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

NCT00464568 | Completed Phase 2 Results

• 1 other identifier: IPR109764
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Rhinitis, Allergic, Seasonal

Keywords

Seasonal allergic rhinitis,; hayfever

Outcome Measures

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.

  Day 1

Secondary Outcomes (15)

• Mean Forced Expiratory Volume in One Second (FEV1)

  Up to 9 weeks

• Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Over Study Period

  Up to 9 weeks

• Mean Heart Rate Over Study Period

  Up to 9 weeks

• Change From Baseline in Electrocardiogram (ECG) Values

  Baseline (Day 1) to 9 weeks

• Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  Up to 9 weeks

Interventions

GSK256066 DRUG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Rhinitis, Allergic, Seasonal

Interventions

6-((3-((dimethylamino)carbonyl)phenyl)sulfonyl)-8-methyl-4-((3-methyloxyphenyl)amino)-3-quinolinecarboxamide

Condition Hierarchy (Ancestors)

Rhinitis, Allergic; Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2007
• First Posted: April 23, 2007
• Study Start: March 28, 2007
• Primary Completion: May 16, 2007
• Study Completion: May 16, 2007
• Last Updated: August 20, 2018
• Results First Posted: August 21, 2017

Record last verified: 2018-07

Locations

DE (1)