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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-002347-16 | EudraCT Number |
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GSK2269557 is being developed as an anti-inflammatory agent for the treatment of chronic obstructive pulmonary disease (COPD) and other inflammatory lung diseases such as asthma. This study is designed to investigate the recovery, excretion, and pharmacokinetics (PK) of (14 Carbon [C])-GSK2269557 administered as a single intravenous (IV) dose (concomitant with an inhaled non-radiolabelled dose) and as a single oral dose in 6 healthy male subjects. Subjects will receive [14C] radiolabelled GSK2269557 administered as IV infusion, with a nonradiolabelled dose of GSK2269557 via dry powder inhaler (DPI) in treatment period 1 and a single dose of [14C]-GSK2269557, administered as an oral solution in treatment period 2. There will be a washout period of at least 14 days after inhaled and IV dosing before subjects takes part in treatment period 2. The IV microtracer dose of GSK2269557 will be administered concomitant to an inhaled non-radiolabelled dose to ensure that the pharmacokinetics represent a clinically relevant dose. The total study duration will be up to 11 weeks, including a screening visit, 2 treatment periods and a follow-up visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects receiving GSK2269557 in treatment period 1 | Experimental | Eligible subjects will receive IV infusion of [14C] radiolabelled GSK2269557 with a single dose of 10 micrograms (µg) administered as single microtracer, concomitantly with an inhaled nonradiolabelled 1000 µg dose of GSK2269557. There will be a washout of at least 14 days after inhaled and IV dosing before subjects receive treatment 2. |
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| Subjects receiving GSK2269557 in treatment period 2 | Experimental | Eligible subjects will receive [14C]-GSK2269557 with a single dose of 800 µg, administered as an oral solution. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [14C]-GSK2269557 IV infusion | Drug | The [14C]-GSK2269557 solution will be available in dosing strength of 10 µg, administered as single dose IV infusion over 15 minutes. It will be prepared by dissolving a hemisuccinate salt (GSK2269557T) in normal saline. |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Infinite Time (0 to Inf) and AUC From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic (PK) Population comprised of participants in the APE Population who received at least one dose of study treatment and for whom a PK sample was obtained and analyzed. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (0 to Inf) and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. NA indicates that data is not available as single participant was analyzed. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Maximum Observed Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Cmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. |
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Inclusion Criteria:
Exclusion Criteria:
This study will include 6 healthy male subjects.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | NW10 7EW | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31649125 | Background | Harrell AW, Wilson R, Man YL, Riddell K, Jarvis E, Young G, Chambers R, Crossman L, Georgiou A, Pereira A, Kenworthy D, Beaumont C, Marotti M, Wilkes D, Hessel EM, Fahy WA. An Innovative Approach to Characterize Clinical ADME and Pharmacokinetics of the Inhaled Drug Nemiralisib Using an Intravenous Microtracer Combined with an Inhaled Dose and an Oral Radiolabel Dose in Healthy Male Subjects. Drug Metab Dispos. 2019 Dec;47(12):1457-1468. doi: 10.1124/dmd.119.088344. Epub 2019 Oct 24. |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD is available via the Clinical Study Data Request site (click on the link provided below)
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.
A total of 7 participants were screened, of which 1 participant was a reserve participant and was not used. The remaining 6 participants were enrolled.
The study was conducted at a single center in the United Kingdom from 14-November-2017 to 22-December-2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | All Study Participants | Participants received intravenous (IV) infusion of [14C] radiolabeled GSK2269557 along with a single dose of 10 micrograms (µg) administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557 in Treatment Period 1. There was a washout of at least 14 days. Participants received [14C]-GSK2269557 with a single dose of 800 µg, administered as an oral solution in Treatment Period 2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (8 Days) |
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| Washout Period (14 Days) |
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| Treatment Period 2 (15 Days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants received intravenous (IV) infusion of [14C] radiolabeled GSK2269557 along with a single dose of 10 micrograms (µg) administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557 in Treatment Period 1. There was a washout of at least 14 days. Participants received [14C]-GSK2269557 with a single dose of 800 µg, administered as an oral solution in Treatment Period 2. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Safety Population comprised of all participants in the All Participants Enrolled (APE) Population (All participants for whom a record exists on the study database; included both screened and unscreened participants but signed the informed consent form) who received at least one dose of study treatment. |
| 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 Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Infinite Time (0 to Inf) and AUC From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. Pharmacokinetic (PK) Population comprised of participants in the APE Population who received at least one dose of study treatment and for whom a PK sample was obtained and analyzed. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*picogram Equivalent per millilitre | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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Serious and non serious adverse events were evaluated up to 11 weeks
Safety Population was analyzed to collect serious adverse events (SAE) and non-serious adverse events (nSAE).
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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 | Nemi IH + 14C-Nemi IV | Participants received IV infusion of [14C] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Malaise | 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 | Oct 30, 2017 | Aug 16, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 9, 2018 | Aug 16, 2018 | SAP_001.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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This will be a 2-period, single-sequence crossover study. Subjects will receive IV and inhaled doses of GSK2269557 in treatment period 1 and oral dose of GSK2269557 in treatment period 2.
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This will be an open-label study. Hence, masking will not be provided to the subjects.
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| GSK2269557 via DPI | Drug | GSK2269557 DPI will be available with dosing strength of 1000 µg, administered as oral inhalation intended to inhale twice. It will be prepared by blending GSK2269557 hemisuccinate salt (GSK2269557H) with lactose and magnesium stearate. |
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| [14C]-GSK2269557 oral solution | Drug | The [14C]-GSK2269557 solution will be available with dosing strength of 800 µg, administered as single dose orally. It will be prepared by dissolving [14C]-GSK2269557 hemisuccinate salt (GSK2269557T) in water. |
|
| Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Tmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. NA indicates that data is not available as single participant was analyzed. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Urine samples and fecal samples were collected to measure total radiolabeled drug-related material excreted in urine and feces respectively. | Up to 168 hours |
| Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Urine samples and fecal samples were collected to measure total radiolabeled drug-related material excreted in urine and feces respectively. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Up to 336 hours |
| Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Cmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Tmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. Only those participants available at the indicated time points were analyzed represented by n=X in the category titles. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| t1/2 of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Clearance of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Inhaled Absolute Bioavailability (F) for Treatment Period 1 | Absolute bioavailability (F) was estimated for the inhaled doses for each participant and is reported. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
| Oral Absolute Bioavailability (F) for Treatment Period 2 | Absolute bioavailability (F) was estimated for the oral doses for each participant and is reported. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product (MP), whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. 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 or all events of possible drug induced liver injury with hyperbilirubinemia. | Up to 11 weeks |
| Number of Participants With Hematology Parameters of Potential Clinical Concern | Hematology parameters included basophils, eosinophils, erythrocytes, monocytes, hematocrit, hemoglobin, lymphocytes, neutrophil count, platelet count and white blood cells. Number of participants with hematology parameters of potential clinical concern are presented. | Up to 11 weeks |
| Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern | Clinical chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, chloride, cholesterol, gamma glutamyl transferase, globulin, protein, triglycerides, urate, albumin, calcium, creatinine, glucose, phosphorous, potassium, urea and sodium. Number of participants with clinical chemistry parameters of potential clinical concern are presented. | Up to 11 weeks |
| Number of Participants With Clinically Significant Urinalysis Findings | Urine samples were collected to detect the presence of bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Urinalysis also included measurement of specific gravity and pH. Number of participants with clinically significant urinalysis findings are presented. | Up to 168 hours |
| Number of Participants With Electrocardiogram Findings of Clinical Significance | Twelve-lead electrocardiogram was measured in a supine or semi-supine position after 5 minutes rest. Number of participants with electrocardiogram findings of clinical significance are presented. | Up to 11 weeks |
| Number of Participants With Vital Signs of Potential Clinical Concern | Vital signs were measured in a supine or semi-supine position after 5 minutes rest and included temperature, systolic and diastolic blood pressure and pulse and respiratory rate. Number of participants with vital signs of potential clinical concern are reported. | Up to 11 weeks |
| Mean |
| Standard Deviation |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Count of participants |
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Participants received IV infusion of [14C] radiolabeled GSK2269557 as a single dose of 10 µg administered as single microtracer, concomitantly with an inhaled non-radiolabeled 1000 µg dose of GSK2269557. |
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| Primary | AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (0 to Inf) and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (0 to t) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. NA indicates that data is not available as single participant was analyzed. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*picogram Equivalent per millilitre | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Primary | Maximum Observed Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram Equivalent per milliliter | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Primary | Cmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram Equivalent per milliliter | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Primary | Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Primary | Tmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Primary | Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. | PK Population. Only those participants available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Primary | Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. NA indicates that data is not available as single participant was analyzed. | PK Population. Only those participants available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Primary | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Urine samples and fecal samples were collected to measure total radiolabeled drug-related material excreted in urine and feces respectively. | PK Population. | Posted | Mean | Standard Deviation | Percentage of dose excreted | Up to 168 hours |
