Clinical trial NCT00464568: A 5-way Treatment Period Trial of Single Doses of Intranasal GSK256066 in Patients With Rhinitis
Official title: A Randomised, Open, Placebo-controlled 5-way Crossover Trial of Single Doses of Intranasal GSK256066 in Subjects With Seasonal Allergic Rhinitis (SAR).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rhinitis, Allergic, Seasonal
Keywords: Seasonal allergic rhinitis,
hayfever
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-04-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* The subject is healthy.
* Body mass index less than 29.0 kg/m² , weight range of 55.0kg (females 50kg) to 95.0kg inclusive.
* They have a history of hayfever (repeated yearly episodes).
* They have a positive skin prick test for grass pollen at or within the 12 months preceding the screening visit.
* They have a positive radioallergosorbent test for grass pollen at or within the 12 months preceding the screening visit.
* non-smokers.
* They must have a baseline FEV1\>80% predicted and a baseline FEV1(maximum recorded value)/ forced vital capacity (FVC) (maximum recorded value)\>70%
* They are capable of giving informed consent
* They are available to complete all study measurements.

Exclusion Criteria:

* Pregnant or nursing females.
* Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception.
* The subject has structural nasal abnormalities or nasal polyposis.
* Any respiratory disease other than mild stable asthma that is controlled with occasional use of as-needed short-acting beta-agonists and associated with normal lung function.
* The subject has a history of drug or other allergy that may contraindicate participation.
* The subject has participated in a study with a new molecular entity during the previous 4 months or in any clinical study in the previous 3 months
* The subject is concurrently participating in another clinical study and is exposed to an investigational or a non-investigational drug or device.
* The subject has a screening QTc value \>450msec, PR interval outside the range 120 to 240msec or an ECG that is not suitable for QT measurements.In addition subjects will be excluded if they have a history of atrial and ventricular arrhythmia.
* The subject has a supine blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg) at screening.
* The subject has donated a unit of blood (450mL) within the previous 3 months or intends to donate within 3 months of completing the study.
* The subject is currently taking regular (or a course of) medication whether prescribed or not, including steroids, vitamins, and herbal remedies (e.g. St. John's Wort). Paracetamol (\<2g/day) and occasional as needed use of short-acting beta agonists is permitted.
* Past or present disease which may affect study. outcome
* The subject regularly, or on average, drinks more than 4 units of alcohol per day - where 1 unit = ½ pint of beer (284mL), or 1 glass of wine (125mL), or 1 measure of spirit (25mL).
* The subject is at risk of non-compliance with the study procedures/restrictions.
* The subject has Hepatitis B, Hepatitis C, or HIV virus.

Primary outcomes:
measure: Mean Messenger Ribonucleic Acid (mRNA) Concentrations as a Measure of Gene Expression
timeFrame: Day 1
Secondary outcomes:
measure: Mean Forced Expiratory Volume in One Second (FEV1)
timeFrame: Up to 9 weeks
measure: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Over Study Period
timeFrame: Up to 9 weeks
measure: Mean Heart Rate Over Study Period
timeFrame: Up to 9 weeks
measure: Change From Baseline in Electrocardiogram (ECG) Values
timeFrame: Baseline (Day 1) to 9 weeks
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to 9 weeks
measure: Number of Participants With Hematology Values of Potential Clinical Concern
timeFrame: Up to 9 weeks
measure: Number of Participants With Clinical Chemistry Values of Potential Clinical Concern
timeFrame: Up to 9 weeks
measure: Area Under the Plasma Drug Concentration Versus Time Curve (AUC0-last) of GSK256066
timeFrame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1
measure: AUC (0-last) of Active Metabolite GSK614917
timeFrame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1
measure: Maximum Observed Plasma Drug Concentration (Cmax) of GSK256066
timeFrame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1
measure: Cmax of Active Metabolite GSK614917
timeFrame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1
measure: Time to Maximum Observed Plasma Drug Concentration (Tmax) and Time to Last Observed Plasma Drug Concentration (Tlast) of GSK256066
timeFrame: Pre -dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1
measure: Tmax and Tlast of Active Metabolite GSK614917
timeFrame: Pre-dose, 15 minutes, 30 minutes, 1, 2, 3 and 4 hours post-dose on Day 1
measure: Nasal Lavage Concentrations of GSK256066
timeFrame: Day 1
measure: Mean Levels of Total Vasodilator Stimulated Phosphoprotein (VASP) Protein, Phosphorylated(Phospho)157 VASP (pVASP) and phospho239 VASP in Lavage Cells
timeFrame: Day 1
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: