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NCT00464568

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

Completed Phase 2 Results posted Last updated 20 August 2018
What this trial tests

Phase 2 trial testing GSK256066 in Rhinitis, Allergic, Seasonal in 32 participants. Completed in 16 May 2007.

Timeline
28 March 2007
Primary endpoint
16 May 2007
16 May 2007

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Primary purposetreatment
Enrollment32
Start date28 March 2007
Primary completion16 May 2007
Estimated completion16 May 2007
Sites1 location across Germany

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 50, any sex, with Rhinitis, Allergic, Seasonal. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Messenger Ribonucleic Acid (mRNA) Concentrations as a Measure of Gene Expression Primary · Day 1

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

CREM
GroupValue95% CI
Placebo2625.5± 0.03
GSK256066 1 mcg2987.2± 0.03
GSK256066 10 mcg3134.2± 0.03
GSK256066 50 mcg3162.0± 0.03
GSK256066 200 mcg3727.0± 0.03
DUSP1
GroupValue95% CI
Placebo8771.4± 0.04
GSK256066 1 mcg12718.0± 0.04
GSK256066 10 mcg13569.4± 0.04
GSK256066 50 mcg15221.2± 0.04
GSK256066 200 mcg15310.1± 0.04
FOSL2
GroupValue95% CI
Placebo10550.0± 0.03
GSK256066 1 mcg15672.4± 0.03
GSK256066 10 mcg16039.4± 0.03
GSK256066 50 mcg17776.4± 0.03
GSK256066 200 mcg16374.4± 0.03
IRS2
GroupValue95% CI
Placebo3260.5± 0.05
GSK256066 1 mcg5052.0± 0.05
GSK256066 10 mcg5059.6± 0.05
GSK256066 50 mcg5671.2± 0.05
GSK256066 200 mcg5083.8± 0.05
NR4A2
GroupValue95% CI
Placebo703.3± 0.07
GSK256066 1 mcg1081.0± 0.07
GSK256066 10 mcg1316.8± 0.07
GSK256066 50 mcg1522.5± 0.07
GSK256066 200 mcg1427.1± 0.07
PDE4A
GroupValue95% CI
Placebo43.4± 0.05
GSK256066 1 mcg44.5± 0.05
GSK256066 10 mcg51.3± 0.05
GSK256066 50 mcg51.7± 0.05
GSK256066 200 mcg59.8± 0.05
RGS1
GroupValue95% CI
Placebo509.5± 0.06
GSK256066 1 mcg542.2± 0.06
GSK256066 10 mcg617.6± 0.06
GSK256066 50 mcg698.4± 0.06
GSK256066 200 mcg697.3± 0.06
SNF1LK
GroupValue95% CI
Placebo2502.7± 0.05
GSK256066 1 mcg6810.4± 0.05
GSK256066 10 mcg7608.3± 0.05
GSK256066 50 mcg8205.7± 0.05
GSK256066 200 mcg8317.7± 0.05
Mean Forced Expiratory Volume in One Second (FEV1) Secondary · Up to 9 weeks

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.

GroupValue95% CI
Placebo4.073± 0.9045
GSK256066 1 mcg4.116± 0.8506
GSK256066 10 mcg4.018± 0.8564
GSK256066 50 mcg4.151± 0.8726
GSK256066 200 mcg4.096± 0.8909
Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Over Study Period Secondary · Up to 9 weeks

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.

DBP
GroupValue95% CI
Placebo70.8± 6.06
GSK256066 1 mcg69.4± 6.33
GSK256066 10 mcg69.2± 6.67
GSK256066 50 mcg70.6± 7.24
GSK256066 200 mcg68.9± 6.83
SBP
GroupValue95% CI
Placebo117.0± 10.76
GSK256066 1 mcg117.0± 10.34
GSK256066 10 mcg113.8± 9.51
GSK256066 50 mcg118.9± 10.91
GSK256066 200 mcg115.1± 9.97
Mean Heart Rate Over Study Period Secondary · Up to 9 weeks

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.

GroupValue95% CI
Placebo58.8± 9.47
GSK256066 1 mcg59.7± 9.10
GSK256066 10 mcg57.9± 9.16
GSK256066 50 mcg60.5± 12.34
GSK256066 200 mcg57.8± 10.84
Change From Baseline in Electrocardiogram (ECG) Values Secondary · Baseline (Day 1) to 9 weeks

