A study of the Effects of Inhaled Fliticasone Furotate/GW642444 versus Placebo on HPA Axis of Adolescent and Adult Asthmatics.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-017669-44-PL
• Date of registration: 22/02/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A study of the Effects of Inhaled Fliticasone Furotate/GW642444 versus Placebo on HPA Axis of Adolescent and Adult Asthmatics.
• Scientific title: A study of the Effects of Inhaled Fliticasone Furotate/GW642444 versus Placebo on HPA Axis of Adolescent and Adult Asthmatics.
• Date of first enrolment: 04/05/2010
• Target sample size: 185
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017669-44
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Germany, Poland

Key inclusion & exclusion criteria

Inclusion criteria:
1. Type of Subject: Outpatient and able to complete two overnight domiciled clinic
stays.

2. Age =18 to =65.

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
• 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 and 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 <8 mg/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 and willing to give written informed
consent to take part in the study.

9. Compliance: Subjects must be judged by the investigator as able to comply with
study procedures and completion of the d
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 protiocol for further information
4. Asthma Exacerbation: Any asthma exacerbation requiring systemic corticosteroids
within 12weeks 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 prohibitedd 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 for the duration of 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 aspect
of this study protocol, scheduled visits to the study center, non-compliance with
investigational product, or procedu

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Adolescent (12-17 years) and Adult Asthmathics
MedDRA version: 12.1 Level: LLT Classification code 10003553 Term: Asthma

Intervention(s)

Product Name: Fluticasone furotate/GW642444 Inhalation Powder
Product Code: Fluticasone furotate/GW642444
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: GW685698 (Fluticasone furotate)
CAS Number: 397864-44-7
Current Sponsor code: GWX685698X
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: GW642444M
CAS Number: 503070-58-4
Current Sponsor code: GW642444
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Product Name: Fluticasone furotate/GW642444 Inhalation Powder
Product Code: Fluticasone furotate/GW642444
Pharmaceutical Form: Inhalation powder, pre-dispensed
INN or Proposed INN: GW685698 (Fluticasone furotate)
CAS Number: 397864-44-7
Current Sponsor code: GW685698X
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: GW642444M
CAS Number: 503070-58-4
Current Sponsor code: GW642444
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Inhalation powder, pre-dispensed
Route of administration of the placebo: Inhalation use

Trade Name: Prednisolone
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolonum
CAS Number: 8056-11-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to assess the effect of six weeks’ treatment with two once-daily strengths of Fluticasone Fuorate /GW642444 Inhalation Powder on the hypothalamic-pituitary-adrenal (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.

Primary end point(s): Twenty-four hour weighted mean serum cortisol.

Secondary Objective: There are no secondary objectives.

Secondary ID(s)

2009-017669-44-DE

HZA106851