Pulmonary Disease, Chronic ObstructivePhase 1NCT03457727

GSK1325756 Relative Bioavailability Study in Healthy Elderly Subjects

A Phase 1 study testing Danirixin and Omeprazole in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 65 to 80 yearsHealthy volunteers can take part
Conditions the study is for: Pulmonary Disease, Chronic Obstructive
What is being tested?: Danirixin and Omeprazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteUnited States
Study dates: 7 Mar 2018to 25 Jul 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 65 to 80 years
All sexes
Healthy volunteers accepted
Older adult

Who may be able to join

Subjects must be 65 to 80 years of age inclusive, at the Screening Visit.
Subjects who are healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring or a subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives. Additionally, laboratory assessments that are specifically listed in the inclusion or exclusion criteria and are outside of the reference range can be repeated once during the screening period.
Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 34 kg per meter square (kg/m^2) (inclusive).
Male or female subjects will be included. A female subject 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.
AST, ALT, alkaline phosphatase and bilirubin <= 1.5 × upper limit of normal (ULN) (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35 percent).
Resting BP of <= 160/90 millimeters of mercury (mmHg), irrespective of anti-hypertensive medication status for the subject.
Able to consume the Food and Drug Administration (FDA) defined high fat meal within 30 minutes in each of the four treatment periods where study treatment is administered in a fed state.

Who cannot join

Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test [TST; defined as a skin induration <5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history] or a positive (not indeterminate) QuantiFERON®-TB Gold test.
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
ALT >1.5x ULN
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).

Show all 25Show fewer

Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Corrected QT interval (QTc) >450 milliseconds (msec).
Use of prescription or non-prescription drugs, including proton pump inhibitors, histamine receptor 2 antagonists, systemic antacid medications (unless these can be held during the study), vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment until completion of the last study assessment , unless in the opinion of the investigator and GSK Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety. Some examples of exceptions (permitted medications) are: Stable dose of anti-hypertensive medication for at least 3 months prior to the screening visit; Stable dose of lipid-lowering medications (statins or fibrates) for at least 3 months prior to the screening visit; Antacids up to 24 hours prior to dosing.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Participation in a previous clinical trial with danirixin within 1 year prior to the first dosing day in the current study.
Female Subjects: Positive urine beta-human chorionic gonadotropin (beta-hCG) test at screening.
Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
For potent immunosuppressive agents, presence of the Hepatitis B core antibody (HBcAb) should also lead to exclusion from the study even if HBsAg is negative.
Positive pre-study drug/alcohol screen.
Positive human immunodeficiency virus (HIV) antibody test.
Regular use of known drugs of abuse.
Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study treatment until collection of the final blood sample.
Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 90 days prior to screening.
Sensitivity to heparin or heparin-induced thrombocytopenia.
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

GSK Investigational Site
Overland Park, Kansas, 66211

Other trials in United States

About this study

Official title: A Two Part, Randomized, Open-label, Cross Over Study in Healthy Elderly Participants to Evaluate the Relative Bioavailability of Hydrobromide Salt Tablet Formulations of Danirixin in the Fed and Fasted States, and to Evaluate the Effect of Food and Gastric Acid Secretion Suppression on Danirixin Pharmacokinetics Following Administration of Hydrobromide Salt Tablets

This 2-part study will be carried out on healthy elderly subjects to evaluate relative bioavailability of danirixin formulations. Part A will support the selection of the formulation and Part B will assess food effect, bioavailability and pharmacokinetic (PK) profile of selected formulation from Part A. Danirixin is currently administered with food, therefore the investigation of food effect for the selected formulation could potentially enable dosing without food. Approximately 16 subjects will be included in Part A and approximately 24 subjects will be included in Part B. Both parts will include a screening phase, treatment phase with in-between washout period and a follow-up phase.

Conditions: Pulmonary Disease, Chronic Obstructive
Being tested: Danirixin, Omeprazole
Keywords: Danirixin, Healthy, Food effect, Relative Bioavailability, Hydrobromide Salt
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DanirixinDrug
Danirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.
OmeprazoleDrug
Omeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects.

