Efficacy/Safety Study of Fluticasone Furoate/Vilanterol Combination and Fluticasone Furoate in Adult and Adolescent Asthmatics
- Conditions
- AsthmaMedDRA version: 14.1Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2012-002797-32-PL
- Lead Sponsor
- GlaxoSmithKline Research and Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 990
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.Informed consent: Subjects must give their signed and dated (written) informed consent to participate.
Written informed consent must be obtained if a subject’s current medication is changed as a result of study participation (e.g., withholding of albuterol for FEV1 measurements or withholding of LABA on the day of Visit 1) and the subject will be required to return to the clinic to complete the screening visit once the required wash-out has been completed.
2.Type of Subject: Subjects must be outpatients =12 years of age at Visit 1 who have had a diagnosis of asthma, as defined by the National Institutes of Health, for at least 12 weeks prior to Visit 1. Countries with local restrictions prohibiting enrolment of adolescents will only enroll subjects =18 years of age.
3.Gender: Subjects may be male or an eligible female.
Eligible female is defined as having non-childbearing potential or having childbearing potential and using an acceptable method of birth control consistently and correctly. The following is the GSK list of acceptable, highly effective methods for avoiding pregnancy with failure rates of less than 1% per year:
a.Abstinence from penile-vaginal intercourse, when this is the female’s preferred and usual lifestyle
b.Oral Contraceptive, either combined or progestogen alone
c.Injectable progestogen
d.Implants of etonogestrel or levonorgestrel
e.Estrogenic vaginal ring
f.Percutaneous contraceptive patches
g.Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label
h.Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, documented” refers to the outcome of the investigator's/designee’s medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject’s medical records.
i.Male condom combined with a female diaphragm either with or without a vaginal spermicide (foam, gel, film, cream, or suppository)
4.Severity of Disease: Subjects must have a best pre-bronchodilator FEV1 of 40%-80% of their predicted normal value.
Predicted values will be based upon NHANES III. The equations for the predicted values are:
•The Caucasian equation will be used unless the subject is of Hispanic or Latino, African-American, or Asian descent,
•If a subject is of Hispanic or Latino ethnicity, then the Mexican-American equations will be used irrespective of race.
•If a subject is of African-American/African race, then the African-American equations will be used.
•If a subject is of Asian race, then the Asian adjustment will be used.
5.Reversibility of Disease: Subjects must demonstrate =12% and =200mL reversibility of FEV1 within 10-40 minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (or an equivalent nebulized treatment with albuterol/salbutamol solution) or have documented reversibility testing within the 6 months prior to Visit 1 meeting this measure of reversibility. A spacer device may be used for testing, if required.
6.Asthma Therapy Prior to Visit 1:
Subjects are eligible if they have received ICS for at least 12 weeks prior to Visit 1 and their treatment during the
Subjects meeting any of the following criteria must not be enrolled in the study:
1.History of Life-threatening Asthma: Defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
2.Respiratory Infection: Culture documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is:
a.not resolved within 4 weeks of Visit 1 and led to a change in asthma management or,
b.in the opinion of the investigator, expected to affect the subject’s asthma status or the subject’s ability to participate in the study.
3.Asthma Exacerbation: Any asthma exacerbation that
a.required oral corticosteroids within the 12 weeks prior to Visit 1 or
b.resulted in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.
4.Concurrent Respiratory Disease: A subject must not have current evidence of
a.Atelectasis (segmental or larger)
b.Bronchopulmonary dysplasia
c.Chronic obstructive pulmonary disease including chronic bronchitis and emphysema
d.Pneumonia
e.Pneumothorax
f.Pulmonary fibrotic disease
g.Or any evidence of concurrent respiratory disease other than asthma
5.Other Concurrent Diseases/Abnormalities:A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
6.Viral Hepatitis: Subjects with chronic stable hepatitis B or C are acceptable provided their screening alanine transaminase (ALT) is <2x upper limit of normal (ULN) and the subject otherwise meets the entry criteria. Subjects who have chronic co-infection with both hepatitis B and hepatitis C are not eligible.
7.Oral Candidiasis: A subject will not be eligible if he/she has clinical visual evidence of candidiasis at Visit 1.
8.Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study, whichever is longer of the two.
9.Allergies:
a.Drug Allergy: Any adverse reaction, including immediate or delayed hypersensitivity, to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy or known or suspected sensitivity to the constituents of the NDPI (i.e., lactose or magnesium stearate)
b.Milk Protein Allergy: History of severe milk protein allergy
10.Concomitant Medication: Administration of prescription or non-prescription medication that would significantly affect the course of asthma, or interact with study drug, such as anticonvulsants (barbiturates, hydantoins, carbamazepine), polycyclic antidepressants, beta-adrenergic blocking agents, phenothiazines, and monoamine oxidase (MAO) inhibitors
11.Immunosuppressive Medications: A subject must not be using or require use of immunosuppressive medications during the study.
12.Cytochrome P450 3A4 (CYP3A4) Inhibitors: Subjects who have received a potent CYP3A4 inhibitor within 4 weeks of Visit 1 are ineligible. (See SPM for listing of strong CYP3A4 inhibitors).
13.Compliance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy and safety of once daily (evening) administration of FF/VI 100/25 with FF 100 in adult and adolescent subjects = 12 years of age with moderate to severe, persistent bronchial asthma over 12 weeks.;Secondary Objective: To assess the relative efficacy of Fluticasone Furoate/Vilanterol 200/25mcg and Fluticasone Furoate/Vilanterol 100/25.;Primary end point(s): Weighted mean serial FEV1 over 0-24 hours post-dose at the end of the 12 week treatment period.<br>;Timepoint(s) of evaluation of this end point: Pre-dose, post-dose assessments at 5, 15, and 30 minutes and at 1, 2, 3, 4, 5, 12, 16, 20, 23 and 24 hours.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Change from baseline in clinic visit trough FEV1 <br>•Change from baseline in the percentage of rescue-free 24-hour periods <br>•Change from baseline in the percentage of symptom-free 24-hour periods <br>•Change from baseline in AM PEF <br>•Change from baseline in PM PEF ;Timepoint(s) of evaluation of this end point: •Change from baseline in clinic visit trough FEV1: at the end of the 12 week treatment period<br>•Change from baseline in the percentage of rescue-free 24-hour periods: during the 12-week treatment period<br>•Change from baseline in the percentage of symptom-free 24-hour periods: during the 12-week treatment period<br>•Change from baseline in AM PEF: averaged over the 12-week treatment period<br>•Change from baseline in PM PEF: averaged over the 12-week treatment period<br>