A Randomized Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group, Multicenter, Dose Ranging Study to Evaluate the Efficacy and Safety of GW685698X Inhalation Powder Administered Once Daily and Fluticasone Propionate Inhalation Powder 100mcg Twice Daily Compared With Placebo for 8 Weeks in Adolescent and Adult Subjects With Persistent Asthma Symptomatic on Non-Steroidal, Asthma Therapy

GlaxoSmithKline1 site in 1 country599 target enrollmentDecember 1, 2007

ConditionsAsthma

InterventionsPlacebo GW685698X

DrugsGW685698X Placebo

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Asthma
Sponsor: GlaxoSmithKline
Enrollment: 599
Locations: 1
Primary Endpoint: Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Detailed Description

A Randomized Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group, Multicenter, Dose Ranging Study to Evaluate the Efficacy and Safety of GW685698X Inhalation Powder Once Daily and Fluticasone Propionate Inhalation Powder Twice Daily compared with Placebo for 8 Weeks in Adolescent and Adult Subjects with Persistent Asthma Symptomatic on Non-Steroidal, Asthma Therapy

Registry

clinicaltrials.gov

Start Date

December 1, 2007

End Date

October 2, 2008

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects eligible for enrollment in the study must meet all of the following criteria:
•Type of Subject: Outpatient
•Age: 12 years of age or older at Visit
•For sites in the following countries, subjects recruited will be ≥18 years of age: Bulgaria, Czech Republic, Germany, Greece, Lithuania, New Zealand, Russian Federation, Turkey and any other countries where local regulations or the regulatory status of study medication permit enrollment of adults only.
•Gender: Male or Eligible Female
•To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following:
•Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject
•Implants of levonorgestrel
•Injectable progestogen
•Oral contraceptive (either combined estrogen/progestin or progestin only)

Exclusion Criteria

•History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures.
•Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks before Visit 1 and 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.
•Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 3 months of Visit
•A subject must not have had any hospitalization for asthma within 6 months prior to Visit
•Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease including, but not limited to: cardiovascular disease, hepatic disease, renal disease, hematological disease, neurological disease, or pulmonary disease (including, but not confined to chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia, and chronic obstructive pulmonary disease). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. The list of additional excluded conditions/diseases includes, but is not limited to the following: congestive heart failure, clinically significant coronary heart disease, stroke within 3 months of Visit 1, poorly controlled peptic ulcer, immunologic compromise, tuberculosis (current or untreated), Addison's disease, uncontrolled thyroid disorder, known aortic aneurysm, clinically significant cardiac arrhythmia, uncontrolled hypertension1, hematological, hepatic, or renal disease, current malignancy2, cushings disease, uncontrolled diabetes mellitus, recent history of drug or alcohol abuse.
•systolic blood pressure ≥160, or diastolic blood pressure \>100
•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)
•Patients with a history of tuberculosis who have received an approved prophylactic treatment regimen or an approved active treatment regimen and who have had no evidence of active disease for a minimum of 2 years may be enrolled \[American Thoracic Society, 2003; American Thoracic Society, 2005\]"
•Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of oral candidiasis at Visit
•Investigational Medications: A subject must not have participated in a study or used any investigational drug within 30 days prior to Visit

Arms & Interventions

Placebo

Intervention: Placebo

GW685698X

Intervention: GW685698X

Outcomes

Primary Outcomes

Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8

Time Frame: Baseline and Week 8

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Pre-dose and pre-rescue bronchodilator (albuterol/salbutamol) trough FEV1(the measurement of FEV1 performed at the end of the dosing interval) was measured electronically by spirometry in the evening at the Baseline through Week 8 clinic visits. Trough FEV1 is the FEV1 measured approximately 24 hours after the last administration of study drug. The highest of 3 technically acceptable measurements was recorded. The Visit 3 FEV1 assessment was used as the Baseline value. Change from Baseline in trough FEV1 was calculated as the value at Week 8 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline trough FEV1, country, sex, age, and treatment group.

Secondary Outcomes

Mean Change From Baseline in Daily Trough (Pre-dose and Pre-rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Averaged Over the 8-week Treatment Period(From Baseline up to Week 8)
Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period(From Baseline up to Week 8)
Mean Change From Baseline in the Percentage of Symptom-free 24 Hour (hr) Periods During the 8-week Treatment Period(From Baseline up to Week 8)
Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis(From Baseline up to Week 8/Early Withdrawal)
Mean Change From Baseline in the Percentage of Rescue Free 24-hour (hr) Periods During the 8-week Treatment Period(From Baseline up to Week 8)
Number of Participants With Any On-treatment Adverse Events or Serious Adverse Events Throughout the 8-week Treatment Period(From the first dose of study medication up to Week 8/Early Withdrawal)
Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period(From the first dose of study medication up to Week 8/Early Withdrawal)
Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8(Baseline and Week 8)
Hematocrit at Baseline and Week 8(Baseline and Week 8)
Hemoglobin at Baseline and Week 8(Baseline and Week 8)
Platelet Count and White Blood Cell (WBC) Count at Baseline and Week 8(Baseline and Week 8)
Red Blood Cells (RBC) Count at Baseline and Week 8(Baseline and Week 8)
Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Lactate Dehydrogenase (LD), and Gamma Glutamyltransferase (GGT) at Baseline and Week 8(Baseline and Week 8)
Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8(Baseline and Week 8)
Clinical Chemistry Parameters of Chloride, Calcium, Carbon Dioxide Content/Bicarbonate (CO2/BI), Cholesterol, Glucose, Phosphorus Inorganic(PI), Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Baseline and Week 8(Baseline and Week 8)
Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8(Baseline and Week 8)
Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal(Baseline and Week 8/Early Withdrawal)
Urine Specific Gravity at Baseline and Week 8/Early Withdrawal(Baseline and Week 8/Early Withdrawal)
Urine pH at Baseline and Week 8/Early Withdrawal(Baseline and Week 8/Early Withdrawal)
24-hour Urinary Cortisol Excretion at Baseline and Week 8(Baseline and Week 8)
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 8(Baseline and Week 8)
Change From Baseline in Heart Rate at Week 8(Baseline and Week 8)