Study groups in NCT03457727
Study group	Role	What they receive
Subjects receiving danirixin: Part A	Experimental	Subjects will receive a single oral dose of 50 mg danirixin reference and test formulations with food and 240 mL of water in a cross-over manner. Receives: Drug: Danirixin
Subjects receiving danirixin without omeprazole: Part B	Experimental	Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) in fasted or fed state in a cross-over manner. Receives: Drug: Danirixin
Subjects receiving danirixin with omeprazole: Part B	Experimental	Subjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) along with once daily 40 mg OMP capsule in fasted or fed state in a cross-over manner. Receives: Drug: Danirixin; Drug: Omeprazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the pharmacokinetic (PK) profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Maximum Observed Concentration (Cmax) of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Number of Participants With Any Adverse Event (AE) and Serious Adverse Events (SAEs) in Part 1
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Measured: Up to 29 days in Part 1
Number of Participants With Vital Signs of Potential Clinical Concern in Part 1
Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.
Measured: Up to 29 days in Part 1
Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 1
Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 1 are presented.
Measured: Up to 29 days in Part 1
Number of Participants With Laboratory Values of Potential Clinical Concern in Part 1
Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct bilirubin, creatinine, sodium alanine, aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.
Measured: Up to 29 days in Part 1

Secondary outcomes (18)

Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC [0-24]) of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Time to Occurrence of Cmax (Tmax) of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Terminal Half-life (t1/2) of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of Danirixin for Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Maximum Observed Concentration (Cmax) of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Time to Maximum Observed Concentration (Tmax) of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Terminal Half-life (t1/2) of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Lag Time Before Observable Concentration (Tlag) of Danirixin for Part 2
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 2
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Measured: Up to 52 days in Part 2
Number of Participants With Vital Signs of Potential Clinical Concern in Part 2
Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.
Measured: Up to 52 days in Part 2
Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 2
Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 2 are presented.
Measured: Up to 52 days in Part 2
Number of Participants With Laboratory Values of Potential Clinical Concern in Part 2
Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate, Aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct, bilirubin, creatinine sodium alanine, Aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.
Measured: Up to 52 days in Part 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Mar 201825 Jul 2018

First posted7 Mar 2018
Study start7 Mar 2018
Primary completion25 Jul 2018
Study completion25 Jul 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Subjects will receive danirixin reference and test formulations in a cross-over manner.
Masking: None (open label)
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03457727
Sponsor's protocol ID: 207573
Status last verified: Apr 2021
First submitted: 1 Mar 2018
Last updated: 19 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study is available via the Clinical Study Data Request site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two Part, Randomized, Open-label, Cross Over Study in Healthy Elderly Participants to Evaluate the Relative Bioavailability of Hydrobromide Salt Tablet Formulations of Danirixin in the Fed and Fasted States, and to Evaluate the Effect of Food and Gastric Acid Secretion Suppression on Danirixin Pharmacokinetics Following Administration of Hydrobromide Salt Tablets
ClinicalTrials.gov ID: NCT03457727
Acronym / sponsor ID: 207573
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Danirixin, Healthy, Food effect, Relative Bioavailability, Hydrobromide Salt
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 7 Mar 2018 (actual)
Primary completion: 25 Jul 2018 (actual)
Study completion: 25 Jul 2018 (actual)
First posted: 7 Mar 2018 (actual)
Results: Posted 28 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3
Model description: Subjects will receive danirixin reference and test formulations in a cross-over manner.

Arm	Type	Receives
Subjects receiving danirixin: Part A	Experimental	Drug: DanirixinSubjects will receive a single oral dose of 50 mg danirixin reference and test formulations with food and 240 mL of water in a cross-over manner.
Subjects receiving danirixin without omeprazole: Part B	Experimental	Drug: DanirixinSubjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) in fasted or fed state in a cross-over manner.
Subjects receiving danirixin with omeprazole: Part B	Experimental	Drug: Danirixin, Drug: OmeprazoleSubjects will receive a single oral dose of 50 mg danirixin formulation (selected in Part A) along with once daily 40 mg OMP capsule in fasted or fed state in a cross-over manner.

