A Phase 2 interventional study of Danirixin and Placebo in Pulmonary Disease, Chronic Obstructive, sponsored by GlaxoSmithKline. Terminated at 1 site in United Kingdom. Open to participants aged 50 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-03-29.
Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment
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Among 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline — 7 open to participants now, 8 under way, 5 of them phase 3. Pulmonary Disease, Chronic Obstructive · GlaxoSmithKline.
Among the 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline, this one is the 205th largest by enrollment of the 236 interventional ones that give a count, is one of 18 that started in 2017, is one of 46 in phase 2, and was the 238th registered.
5,522 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 857 are open to participants now.
Browse Pulmonary Disease, Chronic Obstructive studies →7 of the 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline are open now, in 12 countries. Recruiting first, the newest first:
GlaxoSmithKline · Sites in United States, Argentina
Ages 40–80
GlaxoSmithKline · Sites in United States, Japan
Ages 40–80
GlaxoSmithKline · Sites in United Kingdom
Ages 18–55 · Healthy volunteers
GlaxoSmithKline · Sites in United States, Australia, Bulgaria and 10 more countries
Ages 40–75
GlaxoSmithKline · Sites in United States, Argentina, Australia and 13 more countries
Ages 40–80
By country, each count listing its studies:
Of the 557 Pulmonary Disease, Chronic Obstructive studies recruiting now, 306 (55%) set no upper age limit and 82 (15%) stop at 75 or younger; 29 take children under 18; 89 take healthy volunteers.
This study: 50 Years to 75 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
276 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 84 · Phase 2 47 · Phase 3 65 · Phase 4 38
First in 2000; this study’s year is marked. 18 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 19 is below the median of 62 across 3,840 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.
Median enrollment 101 across the 236 interventional studies, 1,248 across the 40 observational. Of the 264 that completed or were terminated, 141 (53%) have results posted.
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GlaxoSmithKline is the lead sponsor of 3,650 studies on the registry; 117 are open to participants now.
Of its 265 completed or terminated interventional studies of FDA-regulated products, 241 (91%) have results posted.
2 of the studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06154837GlaxoSmithKlineA Study for GSK3862995B in Healthy Participants and Participants With Chronic Obstructive Pulmonary Disease | 2026-12-16 |
| NCT07789899GlaxoSmithKlineA Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Two GSK3862995B Formulations in Healthy Participants | 2027-09-07 |
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Among the 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline, from their registry updates:
This tab as a report to print or save as PDF → With an account.
The inflammation associated with COPD is characterized by a prominent infiltration of neutrophils in lung tissue and airways. The CXC chemokine receptor type 2 (CXCR2) plays a pivotal role in neutrophil recruitment to the lungs resulting in progressive fibrosis, airway stenosis, and destruction of the lung parenchyma characteristic of COPD. There is a paucity of novel therapies that target these symptoms, and there are no currently available therapies that modify disease progression in COPD. Danirixin (GSK1325756) is a selective CXCR2 antagonist being developed as a potential anti-inflammatory agent for the treatment of COPD and influenza. This study is a mechanistic study which aims to evaluate the effect of danirixin in reducing neutrophil extracellular traps (NETs) formation (or NETosis). Subjects will be randomized (3:1) to receive danirixin hydrobromide (HBr) 35 milligram (mg) orally twice daily or matching placebo for 14 days. Subjects may continue to use rescue medication(s) and inhaled COPD maintenance medication(s) during the study. The study will consist of a screening period of up to 30 days, a 2 week treatment period, and a 1-week follow-up visit via phone call. Approximately 50 subjects will be screened to obtain approximately 24 subjects to complete the study.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Eligible subjects will receive danirixin 35 mg tablet with food twice daily for 14 Days.
Drug: Danirixin · Drug: Rescue medication · Drug: Inhaled COPD maintenance medication
Eligible subjects will receive placebo tablet with food twice daily for 14 Days.
Drug: Placebo · Drug: Rescue medication · Drug: Inhaled COPD maintenance medication
Danirixin will be available as 35 mg oval shaped, white film coated HBr embossed tablets.
Placebo will be available as oval shaped, white film coated tablets.
Subjects may continue to use rescue medication(s) anytime during the study. The following rescue medications may be used: short acting beta agonists, short acting muscarinic antagonists, or short acting combination bronchodilators.
