A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Persistent Asthma.

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00398645

Collaborator

(none)

648

Enrollment

Locations

Arm

9.5

Duration (Months)

7.9

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: GW685698X 200mcg,GW685698X 200mcg and 400mcg	Phase 2

Detailed Description

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of GW685698X 200mcg Twice Daily, GW685698X 200mcg and 400mcg Once Daily in the Morning, and GW685698X 200mcg and 400mcg Once Daily in the Evening Compared with Placebo for 8 Weeks in Adolescent and Adult Subjects (12 Years of Age and Older) with Persistent Asthma.

Study Design

Study Type:

Interventional

Actual Enrollment :

648 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of GW685698X 200 mcg Twice Daily, GW685698X 200 mcg and 400 mcg Once Daily in the Morning, and GW685698X 200 mcg and 400 mcg Once Daily in the Evening Compared With Placebo for 8 Weeks in Adolescent and Adult Subjects (12 Years of Age and Older) With Persistent Asthma

Study Start Date :

Nov 15, 2006

Actual Primary Completion Date :

Aug 1, 2007

Actual Study Completion Date :

Aug 30, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1	Drug: GW685698X 200mcg,GW685698X 200mcg and 400mcg Other Names: GW685698X 200mcg GW685698X 200mcg and 400mcg

Arm

Intervention/Treatment

Experimental: Arm 1

Drug: GW685698X 200mcg,GW685698X 200mcg and 400mcg

Other Names:

GW685698X 200mcg

GW685698X 200mcg and 400mcg

Outcome Measures

Primary Outcome Measures

The primary efficacy measure will be mean change from baseline at Week 8 (last assessment on treatment using last observation carried forward) in tough (AM or PM pre-dose and pre-rescue bronchodilator) forced expiratory volume in one second (FEV1) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Type of Subject: Outpatient
Age: 12 years of age or older at Visit 1 (or ³18 years of age or older if local regulations or the regulatory status of study medication permit enrollment of adults only).
Gender: Male or eligible female - Females are eligible to participate only if they are currently non-pregnant and non-lactating. 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), Any intrauterine device (IUD) with a documented failure rate of less than 1% per year, Double-barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm), The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds), Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all subjects at all visits, Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all subjects at all visits, Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all subjects at all visits, Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days),
Asthma Diagnosis: Asthma as defined by the National Institutes of Health [National Institutes of Health, 2002; GINA, 2005].
Severity of Disease: A best AM FEV1 of 50% to 80% of the predicted value during Visit 1 based on the "Standardization of Lung Function Tests" [European Respiratory Society, 1993] standards for 18 years and older or Polgar [Polgar, 1971] standards for 12 to 17 years and race adjusted for African-Americans [American Thoracic Society, 1991].
Reversibility of Disease: Demonstrated ³12% and 200mL reversibility of FEV1 within 30 minutes following 200 to 400mcg of albuterol/salbutamol inhalation aerosol (or one nebulized albuterol/salbutamol treatment) at Visit 1. If a subject fails to demonstrate an increase in FEV1 of ³12% and 200mL, the subject is not eligible for the study and will not be allowed to re-screen.
Concurrent Anti-Asthma Therapy: Subjects must be using an inhaled corticosteroid for at least 3 months prior to Visit 1 and be maintained on a stable dose for four weeks prior to Visit 1 at one of the following doses: Anti-Asthma Therapy Maximum Daily Dose (mcg/day) Fluticasone propionate MDI CFC/HFA ≤220mcg1/≥250mcg2 Fluticasone propionate DPI 200mcg Beclomethasone dipropionate 420mcg1/500mcg2 Beclomethasone dipropionate HFA 160mcg1/200mcg2 Budesonide DPI 400mcg Flunisolide 1000mcg Triamcinolone acetonide 1000mcg Mometasone furoate 200mcg Ciclesonide 160mcg1/200mcg2

Ex-actuator dose: dose delivered to the lungs
Ex-valve dose: dose expressed from the valve

Short-Acting Beta2-Agonist: All subjects must be able to replace short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as-needed for the duration of the study. Subjects must be able to withhold all inhaled short-acting beta-sympathomimetic bronchodilators for at least 6 hours prior to study visits.Note: Nebulized albuterol/salbutamol will not be allowed during the study with the exception of its use during reversibility testing at Visit 1. The use of albuterol/salbutamol through the DISKUS/ACCUHALER device will not be allowed during the study.
Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.
Compliance: Subjects must be able to comply with all the study requirements.