Who may qualify

Ages: 65 to 80 years
Sex: All
Healthy volunteers: Accepted
Age groups: Older adult

Key inclusion criteria (8 listed)

Subjects must be 65 to 80 years of age inclusive, at the Screening Visit.
Subjects who are healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring or a subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives. Additionally, laboratory assessments that are specifically listed in the inclusion or exclusion criteria and are outside of the reference range can be repeated once during the screening period.
Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 34 kg per meter square (kg/m^2) (inclusive).
Male or female subjects will be included. A female subject 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.

Key exclusion criteria (25 listed)

Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test [TST; defined as a skin induration <5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history] or a positive (not indeterminate) QuantiFERON®-TB Gold test.
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
ALT >1.5x ULN

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DanirixinDanirixin is being developed as a potential anti-inflammatory agent for the treatment of chronic obstructive pulmonary disorder (COPD) and other inflammatory diseases and influenza. Danirixin reference (600 mg) or test formulation (475 or 600 mg or 600 mg with 5 percent HPMC) immediate release tablets will be administered by oral route in a cross-over manner.	Drug	Subjects receiving danirixin with omeprazole: Part B, Subjects receiving danirixin without omeprazole: Part B, Subjects receiving danirixin: Part A
OmeprazoleOmeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects.	Drug	Subjects receiving danirixin with omeprazole: Part B

Primary outcome

Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the pharmacokinetic (PK) profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Maximum Observed Concentration (Cmax) of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Blood samples were collected at the indicated time points after administration of study treatment to investigate the PK profile of Danirixin. PK parameters were calculated by standard non-compartmental analysis using WinNonlin based on actual sampling times.
Number of Participants With Any Adverse Event (AE) and Serious Adverse Events (SAEs) in Part 1
Time frame: Up to 29 days in Part 1
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Number of Participants With Vital Signs of Potential Clinical Concern in Part 1
Time frame: Up to 29 days in Part 1
Vital signs included systolic and diastolic blood pressure, temperature, respiratory rate and pulse rate were measured with participants in semi-supine position after 5 minutes rest.
Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 1
Time frame: Up to 29 days in Part 1
Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 1 are presented.
Number of Participants With Laboratory Values of Potential Clinical Concern in Part 1
Time frame: Up to 29 days in Part 1
Hematology parameters included platelet count, RBC Count, hemoglobin, hematocrit, MCV, MCH, %Reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils. Clinical chemistry parameters included potassium aspartate aminotransferase(AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT), total and direct bilirubin, creatinine, sodium alanine, aminotransferase, (ALT)/ Serum Glutamic-Pyruvic, Transaminase (SGPT), total protein, fasting glucose, calcium, alkaline phosphatase and albumin. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine.

18 secondary outcomes

Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC [0-24]) of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Time to Occurrence of Cmax (Tmax) of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Terminal Half-life (t1/2) of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of Danirixin for Part 1
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Maximum Observed Concentration (Cmax) of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Time to Maximum Observed Concentration (Tmax) of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Terminal Half-life (t1/2) of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Lag Time Before Observable Concentration (Tlag) of Danirixin for Part 2
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2
Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 2
Time frame: Up to 52 days in Part 2
Number of Participants With Vital Signs of Potential Clinical Concern in Part 2
Time frame: Up to 52 days in Part 2
Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 2
Time frame: Up to 52 days in Part 2
Number of Participants With Laboratory Values of Potential Clinical Concern in Part 2
Time frame: Up to 52 days in Part 2

Results and safety

Results posted to the registry on 28 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
DNX 50 mg 600RC/475DC/600DC/600DC-5% HPMC in Fed State	8	8
DNX 50mg 600RC/475DC/600DC/600DC-5% HPMC in Fasted State	8	8
DNX 50 mg 475 DC Under Fasted/Normal/Fat Meal/ Mono-fat Meal	0	0
DNX 50 mg 475 DC+OMP 40mg Under Fasted/Normal/Fat Meal State	0	0

