Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2017-001073-16 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
GSK2269557 is being developed as an anti-inflammatory and anti-infective agent for the treatment of inflammatory airways diseases. This is the first study using a new formulation of GSK2269557 in healthy subjects and will evaluate the safety, tolerability and PK of a single dose of GSK2269557. Data derived from this study will inform on the PK profile and systemic exposure expected during Phase 2b. Approximately twelve healthy subjects will be randomized to receive a single dose of GSK2269557 750 micrograms (µg) or a single dose of GSK2269557 500 µg via the ELLIPTA® dry powder inhaler (DPI) formulated in a blend containing 0.4 percent magnesium stearate (MgSt) in 1:1 ratio. This randomized, parallel group study will be carried out in 3 phases, including screening phase, treatment phase and follow-up phase. The total study duration for each subject will be up to 6 weeks. ELLIPTA is a registered trademark of GlaxoSmithKline group of companies.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2269557 500 µg receivers | Experimental | Randomized healthy subjects will receive single dose of GSK2269557 500 µg via inhalation route via the ELLIPTA DPI. |
|
| GSK2269557 750 µg receivers | Experimental | Randomized healthy subjects will receive single dose of GSK2269557 750 µg via inhalation route via the ELLIPTA DPI. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2269557 500 µg | Drug | GSK2269557 is a potent and highly selective inhaled Phosphoinositide 3 Kinase delta inhibitor. Single dose of GSK2269557 500 µg will be administered to randomized subjects via inhalation route using ELLIPTA DPI. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean GSK2269557 Plasma Concentration | Whole blood samples of approximately 2 milliliters were collected for measurement of plasma concentrations of GSK2269557 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population which comprised of all randomized participants in the Safety Population and for whom a PK sample was obtained and analyzed. | Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
| Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2269557 | Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles. | Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
| Maximum Observed Plasma Drug Concentration (Cmax) and Concentration at Trough (Ctrough) of GSK2269557 | Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. | Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
| Time to Maximum Observed Plasma Drug Concentration (Tmax) and Terminal Half-life (t1/2) | Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Vital Signs of Potential Clinical Importance | Vital signs included blood pressure (systolic and diastolic blood pressure) and heart rate measurements and were assessed with the participant in a semi-supine position after 5 minutes rest. The potential clinical concern range values for vital signs were: systolic blood pressure (lower <85 millimeters of mercury and higher >160 millimeters of mercury), diastolic blood pressure (lower <45 millimeters of mercury and higher >100 millimeters of mercury) and heart rate (lower <40 beats per minute and higher >110 beats per minute). Number of participants with vital signs of potential clinical importance are presented. Safety Population comprised of all randomized participants who received at least one dose of study treatment. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Cambridge | CB2 0GG | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31076203 | Background | Wilson R, Templeton A, Leemereise C, Eames R, Banham-Hall E, Hessel EM, Cahn A. Safety, Tolerability, and Pharmacokinetics of a New Formulation of Nemiralisib Administered via a Dry Powder Inhaler to Healthy Individuals. Clin Ther. 2019 Jun;41(6):1214-1220. doi: 10.1016/j.clinthera.2019.04.008. Epub 2019 May 7. |
Not provided
Not provided
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 19 participants were screened for this study, of which 7 participants were screen failures and 12 participants were randomized to treatment. The reasons for screen failure were: did not meet inclusion/exclusion criteria (6 participants) and withdrawal by participant (1 participant).