Subjects may continue to use inhaled COPD maintenance medication(s) during the study, at the discretion of the GSK Medical Monitor and/or Investigator. The following maintenance medications may be used: long acting bronchodilator medications (e.g. long-acting muscarinic antagonist \[LAMA\], long-acting beta-agonist \[LABA\]) and long-acting bronchodilator combination therapies (e.g. LAMA/LABA) and long-acting bronchodilator/inhaled corticosteroid steroid combination (ICS) therapies (e.g. LABA/ICS, LAMA/LABA/ICS)
Percentage Change From Baseline in Sputum Neutrophil Extracellular Traps (NETs) Quantified by Histone-Elastase Complexes
Sputum samples were collected at indicated time points to assess NET formation via histone elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value. Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by 100. Analysis was performed using a mixed effect repeated measures model with covariates of treatment group, log(Baseline NETs) and treatment group by day interaction. The response variable was the log of the ratio of post-Baseline NETs to Baseline NETs. Primary completer population consisted of all participants in the Modified Intent-To-Treat population who had completed the assessments supporting the primary endpoint (sputum NETs).
Time frame: Baseline (Day 1), Day 7 and Day 14
Change From Baseline in Sputum NETs Quantified by Deoxyribonucleic Acid (DNA)-Elastase Complexes
Sputum samples were collected at indicated time points to assess NET formation via DNA elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1), Day 7 and Day 14
Change From Baseline in Percentage of Microscope Field Area Occupied by Sputum NETs
Sputum samples were collected at indicated time points and NETs area was quantified by microscopy. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1), Day 7 and Day 14
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes, Modified Intent-to-Treat Population consisted of all randomized participants who received at least one dose of study treatment.
Time frame: Up to Day 21
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1), Day 7 and Day 14
Change From Baseline in Heart Rate
Heart rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1), Day 7 and Day 14
Change From Baseline in Respiration Rate
Respiration rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1), Day 7 and Day 14
Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)
Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Spirometry: Forced Expiratory Volume in One Second (FEV1) at Indicated Time Points
FEV1 is the amount of air that can be forcefully exhaled from the lungs in the first second of a forced exhalation. It was measured by spirometry test. Mean and standard deviation data of FEV1 measured at Day 1 and Day 14 have been presented.
Time frame: Day 1 and Day 14
Spirometry: Forced Vital Capacity (FVC) at Indicated Time Points
FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Mean and standard deviation data of FVC measured at Day 1 and Day 14 have been presented.
Time frame: Day 1 and Day 14
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets Counts, Total Neutrophils, White Blood Cell (WBC) Count
Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils and WBC count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume
Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Volume. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin
Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Hematology Parameter: Red Blood Cell Count
Blood samples were collected to analyze the hematology parameter: Red Blood Cell count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, Urea
Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Chemistry Parameters: Creatinine, Direct Bilirubin, Total Bilirubin
Blood samples were collected to analyze the chemistry parameters: Creatinine, Direct Bilirubin and Total Bilirubin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Urinalysis Parameter: Specific Gravity
Urinary specific gravity measurement is a part of routine urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)
Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Sputum Resistin Levels
Sputum samples were collected at indicated time points to analyze resistin levels. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1), Day 7 and Day 14
Change From Baseline in the Ratio of Sputum NETs to Sputum Neutrophils
Sputum samples were collected to calculate ratio of sputum NETs to sputum neutrophils. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value. The ratio is calculated as the sputum NETs divided by the number of sputum neutrophils.
Time frame: Baseline (Day 1) and Day 14
Change From Baseline in Sputum Elastase Activity
Sputum samples were collected at indicated time points to analyze sputum elastase activity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1), Day 7 and Day 14
Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by DNA Release
Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by DNA release. DNA-elastase complexes quantified NETs formation. Phorbol 12-myristate 13-acetate (PMA) was used to induce inflammation and NETs formation in the PMA stimulated samples. Blood from participants were tested at Baseline and Day 14 for non-PMA stimulated samples, and at Baseline and Day 14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally (non PMA induced) or where NETs formation was already raised (PMA stimulated). Hence participants were counted in both the categories - PMA stimulated and not PMA stimulated. NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
Time frame: Baseline (Day 1) and Day 14
Percentage Change From Baseline in Peripheral Blood Neutrophil NETs Formation Quantified by Microscopy
Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by microscopy.DNA-elastase complexes quantified NETs formation.PMA was used to induce inflammation and NETs formation in PMA stimulated samples. Blood from participants were tested at Baseline and Day14 for non-PMA stimulated samples,and at Baseline and Day14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally(non PMA induced)or where NETs formation was already raised(PMA stimulated).Participants were counted in both categories-PMA stimulated and not PMA stimulated.NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA.Baseline was considered as Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by100.
