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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Danirixin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | 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. | Up to 29 days in Part 1 |
| Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 1 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
IPD for this study is available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
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.
Danirixin hemihydrate salt tablet formulation manufactured using roller compaction (RC) was compared to test formulations manufactured by direct compression (DC) with an excipient hydroxypropyl methylcellulose (HPMC) to evaluate the most appropriate formulation/dosing regimen. A total of 40 participants were enrolled in the study.
This two-part study assessed the relative bioavailability of Danirixin (DNX) tablet formulations along with effect of food and gastric acid secretion suppression on DNX pharmacokinetics. This study was conducted at a single center in the United States from 07-Mar-2018 to 25-Jul-2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | DNX 50 mg 600RC/475DC/600DC/600DC-5% HPMC in Fed State | Participants received a sequence of the following: single oral dose of 50 milligrams (mg) DNX hydrobromide (HBr) hemihydrate tablet formulation (600 mg tablet manufactured by RC [600 RC]) on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (475 mg tablet manufactured by DC [475 DC]) on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (600 DC) on Day 1 of treatment period 3 and 50 mg DNX HBr hemihydrate 600 DC tablet formulation with containing 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fed state (with a high fat meal). The treatment periods were separated by a washout period of 5 days. |
| FG001 | DNX 50mg 600RC/475DC/600DC/600DC-5% HPMC in Fasted State | Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 600 RC on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC on Day 1 of treatment period 2, a single oral dose 50 mg DNX HBr hemihydrate 600 DC on Day 1 of treatment period 3 and a single oral dose of 50 mg DNX HBr hemihydrate 600 DC with 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fasted state. The treatment periods were separated by a washout period of 5 days. |
| FG002 | DNX 50 mg 475 DC Under Fasted/Normal/Fat Meal/ Mono-fat Meal | Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC tablet formulation in fasted state on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with normal meal on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with high fat meal in treatment period 3, followed by a single oral dose of 50 mg DNX HBr monohydrate 475 DC with high fat meal in treatment period 4. The treatment periods were separated by a washout period of 5 days. |
| FG003 | DNX 50 mg 475 DC+OMP 40mg Under Fasted/Normal/Fat Meal State | Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC in fasted state along with 40 mg omeprazole (OMP) during treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with normal meal in treatment period 2 and a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with high fat meal in treatment period 3. The treatment periods were separated by a washout period of 5 days. OMP was administered from Day -4 of each treatment period through washout periods. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1, Period 1 (1 Day) |
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| Part 1, Washout Period 1 (5 Days) |
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| Part 1, Period 2 (1 Day) |
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| Part 1, Washout Period 2 (5 Days) |
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| Part 1, Period 3 (1 Day) |
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| Part 1, Washout Period 3 (5 Days) |
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| Part 1, Period 4 (1 Day) |
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| Part 2, Period 1 (1 Day) |
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| Part 2, Washout Period 1 (5 Days) |
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| Part 2, Period 2 (1 Day) |
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| Part 2, Washout Period 2 (5 Days) |
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| Part 2, Period 3 (1 Day) |
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| Part 2, Washout Period 3 (5 Days) |
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| Part 2, Period 4 (1 Day) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | DNX 50 mg 600RC/475DC/600DC/600DC-5% HPMC in Fed State | Participants received a sequence of the following: single oral dose of 50 milligrams (mg) DNX hydrobromide (HBr) hemihydrate tablet formulation (600 mg tablet manufactured by RC [600 RC]) on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (475 mg tablet manufactured by DC [475 DC]) on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate tablet formulation (600 DC) on Day 1 of treatment period 3 and 50 mg DNX HBr hemihydrate 600 DC tablet formulation with containing 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fed state (with a high fat meal). The treatment periods were separated by a washout period of 5 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanograms per milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
|
On-Treatment serious adverse events (SAEs) and non-serious AEs (nSAEs) were collected from start of study treatment until 81 days
On-Treatment SAEs and nSAEs were reported for mITT Population.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 600RC High Fat | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation along with a high fat meal |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vessel puncture site haematoma | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 22, 2018 | Jul 16, 2019 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 6, 2018 | Jul 14, 2019 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C581951 | danirixin |
| D009853 | Omeprazole |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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Subjects will receive danirixin reference and test formulations in a cross-over manner.
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This will be an open-label study and blinding will not be performed.
