Clinical trial NCT00368576: A Study To Determine The Effect Of SB-480848 On Asthma
Official title: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Repeat Dose Study to Assess the Effect of SB-480848 on Overall Asthma Control in Adult Subjects With Persistent Asthma Controlled on Stable, Low-dose, Inhaled Corticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Atherosclerosis
Keywords: SB-480848
methacholine challenge
asthma
inhaled steroid
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-08-24
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to compare the effects of SB-480848 with placebo in subjects with asthma.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects who have documented persistent asthma for at least 3 months
* Subjects must have been on a stable, low-dose ICS for a minimum of 4 weeks prior to the screening visit.
* Aged 18-65 years, at screening
* FEV1 greater than or equal to 70% predicted (ECCS, 1993)
* Subjects must show an increase in FEV1 greater than or equal to 12% (and an absolute change \>200mL) within 30 minutes following inhalation of 4 puffs of albuterol/salbutamol or 1 nebulized treatment of 2.5mg or have historical, documented evidence of reversibility, within 12 months prior to screening
* Subjects must be willing to replace their inhaled, short-acting β2-agonist with study provided albuterol/salbutamol
* Patient must be capable of giving informed consent and comply with the study requirements and timetable.

Inclusion Criteria following run in period (Prior to randomisation) Subjects will be screened based on the inclusion and exclusion criteria noted above.

During the run-in period \[Day -14 to Day 1\], subjects will be asked to maintain a diary card and document the number of puffs of rescue inhaled, short-acting β2-agonists taken, asthma-related symptoms and night time awakenings as well as morning and evening PEF measurements.

On the morning of Day 0, subjects will be eligible for randomisation into the study if all of the following criteria are met:

* Subjects required, on average less than or 2 puffs per day of study provided albuterol/ salbutamol during the last 7-day period prior to Day 0 \[from Day -7 to Day 1\]
* Subjects had asthma symptoms on less than or 5 out of the last 7 consecutive days of the run-in period
* FEV1 greater than or equal to 70% predicted (ECCS, 1993).
* FEV1 must be within ± 15% of the FEV1 value at beginning of screening.
* Compliance with completion of the diary card.

Exclusion criteria:

* The patient has life threatening asthma. A research patient must not have been hospitalized two or more times in the last year prior to Day 0 due to asthma and must not have been hospitalized within 6 months prior to Day 0
* Subjects with daily asthma-related symptoms.
* Subjects taking any of the medications listed in the protocol for the listed interval prior to the screening visit or during the study:
* Subjects with historical or current evidence of any other disease.
* Subjects with clinically significant abnormal findings on physical exam or other screening procedures.
* Subjects who have received an investigational product within 30 days or 5 half-lives \[whichever is longer\] prior to the first dose of study medication
* Subjects who have tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV.
* Subjects with history of drug or alcohol abuse
* Positive drug (not related to known medications the subject is taking at time of screening), alcohol or cotinine/carbon monoxide (CO) test at screening or at Day 0
* Subjects with a history of regularly drinking more than 2 (females)/3 (males) units of alcohol a day.
* Pregnant or nursing female subjects.
* Female subjects of childbearing potential with an unwillingness to agree to one of the methods of contraception listed in the protocol.
* Subjects who suffer from any medical condition which in the opinion of the investigator would compromise patient safety or ability to comply with study procedures
* Subjects who are current smokers or have given up smoking within the previous six months or who have a smoking history \> 10 pack years.
* Subjects with history of an upper or lower respiratory tract infection or symptoms (including the common cold) within 2 weeks prior to first dose of study medication
* Subjects who have donated more than 500ml of blood within 56 days prior to the first dose of study medication
* Subjects who are currently receiving potent 3A4 inhibitors be excluded.
* Subjects on β-adrenergic receptor blockers within 3 months prior to screening visit
* Subjects previously hospitalized as a result of a methacholine challenge

Primary outcomes:
measure: FEV1
timeFrame: 6 hours post-dose, Days 7, 14 and 21
Secondary outcomes:
measure: Methacholine challenge Amounts of certain chemicals/proteins in blood Amount of drug in the blood
timeFrame: before dosing and after 21 days of dosing
measure: Measurements of FEV1 following single doses of SB-480848 and placebo.
measure: Measurements of PC20 on Day 21 +24hrs after dosing with SB-480848 and placebo.
timeFrame: Day 21 +24hrs after dosing
measure: Blood drug levels of SB-553253 [metabolite of SB-480848] may be assessed, as appropriate.
measure: Urinary leukotriene concentrations after 21 days of dosing with SB-480848 and Placebo.
timeFrame: after 21 days
measure: Blood levels of LpPLA2 and CD62 concentrations over 21-day dosing period with SB-480848 and placebo
timeFrame: over 21-day dosing period
measure: Measurements of FEF25-75 and peak expiratory flow following single and repeat oral doses of SB-480848.
measure: Assessment of vitals, ECGs, safety labs and number of puffs of rescue inhaled, short-acting β2-agonists taken, asthma-related symptoms and night time awakenings, number of subjects withdrawn due to worsening of asthma on SB- 480848 and placebo.
Other outcomes:
Locations:
city: Cypress
country: United States
facility: GSK Investigational Site
state: California
city: Normal
country: United States
facility: GSK Investigational Site
state: Illinois
city: North Dartmouth
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Neu-Ulm
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: