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This current study is planned as a dedicated pharmacodynamic (effect of drug on the body) study to investigate the dose response in rhinitic subjects at doses where GSK256066 has been proven to work (200mcg) or expected to (50mcg) work. This study also aims to investigate the lower end of the predicted therapeutic range.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK256066 | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Messenger Ribonucleic Acid (mRNA) Concentrations as a Measure of Gene Expression | The effect of GSK256066 on ribonucleic acid (RNA) levels indicative of Phosphodiesterase-4 (PDE4) inhibition in nasal scrape samples and on protein biomarkers of PDE4 inhibition in lavage samples was evaluated. Nasal lavage and scrapes were taken 2 to 3 hour post morning dose; bilateral nasal lavage was conducted before the scrape. Nasal scrape samples were taken from alternate nostrils. The novel RNA markers presented are cAMP responsive element modulator (CREM), dual specificity phosphatase 1(DUSP1), fos-like antigen 2(FOSL2), insulin receptor substrate 2 (IRS2), nuclear receptor subfamily 4, group A, member 2 (NR4A2), Phosphodiesterase-4A (PDE4A), Regulator of G-protein signalling 1 (RGS1), Serine/threonine protein kinase SNF1 like kinase (SNF1LK). Nasal lavage cytospins were stained with a SNF1LK specific monoclonal antibody by indirect immunofluorescence. Adjusted Geometric Mean and Standard error logs are presented. | Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Forced Expiratory Volume in One Second (FEV1) | The FEV1 is the volume of air forcefully exhaled in 1 second. The highest FEV1 value amongst the three recorded FEV1 readings was used for all FEV1 calculations. FEV1 was recorded pre-dose and at follow-up. | Up to 9 weeks |
| Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Over Study Period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Berlin | 14050 | Germany |
Participants who were positive for grass pollen on radioallergosorbent and skin prick testing were enrolled. Participants underwent Screening 7 to 28 days prior to study start.
A total of 32 healthy adult females and males aged 18 to 50 years and having a positive history of seasonal allergic rhinitis (SAR) were enrolled. The study was conducted at a single center in Germany from 28-March-2007 to 16-May-2007.
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| ID | Title | Description |
|---|---|---|
| FG000 | Overall Study | Eligible participants received unit dose of nasal GSK256066 1 microgram (mcg) or 10 mcg or 50 mcg or 200 mcg or matching Placebo in any one of the five treatment periods in a randomized manner. Two treatment periods were separated by a 3 day washout period. Participants attended the unit on the morning of dosing and stayed until all study procedures were completed (approximately 4 hours) and were followed-up for maximum of 14 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | Eligible participants received unit dose of nasal GSK256066 1 mcg or 10 mcg or 50 mcg or 200 mcg or matching Placebo in any one of the five treatment periods in a randomized manner. Two treatment periods were separated by a 3 day washout period. Participants attended the unit on the morning of dosing and stayed until all study procedures were completed (approximately 4 hours) and were followed-up for maximum of 14 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Messenger Ribonucleic Acid (mRNA) Concentrations as a Measure of Gene Expression | The effect of GSK256066 on ribonucleic acid (RNA) levels indicative of Phosphodiesterase-4 (PDE4) inhibition in nasal scrape samples and on protein biomarkers of PDE4 inhibition in lavage samples was evaluated. Nasal lavage and scrapes were taken 2 to 3 hour post morning dose; bilateral nasal lavage was conducted before the scrape. Nasal scrape samples were taken from alternate nostrils. The novel RNA markers presented are cAMP responsive element modulator (CREM), dual specificity phosphatase 1(DUSP1), fos-like antigen 2(FOSL2), insulin receptor substrate 2 (IRS2), nuclear receptor subfamily 4, group A, member 2 (NR4A2), Phosphodiesterase-4A (PDE4A), Regulator of G-protein signalling 1 (RGS1), Serine/threonine protein kinase SNF1 like kinase (SNF1LK). Nasal lavage cytospins were stained with a SNF1LK specific monoclonal antibody by indirect immunofluorescence. Adjusted Geometric Mean and Standard error logs are presented. | All Subjects population comprised of all participants randomized to treatment who received at least one dose of study treatment (including placebo). | Posted | Geometric Mean | Standard Error | COPIES/50 nanogram (NG) | Day 1 |
Up to 9 weeks
On-treatment Serious adverse events (SAE) and non-serious adverse events (nSAE) are reported for the All Subjects population which comprised of all participants randomized to treatment who received at least one dose of study treatment (including placebo).
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 | Placebo | Participants received a single dose of aqueous nasal spray of GSK256066 matching placebo via intranasal route, 1 puff per nostril. The total duration of the study per participant was approximately 8 to 9 weeks (up to 4 weeks Screening and 3 weeks dosing (including washout) plus a Follow-up visit at least 7 days (and no more than 14 days) after the last treatment. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
Not provided
| ID | Term |
|---|---|
| D006255 | Rhinitis, Allergic, Seasonal |
| ID | Term |
|---|---|
| D065631 | Rhinitis, Allergic |
| D012220 | Rhinitis |
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C549469 | 6-((3-((dimethylamino)carbonyl)phenyl)sulfonyl)-8-methyl-4-((3-methyloxyphenyl)amino)-3-quinolinecarboxamide |
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Vital signs included SBP and DBP. SBP and DBP were measured pre-dose. The measurements were taken at 5 minutes interval during each treatment period. Vital signs measurements were made with the participant in a supine position having rested in this position for at least 5 minutes before the first reading at each time point. Measurements that deviated substantially from previous readings were repeated immediately. |
| Up to 9 weeks |
| Mean Heart Rate Over Study Period | Vital signs included heart rate. Heart rate was measured pre-dose. The measurements were taken at 5 minutes interval during each treatment period. Vital signs measurements were made with the participant in a supine position having rested in this position for at least 5 minutes before the first reading at each time point. Measurements that deviated substantially from previous readings were repeated immediately. | Up to 9 weeks |
| Change From Baseline in Electrocardiogram (ECG) Values | Electrocardiogram variables evaluated included PR interval, QRS duration, QT interval, QT corrected by Bazett's formula (QTcB), QT corrected by Fridericia's formula (QTcF) and RR interval. ECG was performed pre-dose, one hour and four hour post-dose. The ECG measurements were made with the participant in a supine position having rested in this position for at least 10 minutes before each time-point. Baseline was defined as the pre-dose measurement on Day 1. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values | Baseline (Day 1) to 9 weeks |
| 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 9 weeks |
| Number of Participants With Hematology Values of Potential Clinical Concern | Blood samples for hematology were taken before dosing. Whole blood samples were collected and processed according to the local procedures at site. The samples were transferred to the local laboratory for analysis. The participants with hematology of potential clinical concern are reported. The potential clinical concern ranges (low and high) were given as: for white blood cell count (clinical concern range: 3 to 20 giga cells/liter), neutrophils (normal range: 2.1 to 10.0 giga cells/liter), hemoglobin (clinical concern upper value: >180 grams/liter). Only those parameters for which at least one value of potential clinical concern was reported are summarized. | Up to 9 weeks |
| Number of Participants With Clinical Chemistry Values of Potential Clinical Concern | Blood samples for clinical chemistry were taken before dosing. Whole blood samples were collected and processed according to the local procedures at site. The samples were transferred to the local laboratory for analysis. The participants with clinical chemistry values of potential clinical concern are reported. The potential clinical concern ranges (low and high) were given as: for total bilirubin levels (clinical concern upper value: >31 micromole/liter) and inorganic phosphorus level (normal range: 0.7-1.5 millimole/liter). | Up to 9 weeks |
| Area Under the Plasma Drug Concentration Versus Time Curve (AUC0-last) of GSK256066 | The pharmacokinetics (PK) of GSK256066 were assessed in plasma by determining AUC(0-last). All participants who received at least one dose of the active investigational product provided at least one sample for plasma PK analysis. Blood samples for PK were collected pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose and analyzed for GSK256066. AUC (0-last) was not calculable for any participant at 1 mcg GSK256066 dose. | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
