| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Adolescent (12-17 years) and Adult Asthmathics |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
| There are no secondary objectives. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 daily diary data. |
|
| E.4 | Principal 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 procedures.
20. Neurological or Psychiatric Disease or History of Drug or Alcohol Abuse which
in the opinion of the investigator could interfere with the subject’s proper completion
of the protocol requirements excludes study participation.
21. Tobacco Use: A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars, or pipe tobacco) or have historical use of 10 pack years or more (e.g. 20 cigarettes/day for 10 years).
22. 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.
23. Night Shift Work Schedule: A subject will not be eligible for this study if he/she worked the night shift during the week prioir to Visit 1, will work, or anicipates the possibility of working the night shift at any time during study participation.
24. Sleep Apnea: A subject is not eligible if he/she has clinically significant sleep apnea requiring the use of a continious positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device.
25. Insomnia: A subject is not eligible if he/she has chronic insomnia that has been diagnosed by polysomnography (PSG). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Twenty-four hour weighted mean serum cortisol. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Last patient's last visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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