Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
GSK2269557, Pharmacokinetics, Radiolabel, Healthy, Excretion, Bioavailability
Brief summary
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.
Interventions
DRUG[14C]-GSK2269557 IV infusion
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.
DRUGGSK2269557 via DPI
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.
DRUG[14C]-GSK2269557 oral solution
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This will be an open-label study. Hence, masking will not be provided to the subjects.
Intervention model description
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.
Eligibility
Sex/Gender
MALE
Age
30 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be 30 to 55 years of age inclusive, at the time of signing the informed consent. * Subjects who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring; A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * A history of regular bowel movements (averaging one or more bowel movements per day). * Body weight \>= 50 kilograms (Kg) and body mass index (BMI) within the range 19.0-31.0 kg per meter square (kg/m\^2) (inclusive). * Male subjects will be included. * Subjects with female partners of childbearing potential must agree to use contraception during the treatment period, from the time of first dose of study medication until follow-up, and refrain from donating sperm during this period. * Capable of giving signed informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Up to 168 hours | Urine samples and fecal samples were collected to measure total radiolabeled drug-related material excreted in urine and feces respectively. |
| 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 | 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 | 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. |
| 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 | 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 | 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. |
| Maximum Observed Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis. |
| Cmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis. |
| Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis. |
| Tmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis. |
| Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis. |
| Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | 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 | Blood samples were collected at indicated time points for pharmacokinetic analysis. NA indicates that data is not available as single participant was analyzed. |
| Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Up to 336 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inhaled Absolute Bioavailability (F) for Treatment Period 1 | 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 | 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. |
| Oral Absolute Bioavailability (F) for Treatment Period 2 | 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 | 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. |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Up to 11 weeks | 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. |
| Number of Participants With Hematology Parameters of Potential Clinical Concern | Up to 11 weeks | 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. |
| AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | 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 | 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. |
| Number of Participants With Clinically Significant Urinalysis Findings | Up to 168 hours | 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. |
| Number of Participants With Electrocardiogram Findings of Clinical Significance | Up to 11 weeks | 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. |
| Number of Participants With Vital Signs of Potential Clinical Concern | Up to 11 weeks | 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. |
| Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern | Up to 11 weeks | 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. |
| AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2 | 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 | 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. |
| Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | 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 | 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. |
| Cmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | 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 | 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. |
| Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | 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 | 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. |
| Tmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | 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 | 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. |
| t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | 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 | 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. |
| t1/2 of [14C]-GSK2269557 in Plasma for Treatment Period 2 | 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 | 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. |
| Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | 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 | 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. |
| Clearance of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | 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 | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
The study was conducted at a single center in the United Kingdom from 14-November-2017 to 22-December-2017.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 43.3 Years STANDARD_DEVIATION 10.03 |
| Race/Ethnicity, Customized African American/African Heritage | 2 Count of participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 4 Count of participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | 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 | AUC (0 to inf), n=3 | 812.8550 Hour*picogram Equivalent per millilitre | Geometric Coefficient of Variation 8.17885 |
| Nemi IH + 14C-Nemi IV | 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 | AUC (0 to t), n=6 | 770.3316 Hour*picogram Equivalent per millilitre | Geometric Coefficient of Variation 17.70272 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | 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 | AUC (0 to inf), n=1 | 34749.40 Hour*picogram Equivalent per millilitre | — |
| Nemi IH + 14C-Nemi IV | 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 | AUC (0 to t), n=6 | 31730.13 Hour*picogram Equivalent per millilitre | Geometric Coefficient of Variation 35.715 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Cmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | 703.5192 Picogram Equivalent per milliliter | Geometric Coefficient of Variation 24.43331 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Maximum Observed Concentration (Cmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | 204.4057 Picogram Equivalent per milliliter | Geometric Coefficient of Variation 52.32698 |
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.
Time frame: 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
Population: PK Population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | 56.9152 Hours | Geometric Coefficient of Variation 7.69827 |
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.
Time frame: 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
Population: PK Population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Terminal Phase Half-life (t1/2) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | 39.6279 Hours |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Time of Occurrence of Cmax (Tmax) of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 1 | 0.2333 Hours |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Tmax of Total Drug-related Material (Radioactivity) in Plasma for Treatment Period 2 | 7.0000 Hours |
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.
