Study HZA106851: A Study of the Effects of Inhaled Fluticasone Furoate/GW642444 versus Placebo on the HPA Axis of Adolescent and Adult Asthmatics

• Conditions: Asthma; MedDRA version: 12.1Level: LLTClassification code 10003553Term: Asthma

• Registration Number: EUCTR2009-017669-44-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-22
• Last Update Posted: 1 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 185

Inclusion Criteria

1. Type of Subject: Outpatient and able to complete two overnight domiciled clinic stays.
2.Age: =12 to =65 years of age (or =18 to =65 years of age if local regulations or the regulatory status of study medication permit enrolment of adults only). In Germany: =18 to =65 years.
3. 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 or etonogestrel
• Injectable progestogen
• Oral contraceptive (either combined estrogen/progestin or progestin only)
• Estrogenic vaginal ring
• Percutaneous contraceptive patches
• Any intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year.
• Double barrier method – condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
• Abstinence: 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).
Female subjects should not be enrolled if they are pregnant, lactating, or plan to become pregnant during the time of study participation. A serum pregnancy test will be required on all females of childbearing potential at Visit 1.
4. Asthma Diagnosis: A history of asthma as defined by the National Institutes of Health [NIH, 2007] for at least 12 weeks prior to Visit 1.
5. Severity of Disease: A best FEV1 of =50% of the predicted normal value during the Visit 1 screening visit. Predicted values will be based upon NHANES III. [Hankinson, 1999]. Note: If a subject is recorded as having Hispanic or Latino ethnicity then the Mexican-American equations will be used (irrespective of race). If a subject is recorded as being of African American/African heritage race, then the African-American equations will be used. Otherwise, the Caucasian equations will be used.
6. Reversibility of Disease: Demonstrated a = 12% and =200mL reversibility of FEV1 within approximately 10 to 40 minutes following 2 to 4 inhalations of albuterol/salbutamol inhalation aerosol (if required, spacers are permitted for reversibility testing only) or one nebulized albuterol/salbutamol solution during the screening period or historical documentation of same FEV1 reversibility within 12 months prior to screening or a positive methacholine challenge test within 12 months prior to screening. A positive response to a methacholine challenge is defined as a 20% decrease in response to methacholine (PC20) of <8mg/ml.
7. Short-acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as needed for the duration of the study. The use of spacer devices with metered dose inhaler (MDI) or nebulized albuterol/salbutamol will not be allowed during the study with the exception of their use during reversibility testing at Visit 1. Subjects must be able to withhold all inhaled short-acting beta sympathomimetic bronchodilators for at least 6 hours prior to study visits.
8. Informed Consent: All subjects must be able an

Exclusion Criteria

1. History of Life-threatening Asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within 5 years prior to Visit 1.
2. Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
3. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear – view protocol for further information.
4. Asthma Exacerbation: Any asthma exacerbation requiring systemic corticosteroids within 12 weeks of Visit 1. A subject must not have had any overnight hospitalization for asthma within 6 months prior to Visit 1.
5. Concurrent Diseases/Abnormalities: Other Concurrent Diseases/Abnormalities: A subject must not have any clinically significant, uncontrolled condition or disease - view protocol for further information.
6. Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of oral candidiasis at Visit 1.
7. Investigational Medications: Use of any investigational drug within 30 days prior to Visit 1
8. Previous Study Participation: A subject may not have previously been randomized to treatment in a Phase III fluticasone furoate/GW642444 combination product study (i.e., HZA106825, HZA106827, HZA106829, HZA106837, HZA106839, HZA113091).
9. Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy view protocol for further information.
10. Milk Protein Allergy: History of severe milk protein allergy
11. Immunosuppressive Medications: A subject must not be using or require use of immunosuppressive medications during the study.
12. Concomitant Medications: Use of prescription or over-the-counter medications that would significantly affect the course of asthma, view protocol for further information.
13. Systemic/Oral/Depot Corticosteroid: Administration of systemic, oral, or depot corticosteroids within 12 weeks prior to Visit 1 and during the study is prohibited.
14. Inhaled Corticosteroid Use: Use of an inhaled corticosteroid during the 4 weeks prior to Visit 1 and during the study is prohibited.
15. Intranasal Corticosteroids: Use is prohibited starting one day prior to Visit 1 and during the study.
16. Potent Cytochrome P450 3A4 (CYP3A4) inhibitors: A subject is not eligible if he/she is receiving potent CYP34A inhibitor within 4 weeks of Visit 1 and during the study (e.g., ritonavir, ketoconazole, itraconzole).
17. Long-acting beta2-agonists: Use is prohibited for 4 weeks prior to Visit 1 and during the study.
18. Extended-release short-acting beta2-agonists: Use is prohibited for the period of the prescribed dosing interval prior to the screening visit and for the duration of the study.
18.Intranasal Corticosteroids: Use is prohibited starting one day prior to Visit 1 and during the study.
19. Attendance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, or resides in a geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspe

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to assess the effect of six weeks’ treatment with two once-daily dosing regimens of FF/GW642444 Inhalation Powder on the HPA axis system compared with placebo. A 7-day course of oral prednisolone is included as an active control to ensure the assay is sufficiently sensitive to detect a drug effect. ;Secondary Objective: None;Primary end point(s): Twenty-four hour weighted mean serum cortisol