Time frame: Baseline (Day 1) and Day 14
Maximum Observed Concentration (Cmax) of Danirixin
Blood samples were collected to evaluate the pharmacokinetic (PK) of danirixin at the indicated time points for the analysis of Cmax. PK population consisted of all participants in the Modified Intent-To-Treat population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values).
Time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
Time to Cmax (Tmax) of Danirixin
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax.
Time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
Area Under the Blood Concentration-time Curve [AUC(0-t)] of Danirixin
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t).
Time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
Time of Last Observed Concentration (Tlast) of Danirixin
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast.
Time frame: Days 1 and 14: Pre-dose and 0.5, 1, 2 and 4 hours post-dose
The study was conducted at single center in United Kingdom. This study was terminated early due to a change in the benefit risk profile of danirixin observed in another study NCT03034967, leading to cessation of the overall danirixin development program.
| Milestone | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Started | 5 | 14 |
| Completed | 5 | 14 |
| Not completed | 0 | 0 |
Sputum samples were collected at indicated time points to assess NET formation via histone elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value. Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by 100. Analysis was performed using a mixed effect repeated measures model with covariates of treatment group, log(Baseline NETs) and treatment group by day interaction. The response variable was the log of the ratio of post-Baseline NETs to Baseline NETs. Primary completer population consisted of all participants in the Modified Intent-To-Treat population who had completed the assessments supporting the primary endpoint (sputum NETs).
| Percent change | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 7, n=3,6 | -3.2 (-77.0 to 306.6) | -9.4 (-64.4 to 130.6) |
| Day 14, n=3,8 | -30.5 (-71.7 to 70.7) | -13.6 (-49.1 to 46.5) |
Sputum samples were collected at indicated time points to assess NET formation via DNA elastase complexes. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Units per milliliter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 7, n=3,6 | 1.83 ± 4.610 | 0.63 ± 1.859 |
| Day 14, n=3,8 | -4.53 ± 2.696 | 2.08 ± 4.072 |
Sputum samples were collected at indicated time points and NETs area was quantified by microscopy. Baseline was considered as Day 1. If Day 1 values were missing, screening value was imputed for Baseline. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Percentage of microscope field area | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 7 | NA ± NA | NA ± NA |
| Day 14 | 0.900 ± 0.9200 | -0.259 ± 0.5183 |
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment such as important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes, Modified Intent-to-Treat Population consisted of all randomized participants who received at least one dose of study treatment.
| Participants | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| AEs | 3 | 6 |
| SAEs | 0 | 0 |
SBP and DBP were measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Millimeters of mercury | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| SBP, Day 7 | -11.2 ± 17.01 | -4.1 ± 17.70 |
| SBP, Day 14 | -1.4 ± 16.10 | -5.3 ± 15.77 |
| DBP, Day 7 | -2.2 ± 9.91 | -2.1 ± 10.34 |
| DBP, Day 14 | 2.6 ± 11.01 | -5.3 ± 7.98 |
Heart rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Beats per minute | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 7 | 6.8 ± 6.02 | 1.6 ± 11.28 |
| Day 14 | 4.0 ± 6.89 | 0.1 ± 6.86 |
Respiration rate was measured in seated position after 5 minutes rest for the participants at indicated time points. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Breaths per minute | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 7 | -0.6 ± 1.95 | 1.8 ± 2.67 |
| Day 14 | 0.2 ± 0.84 | 2.1 ± 3.43 |
Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Milliseconds | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| PR Interval | 7.6 ± 20.44 | -4.8 ± 15.69 |
| QRS Duration | -0.3 ± 1.12 | 0.5 ± 5.55 |
| QT Interval | -4.8 ± 10.05 | 3.7 ± 15.67 |
| QTcF Interval | -4.6 ± 0.38 | -1.6 ± 5.96 |
FEV1 is the amount of air that can be forcefully exhaled from the lungs in the first second of a forced exhalation. It was measured by spirometry test. Mean and standard deviation data of FEV1 measured at Day 1 and Day 14 have been presented.
| Liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 1 | 2.458 ± 0.6331 | 1.914 ± 0.7267 |
| Day 14 | 2.344 ± 0.7174 | 1.910 ± 0.7428 |
FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It was measured by spirometry test. Mean and standard deviation data of FVC measured at Day 1 and Day 14 have been presented.
| Liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 1 | 4.026 ± 1.2021 | 3.416 ± 1.1304 |
| Day 14 | 4.036 ± 1.3992 | 3.369 ± 1.1456 |
Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets counts, Total neutrophils and WBC count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Giga cells per liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Basophils | 0.00 ± 0.000 | -0.02 ± 0.058 |
| Eosinophils | 0.040 ± 0.0686 | -0.020 ± 0.0609 |
| Lymphocytes | -0.20 ± 0.316 | -0.08 ± 0.269 |
| Monocytes | -0.04 ± 0.114 | 0.02 ± 0.080 |
| Platelets counts | 8.2 ± 18.94 | -7.9 ± 41.66 |
| Total neutrophils | -0.38 ± 0.965 | 0.29 ± 0.943 |
| WBC count | -0.56 ± 0.948 | 0.16 ± 1.075 |
Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Percentage of red blood cells in blood | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in Hematology Parameter: Hematocrit | -0.0058 ± 0.02279 | -0.0115 ± 0.02085 |
Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Grams per liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in Hematology Parameter: Hemoglobin | -2.2 ± 6.72 | -5.4 ± 7.99 |
Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Volume. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Femtoliter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 0.06 ± 1.339 | 0.31 ± 1.263 |
Blood samples were collected to analyze the hematology parameter: Mean Corpuscular Hemoglobin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Picograms | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | -0.08 ± 0.920 | -0.22 ± 0.749 |
Blood samples were collected to analyze the hematology parameter: Red Blood Cell count. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Trillion cells per liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in Hematology Parameter: Red Blood Cell Count | -0.070 ± 0.2081 | -0.154 ± 0.2171 |
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| International units per liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| ALT | -1.6 ± 4.39 | -1.9 ± 8.24 |
| ALP | 2.8 ± 6.26 | 1.3 ± 13.89 |
| AST | -0.6 ± 2.61 | -3.1 ± 2.11 |
Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Millimoles per liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Calcium | -0.032 ± 0.0782 | -0.034 ± 0.0947 |
| Glucose | 0.36 ± 0.635 | 0.12 ± 0.398 |
| Potassium | -0.12 ± 0.148 | 0.06 ± 0.287 |
| Sodium | 0.0 ± 1.58 | 0.2 ± 2.04 |
| Urea | -0.42 ± 0.867 | 0.26 ± 0.777 |
Blood samples were collected to analyze the chemistry parameters: Creatinine, Direct Bilirubin and Total Bilirubin. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Micromoles per liter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Creatinine | 2.6 ± 5.86 | 1.2 ± 6.99 |
| Direct Bilirubin | -0.4 ± 0.55 | 0.7 ± 1.65 |
| Total Bilirubin | 0.8 ± 0.84 | -1.2 ± 3.26 |
Urinary specific gravity measurement is a part of routine urinalysis. Urine specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. Urine samples were collected from participants at indicated time points for analysis of specific gravity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Unitless | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in Urinalysis Parameter: Specific Gravity | 0.0030 ± 0.00908 | 0.0046 ± 0.00887 |
Urine samples were collected from participants at indicated time points for analysis of pH. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| pH | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) | 1.00 ± 1.225 | -0.25 ± 0.672 |
Sputum samples were collected at indicated time points to analyze resistin levels. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Nanograms per milliliter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 7, n=3,6 | 8.93 ± 15.513 | -2.01 ± 4.629 |
| Day 14, n=3,8 | 15.28 ± 27.619 | 2.61 ± 2.711 |
Sputum samples were collected to calculate ratio of sputum NETs to sputum neutrophils. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value. The ratio is calculated as the sputum NETs divided by the number of sputum neutrophils.
| Ratio | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Change From Baseline in the Ratio of Sputum NETs to Sputum Neutrophils | 0.5200 ± 0.41000 | 0.4557 ± 0.53149 |
Sputum samples were collected at indicated time points to analyze sputum elastase activity. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Nanograms per milliliter | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Day 7, n=3,6 | 638.0 ± 381.36 | 238.0 ± 224.50 |
| Day 14, n=3,8 | 411.3 ± 439.20 | 66.1 ± 45.64 |
Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by DNA release. DNA-elastase complexes quantified NETs formation. Phorbol 12-myristate 13-acetate (PMA) was used to induce inflammation and NETs formation in the PMA stimulated samples. Blood from participants were tested at Baseline and Day 14 for non-PMA stimulated samples, and at Baseline and Day 14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally (non PMA induced) or where NETs formation was already raised (PMA stimulated). Hence participants were counted in both the categories - PMA stimulated and not PMA stimulated. NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA. Baseline was considered as Day 1. Change from Baseline was calculated as post-Baseline value minus Baseline value.