The study was conducted at a single center in the United Kingdom from 15-June-2017 to 24-July-2017.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | GSK2269557 500 mcg | Eligible participants received a single dose of GSK2269557 500 micrograms (mcg) via the ELLIPTA dry powder inhaler (DPI) on Day 1. |
| FG001 | GSK2269557 750 mcg | Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | GSK2269557 500 mcg | Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1. |
| BG001 | GSK2269557 750 mcg | Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean GSK2269557 Plasma Concentration | Whole blood samples of approximately 2 milliliters were collected for measurement of plasma concentrations of GSK2269557 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population which comprised of all randomized participants in the Safety Population and for whom a PK sample was obtained and analyzed. | PK Population. | Posted | Mean | Standard Deviation | Picograms per milliliter | Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
|
Up to 12 days post-dose
AE and SAE were collected for the Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | GSK2269557 500 mcg | Eligible participants received a single dose of GSK2269557 500 mcg via the ELLIPTA DPI on Day 1. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 4, 2017 | Apr 19, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 8, 2017 | Apr 19, 2018 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
Not provided
Not provided
| ID | Term |
|---|---|
| C000629641 | Nemiralisib |
Not provided
Not provided
Not provided
Healthy subjects will be randomized to receive GSK2269557 750 µg or GSK2269557 500 µg.
Not provided
Not provided
This is a double-blind study and subjects and investigator will be blinded.
| GSK2269557 750 µg | Drug | GSK2269557 is a potent and highly selective inhaled Phosphoinositide 3 Kinase delta inhibitor. Single dose of GSK2269557 750 µg will be administered to randomized subjects via inhalation route using ELLIPTA DPI. |
|
| Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
| Up to Day 2 |
| Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance | Twelve-lead ECG was obtained using an ECG machine which automatically measured PR, QRS, QT and corrected QT (QTc) intervals. ECG parameters and their potential clinical importance range values were: absolute QTc interval (lower >450 milliseconds [msec]), absolute PR interval (lower <110 msec and upper >220 msec), absolute QRS interval (lower <75 msec and upper >110 msec). Number of participants with electrocardiogram (ECG) values of potential clinical importance are presented. | Up to Day 2 |
| Change From Baseline in Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1) | The maximal amount of air forcefully exhaled in 1 second (FEV1) and forced vital capacity (FVC) was measured using a spirometer. Baseline was latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline values from post-dose visit values. Mean change from Baseline in FVC and FEV1 is presented. | Baseline and Day 1 |
| Number of Participants With Hematology Abnormalities of Potential Clinical Importance | Hematology parameters and their potential clinical concern values were: Hematocrit (high flag: >0.54 and change from Baseline: decrease of 0.075), hemoglobin (high flag: >180 grams per Liter and change from Baseline: decrease of 25 grams per Liter), lymphocytes (low flag: <0.8*10^9 cells per Liter), neutrophil count (low flag: <1.5*10^9 cells per Liter), platelet count (low flag: <100*10^9 cells per Liter and high flag: >550*10^9 cells per Liter) and white blood cell count (low flag: <3*10^9 cells per Liter and high flag: >20*10^9 cells per Liter). Number of participants with hematology abnormalities of potential clinical importance are presented. | Up to Day 2 |
| Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Clinical chemistry parameters and their potential clinical concern range values were: calcium (low flag <2 millimoles/Liter [mmol/L] and high flag >2.75 mmol/L), creatinine (high flag >44.2 micromoles/Liter increase in change from Baseline), glucose (fasting) (<3 mmol/L and >9 mmol/L), potassium (low flag <3 mmol/L and high flag >5.5 mmol/L above ULN), sodium (low flag <130 mmol/L and high flag >150 mmol/L). Number of participants with clinical chemistry abnormalities of potential clinical importance are presented. | Up to Day 2 |
| 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 the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. | Up to 12 days post-dose |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | GSK2269557 750 mcg | Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1. |
|
|
| Primary | Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2269557 | Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Mean | Standard Deviation | Hours*picograms per milliliter | Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