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|
| Omeprazole | Drug | Omeprazole is used as an antacid. OMP 40 mg delayed-release capsule will be administered by oral route to randomized subjects. |
|
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. |
| 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. | Up to 29 days 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Up to 52 days in Part 2 |
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| BG001 | DNX 50mg 600RC/475DC/600DC/600DC-5% HPMC in Fasted State | Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 600 RC on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC on Day 1 of treatment period 2, a single oral dose 50 mg DNX HBr hemihydrate 600 DC on Day 1 of treatment period 3 and a single oral dose of 50 mg DNX HBr hemihydrate 600 DC with 5 percent HPMC on Day 1 of treatment period 4. All the formulations were administered in fasted state. The treatment periods were separated by a washout period of 5 days. |
| BG002 | DNX 50 mg 475 DC Under Fasted/Normal/Fat Meal/ Mono-fat Meal | Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC tablet formulation in fasted state on Day 1 of treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with normal meal on Day 1 of treatment period 2, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC along with high fat meal in treatment period 3, followed by a single oral dose of 50 mg DNX HBr monohydrate 475 DC with high fat meal in treatment period 4. The treatment periods were separated by a washout period of 5 days. |
| BG003 | DNX 50 mg 475 DC+OMP 40mg Under Fasted/Normal/Fat Meal State | Participants received a sequence of the following: single oral dose of 50 mg DNX HBr hemihydrate 475 DC in fasted state along with 40 mg omeprazole (OMP) during treatment period 1, a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with normal meal in treatment period 2 and a single oral dose of 50 mg DNX HBr hemihydrate 475 DC and 40 mg OMP along with high fat meal in treatment period 3. The treatment periods were separated by a washout period of 5 days. OMP was administered from Day -4 of each treatment period through washout periods. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Count of Participants |
|
| OG001 | 475DC High Fat | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal |
| OG002 | 600DC High Fat | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal |
| OG003 | 600DC 5%HPMC High Fat | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal |
| OG004 | 600RC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition |
| OG005 | 475DC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition |
| OG006 | 600DC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition |
| OG007 | 600DC 5%HPMC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition |
|
|
| Primary | 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. | PK population. Only those participants with data available at specified time frame were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms/milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
|
|
|
| Primary | 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. | Modified Intent-to-treat (mITT) Population includes all randomized participants | Posted | Count of Participants | Participants | Up to 29 days in Part 1 |
|
|
|
| Primary | 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. | mITT Population | Posted | Count of Participants | Participants | Up to 29 days in Part 1 |
|
|
|
| Primary | 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. | mITT Population | Posted | Count of Participants | Participants | Up to 29 days in Part 1 |
|
|
|
| Primary | 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. | mITT Population | Posted | Count of Participants | Participants | Up to 29 days in Part 1 |
|
|
|
| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanograms/milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
|
|
|
| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanograms/milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
|
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Mean | Standard Deviation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Mean | Standard Deviation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Mean | Standard Deviation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 1 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanograms/milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanograms/milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*nanograms/milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms/milliliter | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | PK population. Only those participants with data available at specified time points were analyzed | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours in Part 2 |
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| Secondary | 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. | mITT Population | Posted | Count of Participants | Participants | Up to 52 days in Part 2 |
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| Secondary | 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. | mITT Population | Posted | Count of Participants | Participants | Up to 52 days in Part 2 |
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| Secondary | 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. | mITT Population | Posted | Count of Participants | Participants | Up to 52 days in Part 2 |
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| Secondary | 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. | mITT Population | Posted | Count of Participants | Participants | Up to 52 days in Part 2 |
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|
| 0 |
| 8 |
| 0 |
| 8 |
| 1 |
| 8 |
| EG001 | 475DC High Fat | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation along with high fat meal | 0 | 8 | 0 | 8 | 0 | 8 |
| EG002 | 600DC High Fat | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation along with high fat meal | 0 | 8 | 0 | 8 | 0 | 8 |
| EG003 | 600DC 5%HPMC High Fat | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation along with high fat meal | 0 | 8 | 0 | 8 | 0 | 8 |
| EG004 | 600RC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 RC tablet formulation under fasted condition | 0 | 8 | 0 | 8 | 2 | 8 |
| EG005 | 475DC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation under fasted condition | 0 | 8 | 0 | 8 | 1 | 8 |
| EG006 | 600DC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet formulation under fasted condition | 0 | 8 | 0 | 8 | 1 | 8 |
| EG007 | 600DC 5%HPMC Fasted | Participants received a single oral dose of DNX 50 mg HBr hemihydrate 600 DC tablet with 5 percent HPMC formulation under fasted condition | 0 | 8 | 0 | 8 | 1 | 8 |
| EG008 | 475DC-Fasted | Participants received a single dose of DNX 50 mg HBr hemihydrate 475 DC tablet formulation in fasted state | 0 | 12 | 0 | 12 | 1 | 12 |
| EG009 | 475DC-Normal Meal | Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with normal meal | 0 | 12 | 0 | 12 | 1 | 12 |
| EG010 | 475DC-High Fat | Participants received DNX 50 mg HBr hemihydrate 475 DC formulation along with high fat meal | 0 | 12 | 0 | 12 | 1 | 12 |
| EG011 | 475DC-MONO High Fat | Participants received DNX 50 mg HBr monohydrate 475 DC with 5 percent HPMC formulation along with high fat meal | 0 | 12 | 0 | 12 | 0 | 12 |
| EG012 | 475DC-Fasted OMP | Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP under fasted condition | 0 | 11 | 0 | 11 | 0 | 11 |
| EG013 | 475DC-Normal Meal OMP | Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with normal meal | 0 | 11 | 0 | 11 | 0 | 11 |
| EG014 | 475DC-High Fat OMP | Participants received DNX 50 mg HBr hemihydrate 475 DC formulation and OMP along with high fat meal | 0 | 12 | 0 | 12 | 3 | 12 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Abnormal faeces | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Any SAE |
|
| Any SAE |
|