| AUC (0-last) of Active Metabolite GSK614917 | The PK of GSK256066 were assessed in plasma by determining AUC(0-last). All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. AUC (0-last) was not calculable in any participant at the 1, 10 or 50 mcg GSK256066 dose. | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
| Maximum Observed Plasma Drug Concentration (Cmax) of GSK256066 | The PK of GSK256066 were assessed in plasma by determining Cmax. All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. Blood samples for PK were collected pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose and analyzed for GSK256066. | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
| Cmax of Active Metabolite GSK614917 | The PK of GSK614917 were assessed in plasma by determining AUC(0-last). All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. C max was not calculable for any participant at the 1 mcg GSK256066 dose. | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
| Time to Maximum Observed Plasma Drug Concentration (Tmax) and Time to Last Observed Plasma Drug Concentration (Tlast) of GSK256066 | The PK of GSK256066 were assessed in plasma by determining Tmax and Tlast. All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. Blood samples for PK were collected pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose and analyzed for GSK256066. | Pre -dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
| Tmax and Tlast of Active Metabolite GSK614917 | The PK of GSK614917 were assessed in plasma by determining Tmax and Tlast. All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. Tmax and Tlast could not be determined for any participant at the 1 mcg GSK256066 dose. | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
| Nasal Lavage Concentrations of GSK256066 | Nasal lavage samples were taken 2 -3 hour post morning dose and analyzed for GSK256066. Quantifiable levels of GSK256066 were observed in nasal lavage samples obtained 2-3 hours post-dose. | Day 1 |
| Mean Levels of Total Vasodilator Stimulated Phosphoprotein (VASP) Protein, Phosphorylated(Phospho)157 VASP (pVASP) and phospho239 VASP in Lavage Cells | Nasal lavage were taken 2 to 3 hour post morning dose; bilateral nasal lavage was conducted before the scrape. Nasal lavage samples were analyzed to explore the effects of GSK256066 on novel protein biomarkers including pVASP. Markers indicative of PDE4 inhibition such as VASP protein levels and phospho157 VASP were also measured in this study, in lavage cells, following positive data in an enabling study which showed increases in such protein levels in participants with allergic rhinitis following a single intranasal dose of salbutamol. Nasal lavage data from earlier studies showed that pVASP157 is the best marker and not pVASP239. pVASP239 was therefore not collected or analyzed as planned. | Day 1 |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo | Eligible participants received a single dose of aqueous nasal spray of GSK256066 matching placebo via intranasal route, 1 puff per nostril and were followed-up up to maximum 14 days. |
| OG001 | GSK256066 1 mcg | Eligible participants received a single dose of GSK256066 1 mcg aqueous nasal spray via intranasal route, 1 puff of 0.5 mcg per nostril and were followed-up up to maximum 14 days. |
| OG002 | GSK256066 10 mcg | Eligible participants received a single dose of GSK256066 10 mcg aqueous nasal spray via intranasal route, 1 puff of 5 mcg per nostril and were followed-up up to maximum 14 days. |
| OG003 | GSK256066 50 mcg | Eligible participants received a single dose of GSK256066 50 mcg aqueous nasal spray via intranasal route, 1 puff of 25 mcg per nostril and were followed-up up to maximum 14 days. |
| OG004 | GSK256066 200 mcg | Eligible participants received a single dose of GSK256066 200 mcg aqueous nasal spray via intranasal route, 1 puff of 100 mcg per nostril and were followed-up up to maximum 14 days. |
|
|
|
| Secondary | Mean Forced Expiratory Volume in One Second (FEV1) | The FEV1 is the volume of air forcefully exhaled in 1 second. The highest FEV1 value amongst the three recorded FEV1 readings was used for all FEV1 calculations. FEV1 was recorded pre-dose and at follow-up. | All subjects population. | Posted | Mean | Standard Deviation | Liters (L) | Up to 9 weeks |
|
|