| Relative fluorescence units | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Not PMA stimulated | 3044.8 ± 4251.78 | -721.1 ± 731.82 |
| PMA stimulated | -96.8 ± 9418.43 | -1211.0 ± 5102.21 |
Blood samples were collected at indicated time points to analyze peripheral blood neutrophil NETs formation by microscopy.DNA-elastase complexes quantified NETs formation.PMA was used to induce inflammation and NETs formation in PMA stimulated samples. Blood from participants were tested at Baseline and Day14 for non-PMA stimulated samples,and at Baseline and Day14 in PMA-stimulated samples to test whether treatment had any effect on NETs formation either naturally(non PMA induced)or where NETs formation was already raised(PMA stimulated).Participants were counted in both categories-PMA stimulated and not PMA stimulated.NETs formation in peripheral blood was measured with SYTOX green fluorescence quantification of extracellular DNA.Baseline was considered as Day1.Change from Baseline was calculated as post-Baseline value minus Baseline value.Percentage change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplied by100.
| Percent change | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| Not PMA stimulated | 927.5 ± 585.03 | 560.5 ± 395.72 |
| PMA stimulated | 44.7 ± 41.79 | 90.6 ± 60.33 |
Blood samples were collected to evaluate the pharmacokinetic (PK) of danirixin at the indicated time points for the analysis of Cmax. PK population consisted of all participants in the Modified Intent-To-Treat population who had at least 1 non-missing PK assessment (non-quantifiable values were considered as non-missing values).
| Nanograms per milliliter | Danirixin Hydrobromide 35 mg |
|---|---|
| Day 1, n=14 | 855.2 ± 52.29 |
| Day 14, n=13 | 1135.2 ± 65.73 |
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tmax.
| Hours | Danirixin Hydrobromide 35 mg |
|---|---|
| Day 1, n=14 | 1.000 (0.50 to 4.00) |
| Day 14, n=13 | 1.000 (0.50 to 4.00) |
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of AUC(0-t).
| Hours * nanograms per milliliter | Danirixin Hydrobromide 35 mg |
|---|---|
| Day 1 | 2173.4 ± 39.57 |
| Day 14 | 2751.1 ± 51.24 |
Blood samples were collected to evaluate the PK of danirixin at the indicated time points for the analysis of Tlast.
| Hours | Danirixin Hydrobromide 35 mg |
|---|---|
| Day 1, n=14 | 4.000 (4.00 to 4.05) |
| Day 14, n=13 | 4.000 (4.00 to 4.00) |
Collected over AEs and SAEs were collected from start of the treatment up to Day 21. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/5 (0%) | 0/5 (0%) | 3/5 (60%) |
| Danirixin Hydrobromide 35 mg | 0/14 (0%) | 0/14 (0%) | 6/14 (42.9%) |
| Event | Placebo | Danirixin Hydrobromide 35 mg |
|---|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 1/5 | 1/14 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 1/5 | 1/14 |
| Sputum increasedRespiratory, thoracic and mediastinal disorders | 1/5 | 0/14 |
| Dry mouthGastrointestinal disorders | 1/5 | 0/14 |
| MalaiseGeneral disorders | 1/5 | 0/14 |
| Back painMusculoskeletal and connective tissue disorders | 1/5 | 0/14 |
| MyalgiaMusculoskeletal and connective tissue disorders | 1/5 | 0/14 |
| DysgeusiaNervous system disorders | 1/5 | 0/14 |
| Night sweatsSkin and subcutaneous tissue disorders | 1/5 | 0/14 |
| Decreased appetiteMetabolism and nutrition disorders | 1/5 | 0/14 |
| Age, Continuous(Years) | Placebo | Danirixin Hydrobromide 35 mg | Total |
|---|---|---|---|
| Mean | 61.6 ± 6.02 | 65.3 ± 7.03 | 64.3 ± 6.82 |
| Sex: Female, Male(Participants) | Placebo | Danirixin Hydrobromide 35 mg | Total |
|---|---|---|---|
| Female | 2 | 6 | 8 |
| Male | 3 | 8 | 11 |
| Race/Ethnicity, Customized(Participants) | Placebo | Danirixin Hydrobromide 35 mg | Total |
|---|---|---|---|
| White: White/Caucasian/European Heritage | 5 | 14 | 19 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD for this study is available via the Clinical Study Data Request site.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Data sharing details ↗ · clinicalstudydatarequest.com
Ran from Nov 2017 to primary completion in Oct 2018, 10 months.
Results were first posted in Nov 2019, 1 year 1 month after primary completion.
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Studies of the drug tested here: Danirixin
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