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

PR Interval, 1 hour post-dose
GroupValue95% CI
Placebo-1.10± 6.650
GSK256066 1 mcg-0.87± 6.962
GSK256066 10 mcg-0.13± 9.157
GSK256066 50 mcg1.73± 8.132
GSK256066 200 mcg1.81± 8.553
PR Interval, 4 hour post-dose
GroupValue95% CI
Placebo-4.06± 7.857
GSK256066 1 mcg-5.87± 11.374
GSK256066 10 mcg-3.00± 7.379
GSK256066 50 mcg-2.40± 10.081
GSK256066 200 mcg-5.74± 9.560
QRS Duration, 1 hour post-dose
GroupValue95% CI
Placebo-0.77± 3.783
GSK256066 1 mcg-0.27± 2.449
GSK256066 10 mcg-0.50± 3.172
GSK256066 50 mcg-1.40± 2.931
GSK256066 200 mcg0.06± 4.049
QRS Duration, 4 hour post-dose
GroupValue95% CI
Placebo-0.97± 3.996
GSK256066 1 mcg-0.93± 3.005
GSK256066 10 mcg-1.06± 3.835
GSK256066 50 mcg-1.40± 2.931
GSK256066 200 mcg0.13± 4.440
QT Interval, 1 hour post-dose
GroupValue95% CI
Placebo3.55± 10.865
GSK256066 1 mcg11.67± 13.996
GSK256066 10 mcg6.38± 13.645
GSK256066 50 mcg8.93± 12.213
GSK256066 200 mcg4.77± 11.851
QT Interval, 4 hour post-dose
GroupValue95% CI
Placebo-17.29± 16.113
GSK256066 1 mcg-11.40± 16.079
GSK256066 10 mcg-13.88± 12.638
GSK256066 50 mcg-15.07± 21.151
GSK256066 200 mcg-16.52± 18.147
QTcB, 1 hour post-dose
GroupValue95% CI
Placebo0.58± 13.393
GSK256066 1 mcg1.67± 11.689
GSK256066 10 mcg-2.94± 9.277
GSK256066 50 mcg1.23± 14.555
GSK256066 200 mcg1.03± 14.061
QTcB, 4 hour post-dose
GroupValue95% CI
Placebo-2.32± 14.063
GSK256066 1 mcg0.30± 18.646
GSK256066 10 mcg-4.44± 13.361
GSK256066 50 mcg-1.27± 15.726
GSK256066 200 mcg-2.32± 12.621
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Secondary · Up to 9 weeks

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

AE
GroupValue95% CI
Placebo7
GSK256066 1 mcg6
GSK256066 10 mcg6
GSK256066 50 mcg8
GSK256066 200 mcg10
SAE
GroupValue95% CI
Placebo0
GSK256066 1 mcg0
GSK256066 10 mcg0
GSK256066 50 mcg0
GSK256066 200 mcg0
Number of Participants With Hematology Values of Potential Clinical Concern Secondary · Up to 9 weeks

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 o

GroupValue95% CI
Overall Study4
Number of Participants With Clinical Chemistry Values of Potential Clinical Concern Secondary · Up to 9 weeks

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).

GroupValue95% CI
Overall Study4
Area Under the Plasma Drug Concentration Versus Time Curve (AUC0-last) of GSK256066 Secondary · Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

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.

GroupValue95% CI
GSK256066 10 mcg7.7± 58
GSK256066 50 mcg14.7± 59
GSK256066 200 mcg41.9± 97
AUC (0-last) of Active Metabolite GSK614917 Secondary · Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

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.

GroupValue95% CI
GSK256066 200 mcg12.7± 63.0
Maximum Observed Plasma Drug Concentration (Cmax) of GSK256066 Secondary · Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

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.

GroupValue95% CI
GSK256066 1 mcg6.3± 198
GSK256066 10 mcg5.1± 110
GSK256066 50 mcg5.9± 70
GSK256066 200 mcg20.4± 121
Cmax of Active Metabolite GSK614917 Secondary · Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1

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.

GroupValue95% CI
GSK256066 10 mcg2.7± 47.6
GSK256066 50 mcg2.4± 20.1
GSK256066 200 mcg5.2± 62.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 9 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/31 (0%)
Deaths:
GSK256066 1 mcg
Serious: 0/30 (0%)
Deaths:
GSK256066 10 mcg
Serious: 0/32 (0%)
Deaths:
GSK256066 50 mcg
Serious: 0/30 (0%)
Deaths:
GSK256066 200 mcg
Serious: 0/31 (0%)
Deaths:
Other adverse events (23 terms — click to expand)

ReactionSystemPlaceboGSK256066 1 mcgGSK256066 10 mcgGSK256066 50 mcgGSK256066 200 mcg
HeadacheNervous system disorders
RhinitisInfections and infestations
NasopharyngitisInfections and infestations
EpistaxisRespiratory, thoracic and mediastinal disorders
Eye pruritusEye disorders
DysgeusiaNervous system disorders
SinusitisInfections and infestations
Throat irritationRespiratory, thoracic and mediastinal disorders
Nasal necrosisRespiratory, thoracic and mediastinal disorders
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders
Ocular hyperaemiaEye disorders
PhotophobiaEye disorders
DiarrhoeaGastrointestinal disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
GingivitisGastrointestinal disorders
FatigueGeneral disorders
AcneSkin and subcutaneous tissue disorders
Heat rashSkin and subcutaneous tissue disorders
Idioventricular rhythmCardiac disorders
Skin lacerationInjury, poisoning and procedural complications
ListlessPsychiatric disorders
Postmenopausal haemorrhageReproductive system and breast disorders

Data from ClinicalTrials.gov NCT00464568 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Advances in targeting cyclic nucleotide phosphodiesterases.
    Maurice DH, Ke H, Ahmad F, Wang Y, et al · · 2014 · cited 597× · PMID 24687066 · DOI 10.1038/nrd4228
  2. Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules.
    Bondarev AD, Attwood MM, Jonsson J, Chubarev VN, et al · · 2022 · cited 52× · PMID 36506513 · DOI 10.3389/fphar.2022.1057083

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