|
| Secondary | Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Over Study Period | Vital signs included SBP and DBP. SBP and DBP were measured pre-dose. The measurements were taken at 5 minutes interval during each treatment period. Vital signs measurements were made with the participant in a supine position having rested in this position for at least 5 minutes before the first reading at each time point. Measurements that deviated substantially from previous readings were repeated immediately. | All subjects population. | Posted | Mean | Standard Deviation | Millimetres of mercury (mmHg) | Up to 9 weeks |
|
|
|
| Secondary | Mean Heart Rate Over Study Period | Vital signs included heart rate. Heart rate was measured pre-dose. The measurements were taken at 5 minutes interval during each treatment period. Vital signs measurements were made with the participant in a supine position having rested in this position for at least 5 minutes before the first reading at each time point. Measurements that deviated substantially from previous readings were repeated immediately. | All subjects population. | Posted | Mean | Standard Deviation | Beats/minute | Up to 9 weeks |
|
|
|
| Secondary | Change From Baseline in Electrocardiogram (ECG) Values | Electrocardiogram variables evaluated included PR interval, QRS duration, QT interval, QT corrected by Bazett's formula (QTcB), QT corrected by Fridericia's formula (QTcF) and RR interval. ECG was performed pre-dose, one hour and four hour post-dose. The ECG measurements were made with the participant in a supine position having rested in this position for at least 10 minutes before each time-point. Baseline was defined as the pre-dose measurement on Day 1. Change from Baseline was calculated by subtracting Baseline values from post-Baseline values | All subjects population. | Posted | Mean | Standard Deviation | Millisecond (msec) | Baseline (Day 1) to 9 weeks |
|
|
|
| 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. | All subjects population. | Posted | Number | Participants | Up to 9 weeks |
|
|
|
| Secondary | Number of Participants With Hematology Values of Potential Clinical Concern | Blood samples for hematology were taken before dosing. Whole blood samples were collected and processed according to the local procedures at site. The samples were transferred to the local laboratory for analysis. The participants with hematology of potential clinical concern are reported. The potential clinical concern ranges (low and high) were given as: for white blood cell count (clinical concern range: 3 to 20 giga cells/liter), neutrophils (normal range: 2.1 to 10.0 giga cells/liter), hemoglobin (clinical concern upper value: >180 grams/liter). Only those parameters for which at least one value of potential clinical concern was reported are summarized. | All subjects population. | Posted | Number | Participants | Up to 9 weeks |
|
|
|
| Secondary | Number of Participants With Clinical Chemistry Values of Potential Clinical Concern | Blood samples for clinical chemistry were taken before dosing. Whole blood samples were collected and processed according to the local procedures at site. The samples were transferred to the local laboratory for analysis. The participants with clinical chemistry values of potential clinical concern are reported. The potential clinical concern ranges (low and high) were given as: for total bilirubin levels (clinical concern upper value: >31 micromole/liter) and inorganic phosphorus level (normal range: 0.7-1.5 millimole/liter). | All subjects population. | Posted | Number | Participants | Up to 9 weeks |
|
|
|
| Secondary | Area Under the Plasma Drug Concentration Versus Time Curve (AUC0-last) of GSK256066 | The pharmacokinetics (PK) of GSK256066 were assessed in plasma by determining AUC(0-last). All participants who received at least one dose of the active investigational product provided at least one sample for plasma PK analysis. Blood samples for PK were collected pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose and analyzed for GSK256066. AUC (0-last) was not calculable for any participant at 1 mcg GSK256066 dose. | PK parameter population comprised of all participants from the PK Concentration population (comprised of all participants from the All Subjects population for whom blood or nasal samples were taken for assaying study drug) for whom PK parameters were available. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram*hour per milliliter (pg*hr/mL) | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
|
|
|
| Secondary | AUC (0-last) of Active Metabolite GSK614917 | The PK of GSK256066 were assessed in plasma by determining AUC(0-last). All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. AUC (0-last) was not calculable in any participant at the 1, 10 or 50 mcg GSK256066 dose. | PK parameter population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg * hr/mL | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
|
|
|
| Secondary | Maximum Observed Plasma Drug Concentration (Cmax) of GSK256066 | The PK of GSK256066 were assessed in plasma by determining Cmax. All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. Blood samples for PK were collected pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose and analyzed for GSK256066. | PK Parameter population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram per mililiter (pg/mL) | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
|
|
|
| Secondary | Cmax of Active Metabolite GSK614917 | The PK of GSK614917 were assessed in plasma by determining AUC(0-last). All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. C max was not calculable for any participant at the 1 mcg GSK256066 dose. | PK parameter population. Only those participants with data available at the indicated time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | pg/mL | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
|
|
|
| Secondary | Time to Maximum Observed Plasma Drug Concentration (Tmax) and Time to Last Observed Plasma Drug Concentration (Tlast) of GSK256066 | The PK of GSK256066 were assessed in plasma by determining Tmax and Tlast. All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. Blood samples for PK were collected pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose and analyzed for GSK256066. | PK Parameter population. Only those participants with data available at the indicated time points were analyzed. | Posted | Median | Full Range | Hour | Pre -dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
|
|
|
| Secondary | Tmax and Tlast of Active Metabolite GSK614917 | The PK of GSK614917 were assessed in plasma by determining Tmax and Tlast. All participants who received at least one dose of the study drug provided at least one sample for plasma PK analysis. Tmax and Tlast could not be determined for any participant at the 1 mcg GSK256066 dose. | PK parameter population. | Posted | Median | Full Range | Hour | Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1 |
|
|
|
| Secondary | Nasal Lavage Concentrations of GSK256066 | Nasal lavage samples were taken 2 -3 hour post morning dose and analyzed for GSK256066. Quantifiable levels of GSK256066 were observed in nasal lavage samples obtained 2-3 hours post-dose. | PK concentration population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Picogram/milliliter (pg/mL) | Day 1 |
|
|
|
| Secondary | Mean Levels of Total Vasodilator Stimulated Phosphoprotein (VASP) Protein, Phosphorylated(Phospho)157 VASP (pVASP) and phospho239 VASP in Lavage Cells | Nasal lavage were taken 2 to 3 hour post morning dose; bilateral nasal lavage was conducted before the scrape. Nasal lavage samples were analyzed to explore the effects of GSK256066 on novel protein biomarkers including pVASP. Markers indicative of PDE4 inhibition such as VASP protein levels and phospho157 VASP were also measured in this study, in lavage cells, following positive data in an enabling study which showed increases in such protein levels in participants with allergic rhinitis following a single intranasal dose of salbutamol. Nasal lavage data from earlier studies showed that pVASP157 is the best marker and not pVASP239. pVASP239 was therefore not collected or analyzed as planned. | All subjects population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Percentage | Day 1 |
|
|
|
|
| 0 |
| 31 |
| 7 |
| 31 |
| EG001 | GSK256066 1 mcg | Participants received a single dose of GSK256066 1 mcg aqueous nasal spray via intranasal route, 1 puff of 0.5 mcg per nostril. The total duration of the study per participant was approximately 8 to 9 weeks (up to 4 weeks Screening and 3 weeks dosing (including washout) plus a Follow-up visit at least 7 days (and no more than 14 days) after the last treatment. | 0 | 30 | 6 | 30 |