Primary outcome: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1. Geometric mean (Geometric Coefficient of Variation). Unit: Hours*nanograms per milliliter

Measure	600RC High Fat n = 5	475DC High Fat n = 7	600DC High Fat n = 7	600DC 5%HPMC High Fat n = 6	600RC Fasted n = 6	475DC Fasted n = 7	600DC Fasted n = 8	600DC 5%HPMC Fasted n = 8
Value	6166.7 (19.20)	6052.9 (14.18)	5816.4 (22.99)	5996.1 (26.31)	11394.6 (30.07)	11285.7 (32.72)	10957.4 (31.55)	11230.8 (28.21)

Population analysed: PK Population includes all participants for whom a PK sample was obtained and analyzed. Only those participants with data available at specified time frame were analyzed.

Primary outcome: Maximum Observed Concentration (Cmax) of Danirixin for Part 1

Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1. Geometric mean (Geometric Coefficient of Variation). Unit: Nanograms/milliliter

Measure	600RC High Fat n = 8	475DC High Fat n = 8	600DC High Fat n = 8	600DC 5%HPMC High Fat n = 8	600RC Fasted n = 7	475DC Fasted n = 8	600DC Fasted n = 8	600DC 5%HPMC Fasted n = 8
Value	761.5 (27.22)	712.8 (20.53)	762.3 (37.23)	659.2 (47.40)	2708.2 (26.22)	2418.5 (27.78)	2607.1 (30.24)	2511.8 (24.19)

Population analysed: PK population. Only those participants with data available at specified time frame were analyzed

Primary outcome: Number of Participants With Any Adverse Event (AE) and Serious Adverse Events (SAEs) in Part 1

Time frame: Up to 29 days in Part 1. Count of participants. Unit: Participants

Measure	600RC High Fat n = 8	475DC High Fat n = 8	600DC High Fat n = 8	600DC 5%HPMC High Fat n = 8	600RC Fasted n = 8	475DC Fasted n = 8	600DC Fasted n = 8	600DC 5%HPMC Fasted n = 8
Any AE	1	0	0	0	2	1	1	1
Any SAE	0	0	0	0	0	0	0	0

Population analysed: Modified Intent-to-treat (mITT) Population includes all randomized participants

Primary outcome: Number of Participants With Vital Signs of Potential Clinical Concern in Part 1

Time frame: Up to 29 days in Part 1. Count of participants. Unit: Participants

Measure	600RC High Fat n = 8	475DC High Fat n = 8	600DC High Fat n = 8	600DC 5%HPMC High Fat n = 8	600RC Fasted n = 8	475DC Fasted n = 8	600DC Fasted n = 8	600DC 5%HPMC Fasted n = 8
Value	2	2	2	2	0	0	0	0

Population analysed: mITT Population

18 secondary outcomes are reported in the full results.

Adverse events

Time frame: On-Treatment serious adverse events (SAEs) and non-serious AEs (nSAEs) were collected from start of study treatment until 81 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
600RC High Fat	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
475DC High Fat	0 of 8 (0%)	0 of 8 (0%)	0 of 8
600DC High Fat	0 of 8 (0%)	0 of 8 (0%)	0 of 8
600DC 5%HPMC High Fat	0 of 8 (0%)	0 of 8 (0%)	0 of 8
600RC Fasted	0 of 8 (0%)	2 of 8 (25%)	0 of 8
475DC Fasted	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
600DC Fasted	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
600DC 5%HPMC Fasted	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
475DC-Fasted	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
475DC-Normal Meal	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
475DC-High Fat	0 of 12 (0%)	1 of 12 (8.3%)	0 of 12
475DC-MONO High Fat	0 of 12 (0%)	0 of 12 (0%)	0 of 12
475DC-Fasted OMP	0 of 11 (0%)	0 of 11 (0%)	0 of 11
475DC-Normal Meal OMP	0 of 11 (0%)	0 of 11 (0%)	0 of 11
475DC-High Fat OMP	0 of 12 (0%)	3 of 12 (25%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Danirixin and Omeprazole in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1 (time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03457727.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2021.