|
|
|
| Primary | Maximum Observed Plasma Drug Concentration (Cmax) and Concentration at Trough (Ctrough) of GSK2269557 | Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. | PK Population. | Posted | Mean | Standard Deviation | Picograms per milliliter | Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
|
|
|
| Primary | Time to Maximum Observed Plasma Drug Concentration (Tmax) and Terminal Half-life (t1/2) | Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles. | PK Population. | Posted | Median | Full Range | Hours | Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose |
|
|
|
| Secondary | Number of Participants With Vital Signs of Potential Clinical Importance | Vital signs included blood pressure (systolic and diastolic blood pressure) and heart rate measurements and were assessed with the participant in a semi-supine position after 5 minutes rest. The potential clinical concern range values for vital signs were: systolic blood pressure (lower <85 millimeters of mercury and higher >160 millimeters of mercury), diastolic blood pressure (lower <45 millimeters of mercury and higher >100 millimeters of mercury) and heart rate (lower <40 beats per minute and higher >110 beats per minute). Number of participants with vital signs of potential clinical importance are presented. Safety Population comprised of all randomized participants who received at least one dose of study treatment. | Safety Population | Posted | Number | Participants | Up to Day 2 |
|
|
|
| Secondary | Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance | Twelve-lead ECG was obtained using an ECG machine which automatically measured PR, QRS, QT and corrected QT (QTc) intervals. ECG parameters and their potential clinical importance range values were: absolute QTc interval (lower >450 milliseconds [msec]), absolute PR interval (lower <110 msec and upper >220 msec), absolute QRS interval (lower <75 msec and upper >110 msec). Number of participants with electrocardiogram (ECG) values of potential clinical importance are presented. | Safety Population. | Posted | Number | Participants | Up to Day 2 |
|
|
|
| Secondary | Change From Baseline in Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1) | The maximal amount of air forcefully exhaled in 1 second (FEV1) and forced vital capacity (FVC) was measured using a spirometer. Baseline was latest pre-dose assessment. Change from Baseline was calculated by subtracting Baseline values from post-dose visit values. Mean change from Baseline in FVC and FEV1 is presented. | Safety Population. | Posted | Mean | Standard Deviation | Liters (L) | Baseline and Day 1 |
|
|
|
| Secondary | Number of Participants With Hematology Abnormalities of Potential Clinical Importance | Hematology parameters and their potential clinical concern values were: Hematocrit (high flag: >0.54 and change from Baseline: decrease of 0.075), hemoglobin (high flag: >180 grams per Liter and change from Baseline: decrease of 25 grams per Liter), lymphocytes (low flag: <0.8*10^9 cells per Liter), neutrophil count (low flag: <1.5*10^9 cells per Liter), platelet count (low flag: <100*10^9 cells per Liter and high flag: >550*10^9 cells per Liter) and white blood cell count (low flag: <3*10^9 cells per Liter and high flag: >20*10^9 cells per Liter). Number of participants with hematology abnormalities of potential clinical importance are presented. | Safety Population. | Posted | Number | Participants | Up to Day 2 |
|
|
|
| Secondary | Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance | Clinical chemistry parameters and their potential clinical concern range values were: calcium (low flag <2 millimoles/Liter [mmol/L] and high flag >2.75 mmol/L), creatinine (high flag >44.2 micromoles/Liter increase in change from Baseline), glucose (fasting) (<3 mmol/L and >9 mmol/L), potassium (low flag <3 mmol/L and high flag >5.5 mmol/L above ULN), sodium (low flag <130 mmol/L and high flag >150 mmol/L). Number of participants with clinical chemistry abnormalities of potential clinical importance are presented. | Safety Population. | Posted | Number | Participants | Up to Day 2 |
|
|
|
| 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 the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. 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. | Safety Population. | Posted | Number | Participants | Up to 12 days post-dose |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 3 |
| 6 |
| EG001 | GSK2269557 750 mcg | Eligible participants received a single dose of GSK2269557 750 mcg via the ELLIPTA DPI on Day 1. | 0 | 6 | 0 | 6 | 3 | 6 |
| Catheter site inflammation | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012120 | Respiration Disorders |
| AUC (0 to 24), n=6,6 |
|
|
| AUC (0 to inf), n=4,5 |
|
|
| t1/2, n=4,5 |
|
|