Clinical trial NCT00600171: Efficacy And Safety Of GW642444M Comparing Placebo In Adolescent And Adult Subjects With Persistent Asthma.
Official title: A Randomised, Double-blind, Placebo Controlled, Parallel Group, Dose Ranging Study Evaluating the Efficacy and Safety of GW642444M Administered Once Daily Compared With Placebo for 28 Days in Adolescent and Adult Subjects With Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: dose ranging
placebo
asthma
safety
efficacy
pharmacokinetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-01-24
Enrollment: 614
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to determine if the investigational drug is effective and safe in individuals with asthma


Eligibility criteria: Inclusion criteria:

* Aged 12 years of age or older at Visit 1 For sites in the following countries, subjects recruited will be ³ 18 years of age: Germany, Hungary and the Russian Federation and any other countries where local regulations or the regulatory status of study medication permit enrolment of adults only.
* Male or eligible female subjects

A female is eligible to enter and participate in the study if she is of:

Non-child bearing potential (i.e. physiologically incapable of becoming pregnant), including any female who is post-menopausal.

Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact):

* Complete abstinence from intercourse from screening until 2 weeks after the follow-up contact; or
* Sterilisation of male partner (vasectomy with documentation of azoospermia) prior to female subject entry into the study, and this male partner is the sole partner for that subject; or
* Implants of levonorgestral inserted for at least 1 month prior to the study medication administration but not beyond the third successive year following insertion; or
* Injectable progestogen administered for at least 1 month prior to study medication administration and administered for 1 month following study completion; or
* Oral contraceptive (combined or progestogen only) administered for at least one monthly cycle prior to study medication administration; or
* Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) N.B. For German sites female subjects must use a method of birth control other than the double barrier method
* An intrauterine device (IUD), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year; or
* Estrogenic vaginal ring inserted for at least 1 month prior to study medication administration; or
* Percutaneous contraceptive patches in place for at least 1 month prior to study medication administration Female subjects should not be enrolled if they are pregnant, or lactating, or plan to become pregnant during the time of study participation.
* Documented clinical history of persistent asthma, as defined by the National Institutes of Health \[NIH, 2007\] first diagnosed at least 6 months prior to Visit 1.
* Subjects with current reversible airways disease as demonstrated at Visit 1 by an increase in FEV1 of ≥ 12% and ≥ 200ml over the pre-salbutamol/albuterol FEV1 at approximately 30 minutes after the inhalation of 400mcg of salbutamol/albuterol via MDI (spacer permitted for reversibility testing only if required) or one nebulised salbutamol/albuterol solution.
* Subjects must be using an inhaled corticosteroid and have been maintained on a stable dose for 4 weeks prior to Visit 1 at one of the following doses:

Maximum Allowable Concurrent Inhaled Corticosteroid Doses

Asthma Therapy(Maximum Daily Dose (mcg/day)) fluticasone propionate MDI CFC/HFA (≤ 880mcg1/ ≤1000mcg2) fluticasone propionate DPI(≤ 1000mcg) beclomethasone dipropionate(≤ 1680mcg1/ ≤ 2000mcg2) beclomethasone dipropionate HFA (QVAR)(≤ 640mcg1/ ≤ 800mcg2) budesonide DPI/MDI(≤ 2000mcg) Flunisolide(≤ 2000mcg) triamcinolone acetonide(≤ 2000mcg) mometasone furoate(≤ 880mcg) Ciclesonide(≤ 320mcg1/ ≤ 400mcg2)

CFC=chlorofluorocarbon HFA=hydrofluoroalkane

1. Ex-actuator dose
2. Ex-valve dose

   * Pre-bronchodilator FEV1 between ≥ 40 - ≤ 90% predicted at Visit 1. NHANES III predicted values will be used for subjects aged ≥ 12 years and adjustments to predicted values will be made for African American subjects \[Hankinson, 1999\].
   * Appropriately signed and dated informed consent has been obtained.
   * Capable of withholding salbutamol/albuterol use for ≥ 6 hours prior to clinic visits.
   * In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion criteria:

* An exacerbation of asthma within 4 weeks of Visit 1, or a culture documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear within 4 weeks of Visit 1 that led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subjects asthma status or the subjects ability to participate in the study.
* History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest or hypoxia seizures.
* Asthma exacerbation requiring treatment with oral corticosteroids within 3 months prior to Visit 1.
* Hospitalised for an asthma exacerbation within 6 months of Visit 1. Hospitalisation is defined as an overnight stay in a hospital.
* Previously enrolled in this study, or has participated in any study using an investigational drug during the previous 30 days or will participate simultaneously in another clinical trial.
* A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the subject's safety at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.

The list of additional excluded conditions/diseases includes, but is not limited to the following:

congestive heart failure, known aortic aneurysm clinically significant coronary heart disease, clinically significant cardiac arrhythmia stroke within 3 months of Visit 1, uncontrolled hypertension1 poorly controlled peptic ulcer, haematologic, hepatic, or renal disease immunologic compromise, current malignancy2 tuberculosis (current or untreated3), Cushing's disease Addison's disease, uncontrolled diabetes mellitus uncontrolled thyroid disorder, recent history of drug or alcohol abuse neurological disease, pulmonary disease4

1. systolic blood pressure 160, or diastolic blood pressure \>100
2. history of malignancy is acceptable only if subject has been in remission for one year prior to Visit 1 (remission = no current evidence of malignancy and no treatment for the malignancy in the 12 months prior to Visit 1)
3. Subjects with a history of tuberculosis who have received an approved prophylactic treatment regimen or an approved active treatment regimen and who have no evidence of active disease for a minimum of 2 years may be enrolled \[American Thoracic Society Documents, 2005\] \[American Thoracic Society (ATS), 2003\]
4. Including but not limited to chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia, and chronic obstructive pulmonary disease.