| EG002 | GSK256066 10 mcg | Participants received a single dose of GSK256066 10 mcg aqueous nasal spray via intranasal route, 1 puff of 5 mcg per nostril. The total duration of the study per participant was approximately 8 to 9 weeks (up to 4 weeks Screening and 3 weeks dosing (including washout) plus a Follow-up visit at least 7 days (and no more than 14 days) after the last treatment. | 0 | 32 | 6 | 32 |
| EG003 | GSK256066 50 mcg | Participants received a single dose of GSK256066 50 mcg aqueous nasal spray via intranasal route, 1 puff of 25 mcg per nostril. The total duration of the study per participant was approximately 8 to 9 weeks (up to 4 weeks Screening and 3 weeks dosing (including washout) plus a Follow-up visit at least 7 days (and no more than 14 days) after the last treatment. | 0 | 30 | 8 | 30 |
| EG004 | GSK256066 200 mcg | Participants received a single dose of GSK256066 200 mcg aqueous nasal spray via intranasal route, 1 puff of 100 mcg per nostril. The total duration of the study per participant was approximately 8 to 9 weeks (up to 4 weeks Screening and 3 weeks dosing (including washout) plus a Follow-up visit at least 7 days (and no more than 14 days) after the last treatment. | 0 | 31 | 10 | 31 |
| Dysgeusia | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Nasal necrosis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA 10.0 | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA 10.0 | Systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA 10.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Gingivitis | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Heat rash | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Idioventricular rhythm | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Listless | Psychiatric disorders | MedDRA 10.0 | Systematic Assessment |
|
| Postmenopausal haemorrhage | Reproductive system and breast disorders | MedDRA 10.0 | 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.
| D012130 |
| Respiratory Hypersensitivity |
| D010038 | Otorhinolaryngologic Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| SBP |
|
| PR Interval, 4 hour post-dose |
|
| QRS Duration, 1 hour post-dose |
|
| QRS Duration, 4 hour post-dose |
|
| QT Interval, 1 hour post-dose |
|
| QT Interval, 4 hour post-dose |
|
| QTcB, 1 hour post-dose |
|
| QTcB, 4 hour post-dose |
|
| QTcF, 1 hour post-dose |
|
| QTcF, 4 hour post-dose |
|
| RR Interval, 1 hour post-dose |
|
| RR Interval, 4 hour post-dose |
|
| SAE |
|
| Tmax |
|
|
|
| pVASP |
|
|
| Mixed effects analysis of variance model |
| 0.95084 |
| Mean treatment difference |
| -0.3816 |
| Standard Deviation |
| 9.00754 |
The mean treatment difference was calculated as treatment minus placebo |
| Superiority or Other |
| Placebo Vs GSK256066 50 mcg: VASP | Mixed effects analysis of variance model | 0.53499 | Mean treatment difference | 0.0256 | Standard Deviation | 9.24118 | The mean treatment difference was calculated as treatment minus placebo | Superiority or Other |
| Placebo vs GSK256066 200 mcg: VASP | Mixed effects analysis of variance model | 0.81527 | Mean treatment difference | -1.3371 | Standard Deviation | 7.54590 | The mean treatment difference was calculated as treatment minus placebo | Superiority or Other |
| Placebo Vs GSK256066 1 mcg: pVASP | Mixed effects analysis of variance model | 0.32998 | Mean treatment difference | -2.8053 | Standard Deviation | 10.88217 | The mean treatment difference was calculated as treatment minus placebo | Superiority or Other |
| Placebo vs GSK256066 10 mcg: pVASP | Mixed effects analysis of variance model | 0.65729 | Mean treatment difference | -1.6602 | Standard Deviation | 12.30724 | The mean treatment difference was calculated as treatment minus placebo | Superiority or Other |
| Placebo vs GSK256066 50 mcg: pVASP | Mixed effects analysis of variance model | 0.89831 | Mean treatment difference | 0.1560 | Standard Deviation | 4.73976 | The mean treatment difference was calculated as treatment minus placebo | Superiority or Other |
| Placebo vs GSK256066 200 mcg: pVASP | Mixed effects analysis of variance model | 0.84479 | Mean treatment difference | -1.5165 | Standard Deviation | 12.70748 | The mean treatment difference was calculated as treatment minus placebo | Superiority or Other |