| 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 | 12.0 |
| 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 |
To assess the bronchodilator effect of an orally inhaled indacaterol maleate PulmoSphere® formulation in patients with persistent asthma compared with placebo as measured by mean change in FEV1 from baseline to post-dose trough following single dose treatment. Trough is defined as the mean of FEV1
at 23 h 10 min and 23 h 45 min post-dose. |
|
| E.2.2 | Secondary objectives of the trial |
- To assess bronchodilator effect of an orally inhaled indacaterol maleate PulmoSphere® formulation in patients with persistent asthma compared with placebo as measured by other lung funtion measures
- To assess safety & tolerability of orally inhaled indacaterol maleate PulmoSphere® formulation in comparison to placebo in terms of number & percentage of adverse events, laboratory analysis, vital signs & ECGs.
- To evaluate effect of indacaterol maleate PulmoSphere® formulation administered via Simoon device on absorption & systemic exposure of indacaterol as compared with indacaterol maleate administered via concept1 device.
- To evaluate the incidence, duration and severity of post-inhalational cough after oral inhalation of indacaterol maleate PulmoSphere® formulation administered via the Simoon device in comparison to Concept1 device.
- To obtain patient feedback on the use & convenience of Simoon device.
- To assess the mechanical performance of Simoon device |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female adult patients aged 18-75 years (inclusive), who have signed an Informed Consent Form prior to initiation of any study-related procedure, including any adjustments to asthma medication prior to screening.
2. Patients with persistent asthma, diagnosed according to GINA guidelines (National
Institute of Health, National Heart, Lung and Blood Institute, 2008) and who additionally meet the following criteria:
a. Patients receiving daily treatment with inhaled corticosteroid up to the maximum dose per day indicated in the package leaflet, in a stable regimen for the month prior to screening.
b. Patients with an FEV1 at screening of ≥50% of the predicted normal value for the patient. This criterion for FEV1 will have to be demonstrated after a washout period of at least 6 hours during which no short acting β2-agonist has been inhaled, and a
minimum of 48 hours for a long acting β2-agonist.
c. Patients who demonstrate an increase of ≥12% and ≥200 mL in FEV1 over their prebronchodilator value within 10-15 minutes after inhaling a total of 400 μg (4x100μg) of salbutamol/albuterol MDI (or equivalent dose of DPI) (the reversibility test). Reversibility will have to be demonstrated after an appropriate washout period of at least 6 hrs prior to the evaluation for a short-acting β2-agonist.
3. BMI must be within the range 18-32 kg/m2 (inclusive)
4. Vital signs (after 3 minutes resting measured in the supine position) not considered by the Investigator to be indicative of a disorder which would make it unsafe for subject to participate in the study or require medical intervention.
5. Able to communicate well with the investigator and comply with the requirements of the study. |
|
| E.4 | Principal exclusion criteria |
1. Women of child-bearing potential (WOCBP) - for explained definitions and exceptions see protocol.
2. Male subjects and their partners who are not using two highly effective methods.
3. Patients who have had previous intubation for a severe asthma attack/exacerbation.
4. Patients who have had a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to screening.
5. Patients who have had an emergency room visit for an asthma attack/exacerbation within 6 weeks prior to screening or any time between screening and Day -1 (Period 1).
6. Patients who have had a respiratory tract infection within 6 weeks prior to screening or any time between screening and pre-dose day 1.
7. Patients with seasonal allergy whose asthma is likely to deteriorate during the study period.
8. Patients with a known hypersensitivity to indacaterol or similar drugs.
9. Patients who require the use of ≥8 inhalations per day of the short-acting β2-agonist (100 μg/90 μg salbutamol/albuterol MDI or equivalent dose of DPI) on any 2 consecutive days from pre-screening.
10. Patients diagnosed with COPD as defined by the (GOLD Guidelines 2008).
11. Patients with concomitant pulmonary disease, pulmonary tuberculosis (unless confirmed by chest X-ray to be no longer active) or clinically significant bronchiectasis.
12. Any patient with lung cancer or a history of lung cancer.
13. Participation in any clinical investigation within 4 weeks prior to dosing or longer if
required by local regulation. Previous participation in a study with either the
investigational or comparator drugs does not exclude a patient from participation in this study.
14. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
15. Significant illness within the two weeks prior to dosing.
16. History of left-ventricular heart failure or symptomatic coronary atherosclerotic
cardiovascular disease (ie, angina, history of MI).
17. A past medical history of life-threatening arrhythmias or a history, or family history, of long QT syndrome.
18. Patients with a persistent systemic blood pressure ≥ 160/95 mmHg (whether treated or not), measured (in the dominant arm) on 2 separate occasions at least 24-hours apart.
19. Pregnant or nursing (lactating) women\
20. Patients with diabetes Type I or uncontrolled diabetes Type II including patients with a history of blood glucose levels consistently outside the normal range or HbA1c > 8.0% of total Hb measured at screening.
21. History of being immunocompromised, including a positive HIV (ELISA and Western blot) test result.
22. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
23. Patients who have ever received or are currently receiving treatment with omalizumab will not be allowed to participate in the study.
24. Treatments for asthma and allied conditions. For listed compounds see protocol.
25. Certain treatments should not be used unless they have been stabilized prior to
screening – for full list see protocol.
26. Other excluded medications – see full list in protocol
27. Use of any anti-tussive medication within 2 weeks prior to dosing. Use of opiates within 4 weeks prior to dosing.
28. Patients unable to successfully use a dry powder inhaler device or perform spirometry measurements.
29. A subject must not be randomized into this study more than once.
30. No person directly associated with the administration of the study may participate as a study subject. No family member of the investigational study staff may participate in this study.
31. No person who is considered vulnerable or person who is in detention may participate in this study.
32. In the UK only – Patients with hypokalemia, defined as Potassium below the lower limit of normal (dependent on the range applied by the laboratory assessing the sample).
33. In the UK only – Patients currently using medications as maintenance therapy for asthma which would need to be withdrawn/adjusted based on the requirements of the protocol as defined in Exclusion criterion 24. Effectively, in the UK, only patients using inhaled corticosteroids with short-acting β2 agonists are eligible for enrolment.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean change in FEV1 from baseline to post-dose trough following single dose treatment. Trough is defined as the mean of FEV1 at 23 hour 10 min and 23 hour 45mins post-dose. |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Inhaler device performance |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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
| |
| 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 | |
| E.8.9.1 | In the Member State concerned days | 77 |
| E.8.9.2 | In all countries concerned by the trial days | 77 |
Print