   * Any adverse reaction including immediate or delayed hypersensitivity to any ß2-agonist or sympathomimetic drug, or known (i.e., patients with a history of severe milk protein allergy) or suspected sensitivity to the constituents of GW642444M inhalation powder (e.g., lactose or magnesium stearate).
   * Subjects who are likely to be non-compliant with study medication and other study-related requirements (e.g. attendance at clinic visits or completion of Daily Diary).
   * Neurological or psychiatric disease or history of drug or alcohol abuse which would interfere with the subject's proper completion of the protocol requirements.

Abuse of alcohol is defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). The number of units of alcohol in a drink can be determined by multiplying the volume of the drink (in millilitres) by its percentage ABV and dividing by 1000

* Current smoker or a smoking history of 10 pack years or more (e.g. 20 cigarettes/day for 10 years). A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco).
* Administration of systemic, oral or depot corticosteroids or administration of anti-IgE (e.g. omalizumab \[Xolair\]) within 12 weeks of Visit 1.
* Administration of the following asthma medications within 14 days of Visit 1:
* Theophyllines
* Oral β2-agonists (e.g. bambuterol)
* Slow-release bronchodilators
* Anticholinergics - short or long-acting
* Oral long acting antihistamines
* Oral leukotriene receptor antagonists (e.g. montelukast)

Primary outcomes:
measure: Mean Change From Baseline in Clinic Visit Trough FEV1 at Day 28 (Last Observation Carried Forward [LOCF])
timeFrame: Baseline and Day 28
Secondary outcomes:
measure: Mean Change From Baseline in Clinic Visit Trough FEV1 at Day 28 Per Stratum (LOCF)
timeFrame: Baseline and Day 28
measure: Change From Baseline in Weighted Mean 24-hour Serial FEV1 at Day 1 and Day 28
timeFrame: Baseline; Day 1 and Day 28 (mean post-dose FEV1 after 15, 30, and 60 minutes and 2, 3, 4, 6, 12, 16, 20, 22, 23, and 24 hours)
measure: Mean Change From Baseline in Trough (Pre-dose and Pre-bronchodilator) Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 28-day Treatment Period
timeFrame: Baseline and Days 1-28
measure: Mean Change From Baseline in Daily Morning (AM) PEF Averaged Over the 28-day Treatment Period
timeFrame: Baseline and Days 1-28
measure: Mean Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Averaged Over the 28-day Treatment Period
timeFrame: Baseline and Days 1-28
measure: Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods Averaged Over the 28-day Treatment Period
timeFrame: Baseline and Days 1-28
measure: Difference in Post Salbutamol/Albuterol FEV1 (FEV1 30 Minutes After a Single Dose of 400 µg Salbutamol/Albuterol) Between the Following Time Points: 24 Hours After Dosing on Day 1 and Day 28
timeFrame: 24 hours after dosing on Day 1 (Visit 2) and on Day 28 (Visit 5)
measure: Difference in Post Salbutamol/Albuterol FEV1 (FEV1 30minutes After a Single Dose of 400 µg Salbutamol/Albuterol) Between the Following Time Points: Screening and 24 Hours After Dosing on Day 1
timeFrame: Screening (Visit 1) and 24 hours after dosing on Day 1 (Visit 2)
measure: Difference in Post Salbutamol/Albuterol FEV1 (FEV1 30 Minutes After a Single Dose of 400 µg Salbutamol/Albuterol) Between the Following Time Points: Screening and 24 Hours After Dosing on Day 28
timeFrame: Screening (Visit 1) and 24 hours after dosing on Day 28 (Visit 5)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Huntington Beach
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Tallahassee
country: United States
facility: GSK Investigational Site
state: Florida
city: Valrico
country: United States
facility: GSK Investigational Site
state: Florida
city: Coeur D'Alene
country: United States
facility: GSK Investigational Site
state: Idaho
city: River Forest
country: United States
facility: GSK Investigational Site
state: Illinois
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Sunset
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Bethesda
country: United States
facility: GSK Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Columbia
country: United States
facility: GSK Investigational Site
state: Missouri
city: Rolla
country: United States
facility: GSK Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Skillman
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Canton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Providence
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Orangeburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: La Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Tucuman
country: Argentina
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sainte-Foy
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Trois Rivières
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Montpellier
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Toulouse cedex 9
country: France
facility: GSK Investigational Site
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Wiesloch
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ruedersdorf
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Geesthacht
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Cheongju, Chungcheongbuk-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon-Si
country: Korea, Republic of
facility: GSK Investigational Site
city: Harderwijk
country: Netherlands
facility: GSK Investigational Site
city: Heerlen
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
city: Cavite
country: Philippines
facility: GSK Investigational Site
city: Manila
country: Philippines
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Kazan
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Ryazan
country: Russian Federation
facility: GSK Investigational Site
city: Saratov
country: Russian Federation
facility: GSK Investigational Site
city: St.Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Amanzimtoti
country: South Africa
facility: GSK Investigational Site
city: Cape Town
country: South Africa
facility: GSK Investigational Site
city: Claremont
country: South Africa
facility: GSK Investigational Site
city: Mowbray
country: South Africa
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
city: Chiangmai
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Lotvall J, Bateman ED, Bleecker ER, Busse WW, Woodcock A, Follows R, Lim J, Stone S, Jacques L, Haumann B. 24-h duration of the novel LABA vilanterol trifenatate in asthma patients treated with inhaled corticosteroids. Eur Respir J. 2012 Sep;40(3):570-9. doi: 10.1183/09031936.00121411. Epub 2012 Feb 23.