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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03034967




Registration number
NCT03034967
Ethics application status
Date submitted
25/01/2017
Date registered
27/01/2017

Titles & IDs
Public title
Danirixin Dose Ranging Study in Participants With Chronic Obstructive Pulmonary Disease (COPD)
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)
Secondary ID [1] 0 0
2016-003675-21
Secondary ID [2] 0 0
205724
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Respiratory Symptoms Measured by Evaluating Respiratory Symptoms (E-RS) in COPD. E-RS: COPD Total Score
Timepoint [1] 0 0
Baseline and Month 6
Primary outcome [2] 0 0
Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Breathlessness Score)
Timepoint [2] 0 0
Baseline and Month 6
Primary outcome [3] 0 0
Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Cough and Sputum Score)
Timepoint [3] 0 0
Baseline and Month 6
Primary outcome [4] 0 0
Change From Baseline in Respiratory Symptoms Measured by E-RS in COPD (E-RS: COPD Chest Symptoms Score)
Timepoint [4] 0 0
Baseline and Month 6
Primary outcome [5] 0 0
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Timepoint [5] 0 0
Up to Day 196
Primary outcome [6] 0 0
Number of Participants With Worst Case Hematology Parameter Results by Potential Clinical Importance (PCI)
Timepoint [6] 0 0
Up to Day 196
Primary outcome [7] 0 0
Number of Participants With Worst Case Clinical Chemistry Parameter Results by PCI
Timepoint [7] 0 0
Up to Day 196
Primary outcome [8] 0 0
Number of Participants With Worst Case Vital Signs Parameter Results by PCI
Timepoint [8] 0 0
Up to Day 168
Primary outcome [9] 0 0
Number of Participants With Worst Case Post-Baseline Abnormal 12-lead Electrocardiogram (ECG) Findings
Timepoint [9] 0 0
Baseline and Day 168
Secondary outcome [1] 0 0
Number of Moderate or Severe Healthcare Resource Utilization (HCRU) Exacerbations Per Participant
Timepoint [1] 0 0
Up to Day 196
Secondary outcome [2] 0 0
Number of Responders E-RS in COPD (E-RS): COPD Total Score
Timepoint [2] 0 0
Month 6
Secondary outcome [3] 0 0
Number of EXACT Events Per Participant
Timepoint [3] 0 0
Up to Day 196
Secondary outcome [4] 0 0
Time to First EXACT Event
Timepoint [4] 0 0
Up to Day 168
Secondary outcome [5] 0 0
Severity of EXACT Event
Timepoint [5] 0 0
Up to Day 168
Secondary outcome [6] 0 0
EXACT Event Duration for All Events
Timepoint [6] 0 0
Up to Day 168
Secondary outcome [7] 0 0
Time to First HCRU-defined COPD Exacerbation
Timepoint [7] 0 0
Up to Day 196
Secondary outcome [8] 0 0
Time to First Severe HCRU-defined COPD Exacerbation
Timepoint [8] 0 0
Up to Day 196
Secondary outcome [9] 0 0
HCRU-defined Exacerbation Duration
Timepoint [9] 0 0
Up to Day 196
Secondary outcome [10] 0 0
Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score
Timepoint [10] 0 0
Baseline, Days 84 and 168
Secondary outcome [11] 0 0
Number of SGRQ Responder
Timepoint [11] 0 0
Day 84 and Day 168
Secondary outcome [12] 0 0
Change From Baseline COPD Assessment Test (CAT) Total Score
Timepoint [12] 0 0
Baseline, Days 84 and 168
Secondary outcome [13] 0 0
Number of CAT Responder
Timepoint [13] 0 0
Day 84 and Day 168
Secondary outcome [14] 0 0
Change From Baseline in Post-bronchodilator FEV1 as a Lung Function Assessment
Timepoint [14] 0 0
Baseline, Days 84 and 168
Secondary outcome [15] 0 0
Percent Predicted Normal FEV1
Timepoint [15] 0 0
At Screening
Secondary outcome [16] 0 0
Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC) as a Lung Function Assessment
Timepoint [16] 0 0
Baseline, Days 84 and 168
Secondary outcome [17] 0 0
Change From Baseline in Post-bronchodilator FEV1/FVC Ratio as a Lung Function Assessment
Timepoint [17] 0 0
Baseline, Days 84 and 168
Secondary outcome [18] 0 0
Change From Baseline Number of Puffs of Rescue Medication Per Day
Timepoint [18] 0 0
Baseline, Months 1, 2, 3, 4, 5 and 6
Secondary outcome [19] 0 0
Participant Experience of Physical Activity Measured Using PROactive Physical Activity in COPD (C-PPAC) Questionnaire
Timepoint [19] 0 0
Days 84 and 168
Secondary outcome [20] 0 0
Danirixin Whole Blood Pharmacokinetic Concentration-Time Data
Timepoint [20] 0 0
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
Secondary outcome [21] 0 0
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
Timepoint [21] 0 0
Days 1 and 168
Secondary outcome [22] 0 0
Concentration Maximum (Cmax) of Danirixin in Whole Blood Using Dried Blood Spots
Timepoint [22] 0 0
Days 1 and 168
Secondary outcome [23] 0 0
Time to Reach Maximum Plasma Concentration (Tmax) of Danirixin in Whole Blood Using Dried Blood Spots
Timepoint [23] 0 0
Days 1 and 168

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.
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/10/2018
Sample size
Target
Accrual to date
Final
614
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [2] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [3] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [4] 0 0
GSK Investigational Site - Footscray
Recruitment hospital [5] 0 0
GSK Investigational Site - Murdoch
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3011 - Footscray
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Kansas
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
West Virginia
Country [8] 0 0
Canada
State/province [8] 0 0
Manitoba
Country [9] 0 0
Canada
State/province [9] 0 0
Nova Scotia
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Germany
State/province [12] 0 0
Hessen
Country [13] 0 0
Germany
State/province [13] 0 0
Niedersachsen
Country [14] 0 0
Germany
State/province [14] 0 0
Rheinland-Pfalz
Country [15] 0 0
Germany
State/province [15] 0 0
Sachsen
Country [16] 0 0
Germany
State/province [16] 0 0
Schleswig-Holstein
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Bucheon-Si, Gyeonggi-Do
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Incheon
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Wonju-si, Gangwon-do
Country [22] 0 0
Netherlands
State/province [22] 0 0
Alkmaar
Country [23] 0 0
Netherlands
State/province [23] 0 0
Breda
Country [24] 0 0
Netherlands
State/province [24] 0 0
Eindhoven
Country [25] 0 0
Netherlands
State/province [25] 0 0
Hengelo
Country [26] 0 0
Netherlands
State/province [26] 0 0
Hoorn
Country [27] 0 0
Poland
State/province [27] 0 0
Ksawerow
Country [28] 0 0
Poland
State/province [28] 0 0
Lubin
Country [29] 0 0
Poland
State/province [29] 0 0
Ostrowiec Swietokrzyski
Country [30] 0 0
Poland
State/province [30] 0 0
Szczecin
Country [31] 0 0
Poland
State/province [31] 0 0
Wroclaw
Country [32] 0 0
Romania
State/province [32] 0 0
Bacau
Country [33] 0 0
Romania
State/province [33] 0 0
Bucharest
Country [34] 0 0
Romania
State/province [34] 0 0
Cluj Napoca
Country [35] 0 0
Romania
State/province [35] 0 0
Constanta
Country [36] 0 0
Romania
State/province [36] 0 0
Focsani
Country [37] 0 0
Romania
State/province [37] 0 0
Iasi
Country [38] 0 0
Romania
State/province [38] 0 0
Ramnicu Valcea
Country [39] 0 0
Romania
State/province [39] 0 0
Slobozia
Country [40] 0 0
Romania
State/province [40] 0 0
Suceava
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Pozuelo De Alarcón/Madrid
Country [44] 0 0
Spain
State/province [44] 0 0
Salamanca
Country [45] 0 0
Spain
State/province [45] 0 0
Santander
Country [46] 0 0
Spain
State/province [46] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study is available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com/Posting.aspx?ID=20593


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03034967