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| Primary | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Urine samples and fecal samples were collected to measure total radiolabeled drug-related material excreted in urine and feces respectively. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Mean | Standard Deviation | Percentage of dose excreted | Up to 336 hours |
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| Secondary | AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*picogram per milliliter | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Secondary | AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*picogram per milliliter | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Secondary | Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliter | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Secondary | Cmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picograms per milliliter | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Secondary | Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Secondary | Tmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Secondary | t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS, whereas GSK2269557 describes the parent GSK2269557 concentration derived via LC/MS. Only those participants available at the indicated time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Secondary | t1/2 of [14C]-GSK2269557 in Plasma for Treatment Period 2 | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | PK Population. Only those participants available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Secondary | Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | PK Population. Only those participants available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Secondary | Clearance of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | Blood samples were collected at indicated time points for pharmacokinetic analysis. For measured concentrations of GSK2269557 in blood plasma, the nomenclature [14C]-GSK2269557 describes the parent GSK2269557 concentration derived via analysis by LC+AMS. | PK Population. Only those participants available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Secondary | Inhaled Absolute Bioavailability (F) for Treatment Period 1 | Absolute bioavailability (F) was estimated for the inhaled doses for each participant and is reported. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Fraction of drug | Pre-dose and at 0 hour (post inhalation and pre-IV infusion), at the end of infusion and at 0.33, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96 and 168 hours after the start of infusion |
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| Secondary | Oral Absolute Bioavailability (F) for Treatment Period 2 | Absolute bioavailability (F) was estimated for the oral doses for each participant and is reported. Only those participants available at the specified time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Fraction of drug | Pre-dose and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96 and 168 h post-dose |
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| Secondary | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product (MP), whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. 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 or all events of possible drug induced liver injury with hyperbilirubinemia. | Safety Population. | Posted | Count of Participants | Participants | Up to 11 weeks |
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| Secondary | Number of Participants With Hematology Parameters of Potential Clinical Concern | Hematology parameters included basophils, eosinophils, erythrocytes, monocytes, hematocrit, hemoglobin, lymphocytes, neutrophil count, platelet count and white blood cells. Number of participants with hematology parameters of potential clinical concern are presented. | Safety Population. | Posted | Count of Participants | Participants | Up to 11 weeks |
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| Secondary | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern | Clinical chemistry parameters included alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, chloride, cholesterol, gamma glutamyl transferase, globulin, protein, triglycerides, urate, albumin, calcium, creatinine, glucose, phosphorous, potassium, urea and sodium. Number of participants with clinical chemistry parameters of potential clinical concern are presented. | Safety Population. | Posted | Count of Participants | Participants | Up to 11 weeks |
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| Secondary | Number of Participants With Clinically Significant Urinalysis Findings | Urine samples were collected to detect the presence of bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Urinalysis also included measurement of specific gravity and pH. Number of participants with clinically significant urinalysis findings are presented. | Safety Population. | Posted | Count of Participants | Participants | Up to 168 hours |
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| Secondary | Number of Participants With Electrocardiogram Findings of Clinical Significance | Twelve-lead electrocardiogram was measured in a supine or semi-supine position after 5 minutes rest. Number of participants with electrocardiogram findings of clinical significance are presented. | Safety Population. | Posted | Count of Participants | Participants | Up to 11 weeks |