Exclusion criteria:

History of Life-Threatening Asthma: History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures.
Anti-Asthma Medications: Asthma medications listed below must not have been used prior to Visit 1 for the required interval listed below, and not taken during the study: Within 24 hours of Visit 1: Oral short-acting beta2-agonists: Within 2 weeks of Visit 1:Combination therapy containing inhaled beta2-agonists and ICS for asthma (e.g., fluticasone propionate/salmeterol combination, budesonide/formoterol combination);Slow-release bronchodilators (e.g., aminophylline, theophylline);Anticholinergics; Long-acting beta2-agonists (e.g., salmeterol); Ketotifen; Nedocromil sodium; Sodium cromoglycate; Oral long-acting beta2-agonists. Within 4 weeks of Visit 1: Anti-leukotrienes including suppressors of leukotriene production and antagonists. Within 12 weeks of Visit 1: Systemic, oral, parenteral, or depot corticosteroids; Anti-IgE (e.g., omalizumab).
Other Medications: The medications listed below must not have been used prior to Visit 1 for the required interval indicated below, and not taken during the study: Within 4 weeks of Visit 1: Known potent inhibitors of CYP3A4 (e.g., ritonavir, ketoconazole)
Respiratory Infection: History of a respiratory tract infection within 4 weeks of Visit 1. In addition, the subject must be excluded, if such infection occurs between Visits 1 and 2.
Asthma Exacerbation: History of a an asthma exacerbation within 4 weeks of Visit 1, any asthma exacerbation requiring oral corticosteroids within 3 months of Visit 1, or any hospitalization due to asthma exacerbation within 6 months of Visit 1.
Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 1 or within ten half-lives (t1/2) of the prior investigational study (which ever is longer of the two) or concurrently during the study.
Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease including, but not limited to: cardiovascular disease, malignancy, 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.
Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has evidence of oropharyngeal candidiasis at Visit 1.
Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy.
Milk Protein Allergy: History of severe milk protein allergy.
Immunosuppressive Medications: A subject must not be using, or require use of, immunosuppressive medications during the study.

Note: Immunotherapy for the treatment of allergies is allowed during the study provided that it was initiated prior to Visit 1 and the subject is maintained on a stable daily dose throughout the study period.

Attendance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol or scheduled visits to the study center and compliance with study medication or procedures (e.g., 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 excludes study participation.
Tobacco Use: A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco) and must not have historical use of >10 pack years (e.g., 20 cigarettes/day for 10 years).
Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Fullerton	California	United States	92835
2	GSK Investigational Site	Huntington Beach	California	United States	92647
3	GSK Investigational Site	Orange	California	United States	92868
4	GSK Investigational Site	San Diego	California	United States	92123
5	GSK Investigational Site	Miami	Florida	United States	33143
6	GSK Investigational Site	North Dartmouth	Massachusetts	United States	02747
7	GSK Investigational Site	Saint Louis	Missouri	United States	63141
8	GSK Investigational Site	Dayton	Ohio	United States	45406
9	GSK Investigational Site	Sylvania	Ohio	United States	43560
10	GSK Investigational Site	Lake Oswego	Oregon	United States	97035
11	GSK Investigational Site	Medford	Oregon	United States	97504
12	GSK Investigational Site	Portland	Oregon	United States	97213
13	GSK Investigational Site	El Paso	Texas	United States	79925
14	GSK Investigational Site	San Antonio	Texas	United States	78229
15	GSK Investigational Site	South Burlington	Vermont	United States	05403
16	GSK Investigational Site	Greenfield	Wisconsin	United States	53228
17	GSK Investigational Site	Camperdown	New South Wales	Australia	2050
18	GSK Investigational Site	Concord	New South Wales	Australia	2139
19	GSK Investigational Site	Adelaide	South Australia	Australia	5000
20	GSK Investigational Site	Toorak Gardens	South Australia	Australia	5065
21	GSK Investigational Site	Clayton	Victoria	Australia	3168
22	GSK Investigational Site	Geelong	Victoria	Australia	3220
23	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
24	GSK Investigational Site	Ruse		Bulgaria	7000
25	GSK Investigational Site	Sofia		Bulgaria	1431
26	GSK Investigational Site	Sofia		Bulgaria	1606
27	GSK Investigational Site	Varna		Bulgaria	9010
28	GSK Investigational Site	Veliko Tarnovo		Bulgaria	5000
29	GSK Investigational Site	Bay Roberts	Newfoundland and Labrador	Canada	A0A 1G0
30	GSK Investigational Site	Brampton	Ontario	Canada	L6T 3T1
31	GSK Investigational Site	Woodstock	Ontario	Canada	N4S 4G3
32	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago	Chile	8207257
33	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	7500551
34	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	7500691
35	GSK Investigational Site	Valparaiso	Valparaíso	Chile	2341131
36	GSK Investigational Site	Split		Croatia	21000
37	GSK Investigational Site	Zagreb		Croatia	10000
38	GSK Investigational Site	Kassel	Hessen	Germany	34117
39	GSK Investigational Site	Marburg	Hessen	Germany	35037
40	GSK Investigational Site	Berlin		Germany	10367
41	GSK Investigational Site	Berlin		Germany	10717
42	GSK Investigational Site	Berlin		Germany	13597
43	GSK Investigational Site	Ashkelon		Israel	78360
44	GSK Investigational Site	Jerusalem		Israel	91120
45	GSK Investigational Site	Petach-Tikva		Israel	49100
46	GSK Investigational Site	Rehovot		Israel	76100
47	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44340
48	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64020
49	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64460
50	GSK Investigational Site	Mexico		Mexico	04530
51	GSK Investigational Site	Mexico		Mexico	6720
52	GSK Investigational Site	Tauranga		New Zealand	3001
53	GSK Investigational Site	Wellington		New Zealand	6035
54	GSK Investigational Site	San Isidro	Lima	Peru	Lima 27
55	GSK Investigational Site	Lima		Peru	Lima 1
56	GSK Investigational Site	Lima		Peru	Lima 27
57	GSK Investigational Site	Cebu		Philippines	6000
58	GSK Investigational Site	Manila		Philippines	1000
59	GSK Investigational Site	Quezon City		Philippines	1101
60	GSK Investigational Site	Barnaul		Russian Federation	656 045
61	GSK Investigational Site	Ekaterinburg		Russian Federation	620109
62	GSK Investigational Site	Irkutsk		Russian Federation	664005
63	GSK Investigational Site	Kazan		Russian Federation	420015
64	GSK Investigational Site	Moscow		Russian Federation	115 280
65	GSK Investigational Site	Moscow		Russian Federation	115478
66	GSK Investigational Site	St. Petersburg		Russian Federation	197022
67	GSK Investigational Site	Tomsk		Russian Federation	634 050
68	GSK Investigational Site	Amanzimtoti		South Africa	4126
69	GSK Investigational Site	Bellville		South Africa	7530
70	GSK Investigational Site	Bloemfontein		South Africa	9300
71	GSK Investigational Site	Cape Town		South Africa	7925
72	GSK Investigational Site	Newtown		South Africa	2113
73	GSK Investigational Site	Bangkok		Thailand	10330
74	GSK Investigational Site	Bangkok		Thailand	10400
75	GSK Investigational Site	Khon Kaen		Thailand	40002
76	GSK Investigational Site	Donetsk		Ukraine	83099
77	GSK Investigational Site	Kiev		Ukraine	01004
78	GSK Investigational Site	Kiev		Ukraine	01601
79	GSK Investigational Site	Kiev		Ukraine	03680
80	GSK Investigational Site	Kyiv		Ukraine	02091
81	GSK Investigational Site	Kyiv		Ukraine	03038
82	GSK Investigational Site	Vinnitsa		Ukraine	21021