Time frame: Up to 168 hours
Population: PK Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Feces, 48 to 72 hour | 18.1265 Percentage of dose excreted | Standard Deviation 12.9767 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Feces, 72 to 96 hour | 28.0481 Percentage of dose excreted | Standard Deviation 18.22334 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Feces, 144 to 168 hour | 51.6981 Percentage of dose excreted | Standard Deviation 15.4678 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 0 to 6 hour | 2.1567 Percentage of dose excreted | Standard Deviation 0.83754 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 6 to 24 hour | 5.1183 Percentage of dose excreted | Standard Deviation 1.53825 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 24 to 48 hour | 7.6850 Percentage of dose excreted | Standard Deviation 2.04159 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 120 to 144 hour | 12.3607 Percentage of dose excreted | Standard Deviation 2.56693 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Feces, 0 to 24 hour | 0.3961 Percentage of dose excreted | Standard Deviation 0.83271 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Feces, 24 to 48 hour | 2.1998 Percentage of dose excreted | Standard Deviation 3.77158 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Feces, 96 to 120 hour | 33.7465 Percentage of dose excreted | Standard Deviation 19.02044 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Feces, 120 to 144 hour | 45.2398 Percentage of dose excreted | Standard Deviation 14.63248 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 48 to 72 hour | 9.3483 Percentage of dose excreted | Standard Deviation 2.26387 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 72 to 96 hour | 10.7150 Percentage of dose excreted | Standard Deviation 2.4664 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 96 to 120 hour | 11.6400 Percentage of dose excreted | Standard Deviation 2.5279 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Urine, 144 to 168 hour | 12.9205 Percentage of dose excreted | Standard Deviation 2.57056 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Total (Urine+Feces), 0 to 24 hour | 5.5145 Percentage of dose excreted | Standard Deviation 1.30554 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Total (Urine+Feces), 24 to 48 hour | 9.8848 Percentage of dose excreted | Standard Deviation 3.03062 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Total (Urine+Feces), 48 to 72 hour | 27.4748 Percentage of dose excreted | Standard Deviation 13.02973 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Total (Urine+Feces), 72 to 96 hour | 38.7631 Percentage of dose excreted | Standard Deviation 18.40877 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Total (Urine+Feces), 96 to 120 hour | 45.3865 Percentage of dose excreted | Standard Deviation 19.01459 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Total (Urine+Feces), 120 to 144 hour | 57.6005 Percentage of dose excreted | Standard Deviation 14.46954 |
| Nemi IH + 14C-Nemi IV | Urinary and Faecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 1 | Fe Total (Urine+Feces), 144 to 168 hour | 64.6186 Percentage of dose excreted | Standard Deviation 15.25339 |
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.
Time frame: Up to 336 hours
Population: PK Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 48 to 72 hour; n=6 | 40.9583 Percentage of dose excreted | Standard Deviation 28.48392 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 312 to 336 hour; n=3 | 81.1500 Percentage of dose excreted | Standard Deviation 3.57979 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 24 to 48 hour; n=6 | 2.7183 Percentage of dose excreted | Standard Deviation 0.73249 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 168 to 192 hour; n=6 | 5.1383 Percentage of dose excreted | Standard Deviation 1.16426 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 192 to 216 hour; n=6 | 5.2950 Percentage of dose excreted | Standard Deviation 1.16156 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 216 to 240 hour; n=6 | 5.4700 Percentage of dose excreted | Standard Deviation 1.20854 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 240 to 264 hour; n=6 | 5.5617 Percentage of dose excreted | Standard Deviation 1.24856 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 264 to 288 hour; n=5 | 5.4760 Percentage of dose excreted | Standard Deviation 1.35858 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 288 to 312 hour; n=3 | 5.7800 Percentage of dose excreted | Standard Deviation 1.43293 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 24 to 48 hour; n=6 | 17.3550 Percentage of dose excreted | Standard Deviation 21.303 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 48 to 72 hour; n=6 | 44.3833 Percentage of dose excreted | Standard Deviation 28.28365 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 72 to 96 hour; n=6 | 52.7817 Percentage of dose excreted | Standard Deviation 29.36619 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 96 to 120 hour; n=6 | 65.1233 Percentage of dose excreted | Standard Deviation 17.8525 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 192 to 216 hour; n=6 | 82.3867 Percentage of dose excreted | Standard Deviation 3.98209 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 216 to 240 hour; n=6 | 83.0633 Percentage of dose excreted | Standard Deviation 3.3933 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 240 to 264 hour; n=6 | 84.3533 Percentage of dose excreted | Standard Deviation 3.17528 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 312 to 336 hour; n=3 | 86.9633 Percentage of dose excreted | Standard Deviation 2.16207 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 0 to 24 hour; n=6 | 3.81330 Percentage of dose excreted | Standard Deviation 7.16484 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 24 to 48 hour; n=6 | 14.6367 Percentage of dose excreted | Standard Deviation 21.64607 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 72 to 96 hour; n=6 | 48.8217 Percentage of dose excreted | Standard Deviation 29.60581 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 96 to 120 hour; n=6 | 60.7617 Percentage of dose excreted | Standard Deviation 18.24192 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 120 to 144 hour; n=6 | 64.1667 Percentage of dose excreted | Standard Deviation 19.65337 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 144 to 168 hour; n=6 | 72.4217 Percentage of dose excreted | Standard Deviation 6.66365 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 168 to 192 hour; n=6 | 75.1117 Percentage of dose excreted | Standard Deviation 5.29605 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 192 to 216 hour; n=6 | 77.0917 Percentage of dose excreted | Standard Deviation 4.5909 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 216 to 240 hour; n=6 | 77.5933 Percentage of dose excreted | Standard Deviation 4.12513 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 240 to 264 hour; n=6 | 78.7917 Percentage of dose excreted | Standard Deviation 3.82906 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 264 to 288 hour; n=5 | 78.6820 Percentage of dose excreted | Standard Deviation 4.07492 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Feces, 288 to 312 hour; n=3 | 80.9500 Percentage of dose excreted | Standard Deviation 3.78747 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 0 to 6 hour; n=6 | 0.3867 Percentage of dose excreted | Standard Deviation 0.09668 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 6 to 24 hour; n=6 | 1.7017 Percentage of dose excreted | Standard Deviation 0.42995 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 48 to 72 hour; n=6 | 3.4250 Percentage of dose excreted | Standard Deviation 0.89063 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 72 to 96 hour; n=6 | 3.9600 Percentage of dose excreted | Standard Deviation 0.9798 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 96 to 120 hour; n=6 | 4.3617 Percentage of dose excreted | Standard Deviation 1.02918 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 120 to 144 hour; n=6 | 4.6717 Percentage of dose excreted | Standard Deviation 1.09549 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 144 to 168 hour; n=6 | 4.9217 Percentage of dose excreted | Standard Deviation 1.12583 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Urine, 312 to 336 hour; n=3 | 5.8133 Percentage of dose excreted | Standard Deviation 1.4559 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 0 to 24 hour; n=6 | 5.5150 Percentage of dose excreted | Standard Deviation 7.01205 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 120 to 144 hour; n=6 | 68.8383 Percentage of dose excreted | Standard Deviation 19.24589 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 144 to 168 hour; n=6 | 77.3433 Percentage of dose excreted | Standard Deviation 6.27302 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 168 to 192 hour; n=6 | 80.2500 Percentage of dose excreted | Standard Deviation 4.74848 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 264 to 288 hour; n=5 | 84.158 Percentage of dose excreted | Standard Deviation 3.25412 |
| Nemi IH + 14C-Nemi IV | Urinary and Fecal Cumulative Excretion as a Percentage of the Total Radioactive Dose Administered Over Time for Treatment Period 2 | Fe Total (Urine+Feces), 288 to 312 hour; n=3 | 86.7300 Percentage of dose excreted | Standard Deviation 2.44851 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2 | AUC (0 to t), n=6 | 16913.06 Hour*picogram per milliliter | Geometric Coefficient of Variation 53.841 |
| Nemi IH + 14C-Nemi IV | AUC (0 to Inf) and AUC (0 to t) of [14C]-GSK2269557 in Plasma for Treatment Period 2 | AUC (0 to inf), n=4 | 25107.96 Hour*picogram per milliliter | Geometric Coefficient of Variation 46.31 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | GSK2269557: AUC (0 to inf), n=6 | 33374.56 Hour*picogram per milliliter | Geometric Coefficient of Variation 33.19 |
| Nemi IH + 14C-Nemi IV | AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | GSK2269557: AUC (0 to t), n=6 | 28425.82 Hour*picogram per milliliter | Geometric Coefficient of Variation 34.474 |
| Nemi IH + 14C-Nemi IV | AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | [14C]-GSK2269557: AUC (0 to inf), n=4 | 750.5798 Hour*picogram per milliliter | Geometric Coefficient of Variation 48.2776 |
| Nemi IH + 14C-Nemi IV | AUC (0 to Inf) and AUC (0 to t) of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | [14C]-GSK2269557: AUC (0 to t), n=6 | 546.4731 Hour*picogram per milliliter | Geometric Coefficient of Variation 45.31868 |
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.
