| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003555 |
|
| 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 aim of the study is to demonstrate the therapeutic equivalence of generic formulations of fluticasone propionate, 125 or 250 µg twice daily administered from pMDI (Merck Generics) with reference fluticasone propionate formulations, 125 or 250 µg twice daily administered from reference pMDI in adult patients with mild to moderate persistent asthma who are inhaled corticosteroid naïve or symptomatic despite being on low dose inhaled corticosteroid therapy. |
|
| E.2.2 | Secondary objectives of the trial |
| The secondary aim of the study is to evaluate safety and tolerability of the generic formulations in comparison with the reference formulations in terms of vital signs, routine haematology and biochemistry, 24-hour urinary free cortisol levels (expressed as cortisol:creatinine ratio), physical examination and adverse events (including oral candidiasis). |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
Patients will be eligible for enrolment into the study if all of the following criteria are met at the screening visit (Visit 1):
1. Male and female patients aged 18 to 65 years (inclusive)
2. Documented clinical history of reversible obstructive airways disease of at least 6 months duration at the time of the Visit 1 for patients already receiving a low dose of ICS (including documented evidence of a clinical improvement on treatment with anti-asthma medication, e.g. improvements in symptoms or lung function)
OR
Documented clinical history of reversible obstructive airways disease of at least 2 weeks duration at the time of the Visit 1 for patients who are ICS naïve
3. Patients who are ICS naïve OR on current treatment with low dose ICS (≤ 400 µg/daily budesonide equivalent) for at least 4 weeks prior to Visit 1 (see appendix 2 of protocol for equivalent doses for other ICS)
4. Female patients of childbearing potential must agree to use adequate contraception during their participation in the study and for a period of 4 weeks following their final administration of study treatments (acceptable methods of contraception include hormonal contraception (either in a depot or oral formulation at a stable dose for at least 3 months prior to the start of the treatment) or a barrier method (intrauterine device, diaphragm, combination of condom and spermicide) or an agreement to avoid becoming pregnant). A female of non-childbearing potential will be defined as one who has been postmenopausal for at least 24 months, has been surgically sterilised (i.e. tubal ligation) or had a hysterectomy prior to screening.
5. Ability to correctly use the pMDI, with the aid of a spacer if necessary (however, the use/non-use of a spacer device must remain constant throughout the patient’s participation in the study)
6. The patient’s written informed consent to participate in the study
The following must be demonstrated after withholding use of short-acting β2-agonists for the preceding 4 hrs. If a patient fails to meet the washout criteria at the screening visit, another appointment should be made to obtain clinical spirometry data:
7. FEV1 between 60% and 85% of the predicted value for their age, height and gender at screening, (refer to section 5.8.3.1.2 of protocol)
Note: Patients must not enter the run-in period without meeting this criterion
8. Reversibility: demonstrated by a ≥ 12% increase in FEV1 (with an absolute improvement in FEV1 of at least 200mL) ≥ 10 min and up to 15 minutes after inhalation of up to 400 µg salbutamol (Ventolin Evohaler®) via a spacer (refer to section 5.8.3.1.2 of protocol)
Note: Patients with a study-qualifying FEV1 may enter the run-in period without having demonstrated reversibility. Reversibility can be determined at screening, during the run-in period or at the randomisation visit. At the investigator’s discretion, if a patient fails to meet the ≥ 12% threshold, the reversibility tests may be repeated as many times as necessary during this period. Once reversibility has been demonstrated the reversibility test should not be repeated. |
|
| E.4 | Principal exclusion criteria |
Patients will be excluded from participation if any of the following apply at screening (Visit 1):
1. Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical evaluation
2. Concomitant severe diseases or diseases which the investigator believes are contraindications for the use of inhaled steroids or which may affect the study outcome measures (e.g. active pulmonary tuberculosis)
3. Suffering from chronic obstructive pulmonary disease (i.e. chronic bronchitis or emphysema) and/or other relevant lung diseases causing variable impairment in lung function
4. Hospitalisation for asthma in the 6 months preceding Visit 1
5. Current or recent (within 3 months of Visit 1) systemic (oral, parenteral or depot) corticosteroid therapy or receipt of more than 3 short courses of systemic corticosteroid therapy in the preceding year
6. Current or recent (within 3 months of Visit 1) use of long-acting β2-agonists (inhaled, oral or otherwise systemic)
7. Current use of anticholinergics for the relief of asthma symptoms
8. Asthma exacerbations or respiratory tract infection requiring antibiotic treatment during the past 6 weeks
9. Known or suspected hypersensitivity to fluticasone or the excipients of either of the pMDIs
10. Inability to perform lung functions tests
11. Patients who are unlikely to be compliant, take their medication as directed, complete the diary and daily lung testing procedures or attend scheduled clinic visits.
12. Evidence of current neoplastic or systemic disease or diagnosed tuberculosis
13. Pregnant or lactating women
14. Smokers (current or previous) with > 10 pack years
15. Evidence of history of alcohol or drug abuse
16. Participation in an investigational drug trial during 30 days preceding Visit 1
17. Employees of Merck Generics or Omnicare Clinical Research Ltd. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary efficacy measure is morning peak expiratory flow rate (PEFR) recorded daily with the Vitalograph® 2110 PEF FEV Diary.
The primary efficacy variable is defined as the mean change in morning PEFR from baseline, where the baseline value is defined as the average of the last 7 days of the run-in period (with day 7 being the day before the randomisation visit). All post- randomisation measurements will be used for calculating the post-baseline average. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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
|
| End of the trial is the last visit of the last subject |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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