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| Secondary | Number of Participants With Vital Signs of Potential Clinical Concern | Vital signs were measured in a supine or semi-supine position after 5 minutes rest and included temperature, systolic and diastolic blood pressure and pulse and respiratory rate. Number of participants with vital signs of potential clinical concern are reported. | Safety Population | Posted | Count of Participants | Participants | Up to 11 weeks |
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| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | 14C-Nemi Oral | Participants received solution of [14C] radiolabelled GSK2269557 as a single dose of 800 µg orally | 0 | 6 | 0 | 6 | 1 | 6 |
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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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 |
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| Title | Measurements |
|---|---|
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| Fe Feces, 72 to 96 hour |
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| Fe Feces, 96 to 120 hour |
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| Fe Feces, 120 to 144 hour |
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| Fe Feces, 144 to 168 hour |
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| Fe Urine, 0 to 6 hour |
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| Fe Urine, 6 to 24 hour |
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| Fe Urine, 24 to 48 hour |
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| Fe Urine, 48 to 72 hour |
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| Fe Urine, 72 to 96 hour |
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| Fe Urine, 96 to 120 hour |
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| Fe Urine, 120 to 144 hour |
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| Fe Urine, 144 to 168 hour |
|
| Fe Total (Urine+Feces), 0 to 24 hour |
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| Fe Total (Urine+Feces), 24 to 48 hour |
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| Fe Total (Urine+Feces), 48 to 72 hour |
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| Fe Total (Urine+Feces), 72 to 96 hour |
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| Fe Total (Urine+Feces), 96 to 120 hour |
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| Fe Total (Urine+Feces), 120 to 144 hour |
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| Fe Total (Urine+Feces), 144 to 168 hour |
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| Fe Feces, 48 to 72 hour; n=6 |
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| Fe Feces, 72 to 96 hour; n=6 |
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| Fe Feces, 96 to 120 hour; n=6 |
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| Fe Feces, 120 to 144 hour; n=6 |
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| Fe Feces, 144 to 168 hour; n=6 |
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| Fe Feces, 168 to 192 hour; n=6 |
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| Fe Feces, 192 to 216 hour; n=6 |
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| Fe Feces, 216 to 240 hour; n=6 |
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| Fe Feces, 240 to 264 hour; n=6 |
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| Fe Feces, 264 to 288 hour; n=5 |
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| Fe Feces, 288 to 312 hour; n=3 |
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| Fe Feces, 312 to 336 hour; n=3 |
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| Fe Urine, 0 to 6 hour; n=6 |
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| Fe Urine, 6 to 24 hour; n=6 |
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| Fe Urine, 24 to 48 hour; n=6 |
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| Fe Urine, 48 to 72 hour; n=6 |
|
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| Fe Urine, 72 to 96 hour; n=6 |
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| Fe Urine, 96 to 120 hour; n=6 |
|
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| Fe Urine, 120 to 144 hour; n=6 |
|
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| Fe Urine, 144 to 168 hour; n=6 |
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| Fe Urine, 168 to 192 hour; n=6 |
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| Fe Urine, 192 to 216 hour; n=6 |
|
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| Fe Urine, 216 to 240 hour; n=6 |
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| Fe Urine, 240 to 264 hour; n=6 |
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| Fe Urine, 264 to 288 hour; n=5 |
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| Fe Urine, 288 to 312 hour; n=3 |
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| Fe Urine, 312 to 336 hour; n=3 |
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| Fe Total (Urine+Feces), 0 to 24 hour; n=6 |
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| Fe Total (Urine+Feces), 24 to 48 hour; n=6 |
|
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| Fe Total (Urine+Feces), 48 to 72 hour; n=6 |
|
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| Fe Total (Urine+Feces), 72 to 96 hour; n=6 |
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| Fe Total (Urine+Feces), 96 to 120 hour; n=6 |
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| Fe Total (Urine+Feces), 120 to 144 hour; n=6 |
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| Fe Total (Urine+Feces), 144 to 168 hour; n=6 |
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| Fe Total (Urine+Feces), 168 to 192 hour; n=6 |
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| Fe Total (Urine+Feces), 192 to 216 hour; n=6 |
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| Fe Total (Urine+Feces), 216 to 240 hour; n=6 |
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| Fe Total (Urine+Feces), 240 to 264 hour; n=6 |
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| Fe Total (Urine+Feces), 264 to 288 hour; n=5 |
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| Fe Total (Urine+Feces), 288 to 312 hour; n=3 |
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| Fe Total (Urine+Feces), 312 to 336 hour; n=3 |
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| [14C]-GSK2269557: AUC (0 to inf), n=4 |
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| [14C]-GSK2269557: AUC (0 to t), n=6 |
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