A 5-way Treatment Period Trial of Single Doses of Intranasal GSK256066 in Patients With Rhinitis

Browse trials for

• Rhinitis 1,105
• Rhinitis, Allergic, Seasonal 392
• Rhinitis, Allergic 1,030

Keywords

• Seasonal allergic rhinitis,
• hayfever

Rhinitis

1,105 studies on the registry are indexed under Rhinitis; 65 are open to participants now.

This study's enrollment of 32 is below the median of 89 across 906 interventional studies indexed under Rhinitis.

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Interventions

• DrugGSK256066

Primary outcomes

1. 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.

   Time frame: Day 1

Secondary outcomes

1. 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.

   Time frame: Up to 9 weeks

2. 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.

   Time frame: Up to 9 weeks

3. 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.

   Time frame: Up to 9 weeks

4. 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

   Time frame: Baseline (Day 1) to 9 weeks

5. 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.

   Time frame: Up to 9 weeks

6. 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.

   Time frame: Up to 9 weeks

7. 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).

   Time frame: Up to 9 weeks

8. 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.

   Time frame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

9. 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.

   Time frame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

10. 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.

    Time frame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

11. 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.

    Time frame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

12. 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.

    Time frame: Pre -dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

13. 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.

    Time frame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

14. 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.

    Time frame: Day 1

15. 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.

    Time frame: Day 1

Baseline characteristics