.
- Previous lung surgery (e.g. lobectomy, pneumonectomy) or lung volume reduction
procedure.
- Current or expected chronic use of macrolide antibiotics during the study period for
the prevention of COPD exacerbations. Examples of chronic use include, but are not
limited to, daily or two to three times per week use for at least 3 months.
- Oral or injectable CYP3A4 or breast cancer resistance protein (BRCP) substrates with a
narrow therapeutic index (CYP3A4 substrates include, but are not limited to,
alfenatil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine,
sirolimus, tacrolimus, and theophylline; BRCP substrates include, but are not limited
to, topotecan.) The Investigator should consult with the Medical Monitor if necessary.
- Current or expected use of phosphodiesterase-4 inhibitors (e.g. roflumilast).
Participants currently receiving roflumilast may be included if they are able to
discontinue use from 30 days prior to screening through the completion of the follow
up visit.
- Participation in a previous clinical trial and has received an investigational product
within any of the following time periods prior to the first dosing day in the current
study: 30 days, 5 half lives, or twice the duration of the biological effect of the
investigational product (whichever is longer).
- Participation in a previous clinical trial with danirixin within 1 year prior to the
first dosing day in the current study
- Exposure to more than four investigational products within 1 year prior to the first
dosing day in the current study.
- Alanine transferase (ALT) >2x upper limit of normal (ULN); bilirubin > 1.5xULN
(isolated bilirubin > 1.5xULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%).
- A positive test for human immunodeficiency virus (HIV) antibody
- A positive pre-study hepatitis B surface antigen or positive hepatitis C antibody
result within 3 months prior to screening.
- Pulmonary rehabilitation: Participants who have taken part in the acute phase of a
pulmonary rehabilitation program within 4 weeks prior to screening or participants who
plan to enter the acute phase of a pulmonary rehabilitation program during the study.
Participants who are in the maintenance phase of a pulmonary rehabilitation program
are not excluded.
- A history of allergy or hypersensitivity to any of the ingredients in the study
treatment.
- A known or suspected history of alcohol or drug abuse within the 2 years prior to
screening.
- Inability to read: in the opinion of the Investigator, any participant who is unable
to read and/or would not be able to complete study related materials.
- Affiliation with the study site: study investigators, sub-investigators, study
coordinators, employees of a study investigator, sub-investigator or study site, or
immediate family member of any of the above that are involved with the study.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
25/04/2017
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
5/10/2018
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Sample size
Target
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Accrual to date
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Final
614
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
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GSK Investigational Site - Randwick
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Recruitment hospital [2]
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GSK Investigational Site - Westmead
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Recruitment hospital [3]
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GSK Investigational Site - Clayton
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Recruitment hospital [4]
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GSK Investigational Site - Footscray
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Recruitment hospital [5]
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GSK Investigational Site - Murdoch
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Recruitment postcode(s) [1]
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2031 - Randwick
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Recruitment postcode(s) [2]
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2145 - Westmead
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Recruitment postcode(s) [3]
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3168 - Clayton
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Recruitment postcode(s) [4]
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3011 - Footscray
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Recruitment postcode(s) [5]
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6150 - Murdoch
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Recruitment outside Australia
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United States of America
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Alabama
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United States of America
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Kansas
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Missouri
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North Carolina
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Oregon
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United States of America
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South Carolina
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United States of America
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West Virginia
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Canada
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Manitoba
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Rheinland-Pfalz
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Germany
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Sachsen
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Germany
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Schleswig-Holstein
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Germany
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Berlin
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Korea, Republic of
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Bucheon-Si, Gyeonggi-Do
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Korea, Republic of
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Wonju-si, Gangwon-do
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Netherlands
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Alkmaar
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Netherlands
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Breda
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Netherlands
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Eindhoven
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Netherlands
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Hengelo
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Netherlands
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Hoorn
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Poland
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Ksawerow
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Poland
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Lubin
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Poland
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Ostrowiec Swietokrzyski
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Poland
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Szczecin
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Poland
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Wroclaw
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Romania
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Bacau
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Romania
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Bucharest
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Romania
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Cluj Napoca
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Romania
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Constanta
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Romania
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Focsani
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Romania
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Iasi
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Romania
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Ramnicu Valcea
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Romania
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State/province [39]
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Slobozia
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Romania
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Suceava
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Pozuelo De Alarcón/Madrid
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Spain
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Salamanca
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Spain
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Santander
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Spain
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State/province [46]
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Zaragoza
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
GlaxoSmithKline
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
Danirixin (DNX) is a selective CXC chemokine receptor (CXCR2) antagonist being developed as a
potential anti-inflammatory agent for the treatment of COPD. This is a Phase 2, randomized,
double-blind (Sponsor Open) study. The primary objective of the study is to evaluate the
clinical activity and safety of danirixin compared with placebo in participants with COPD.
Following baseline assessments collected over a 7 day period participants will be randomized
(1:1:1:1:1:1) to receive one of five dose strengths of danirixin (5 milligram [mg], 10 mg, 25
mg, 35 mg and 50 mg) or placebo. Study treatment will be administered orally twice daily for
24 weeks. Participants will continue with their standard of care inhaled medications (i.e.
long acting bronchodilators with or without inhaled corticosteroids) while receiving study
treatment. Follow up will continue up to 28 days post last dose. Approximately 700
participants will be screened with a target of 540 participants completing 24 weeks of
treatment and key study assessments.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT03034967
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Trial related presentations / publications
Lazaar AL, Miller BE, Donald AC, Keeley T, Ambery C, Russell J, Watz H, Tal-Singer R; for 205724 Investigators. CXCR2 antagonist for patients with chronic obstructive pulmonary disease with chronic mucus hypersecretion: a phase 2b trial. Respir Res. 2020 Jun 12;21(1):149. doi: 10.1186/s12931-020-01401-4.
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Public notes
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Contacts
Principal investigator
Name
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GSK Clinical Trials
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Address
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GlaxoSmithKline
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Phone
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Fax
0
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Email
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Contact person for public queries
Name
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Address
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03034967
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