Time frame: 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
Population: PK Population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Clearance of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | 10.7849 Liters per hour | Geometric Coefficient of Variation 46.70161 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Cmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | 398.8822 Picograms per milliliter | Geometric Coefficient of Variation 27.81929 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | GSK2269557 | 5258.98 Picograms per milliliter | Geometric Coefficient of Variation 62.819 |
| Nemi IH + 14C-Nemi IV | Cmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | [14C]-GSK2269557 | 205.6264 Picograms per milliliter | Geometric Coefficient of Variation 57.91419 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Inhaled Absolute Bioavailability (F) for Treatment Period 1 | Inhaled F (0 to inf); n=4 | 0.3807 Fraction of drug | Geometric Coefficient of Variation 19.65374 |
| Nemi IH + 14C-Nemi IV | Inhaled Absolute Bioavailability (F) for Treatment Period 1 | Inhaled F (0 to t); n=6 | 0.4213 Fraction of drug | Geometric Coefficient of Variation 21.8441 |
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.
Time frame: Up to 11 weeks
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 0 Participants |
| Nemi IH + 14C-Nemi IV | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 0 Participants |
| 14C-Nemi Oral | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | AE | 1 Participants |
| 14C-Nemi Oral | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | SAE | 0 Participants |
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.
Time frame: Up to 11 weeks
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern | 0 Participants |
| 14C-Nemi Oral | Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern | 0 Participants |
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.
Time frame: Up to 168 hours
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Number of Participants With Clinically Significant Urinalysis Findings | 0 Participants |
| 14C-Nemi Oral | Number of Participants With Clinically Significant Urinalysis Findings | 0 Participants |
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.
Time frame: Up to 11 weeks
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Number of Participants With Electrocardiogram Findings of Clinical Significance | 0 Participants |
| 14C-Nemi Oral | Number of Participants With Electrocardiogram Findings of Clinical Significance | 0 Participants |
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.
Time frame: Up to 11 weeks
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Number of Participants With Hematology Parameters of Potential Clinical Concern | 2 Participants |
| 14C-Nemi Oral | Number of Participants With Hematology Parameters of Potential Clinical Concern | 1 Participants |
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.
Time frame: Up to 11 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Number of Participants With Vital Signs of Potential Clinical Concern | Low temperature | 1 Participants |
| Nemi IH + 14C-Nemi IV | Number of Participants With Vital Signs of Potential Clinical Concern | High respiratory rate | 1 Participants |
| 14C-Nemi Oral | Number of Participants With Vital Signs of Potential Clinical Concern | High respiratory rate | 0 Participants |
| 14C-Nemi Oral | Number of Participants With Vital Signs of Potential Clinical Concern | Low temperature | 0 Participants |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Oral Absolute Bioavailability (F) for Treatment Period 2 | Oral F (0 to inf); n=4 | 0.3515 Fraction of drug | Geometric Coefficient of Variation 3.35095 |
| Nemi IH + 14C-Nemi IV | Oral Absolute Bioavailability (F) for Treatment Period 2 | Oral F (0 to t); n=6 | 0.3261 Fraction of drug | Geometric Coefficient of Variation 12.77892 |
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.
Time frame: 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
Population: PK Population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | t1/2 of [14C]-GSK2269557 in Plasma for Treatment Period 2 | 50.8028 Hours | Geometric Coefficient of Variation 40.16665 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | [14C]-GSK2269557 | 54.7223 Hours | Geometric Coefficient of Variation 35.9897 |
| Nemi IH + 14C-Nemi IV | t1/2 of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | GSK2269557 | 58.4408 Hours | Geometric Coefficient of Variation 16.8415 |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nemi IH + 14C-Nemi IV | Tmax of [14C]-GSK2269557 in Plasma for Treatment Period 2 | 6.0000 Hours |
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.
Time frame: 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
Population: PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | GSK2269557 | 0.0333 Hours |
| Nemi IH + 14C-Nemi IV | Tmax of Parent GSK2269557 and [14C]-GSK2269557 in Plasma for Treatment Period 1 | [14C]-GSK2269557 | 0.2333 Hours |
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.
Time frame: 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
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Nemi IH + 14C-Nemi IV | Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | Vss | 727.7102 Liters | Geometric Coefficient of Variation 11.24581 |
| Nemi IH + 14C-Nemi IV | Volume of Distribution of Parent [14C]-GSK2269557 After IV Dose Only in Plasma | Vz | 851.4423 Liters | Geometric Coefficient of Variation 13.9822 |