| 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 | 9.1 |
| 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 |
| To evaluate the bronchodilatory efficacy, in terms of trough FEV1, of indacaterol (500 μg) in combination with mometasone furoate (400 μg) delivered as 2 inhalations of QMF149 (indacaterol 250 μg/mometasone furoate 200 μg) via the Twisthaler ® versus matched QMF149 placebo in patients with persistent asthma. (Trough FEV1 is defined as the mean of 2 measurements at 23 h10 min and 23 h 45 min post-dose). |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the bronchodilatory efficacy, in terms of peak FEV1, of indacaterol (500 μg) in combination with mometasone furoate (400 μg) delivered as 2 inhalations of QMF149 (indacaterol 250 μg/mometasone furoate 200 μg) via the Twisthaler® versus matched QMF149 placebo in patients with persistent asthma. (Peak FEV1 is defined as the peak FEV1 between 0 and 4h post dose)
- To evaluate the bronchodilator effects of indacaterol (500μg) in combination with mometasone furoate (400 μg) delivered as 2 inhalations of QMF149 (indacaterol 250 μg/mometasone furoate 200 μg) via the Twisthaler® versus matched QMF149 placebo as measured by FEV1, FVC and FEV1/FVc ratio at each time point post dose
- To evaluate the effects of treatment between Seretide® Accuhaler® (50/250 b.i.d.) vs. placebo for all the efficacy variables above
- To assess the pharmacokinetics of indacaterol and mometasone furoate following single dose administration as a fixed combination (QMF149) via the Twisthaler®. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male and 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 Visit 1.
2. Patients with persistent asthma, diagnosed according to the GINA Guidelines, 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 Visit 1.
b. Patients with an FEV1 at Visit 1 of ≥50% of the predicted normal value. 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 30 minutes after inhaling a total of 200 μg of salbutamol (or 180 μg albuterol) via MDI (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. The administration of salbutamol(or albuterol) for the reversibility test is to be within 30 minutes after pre-bronchodilator spirometry. Reversibility has to be demonstrated at Visit 1 or between Visits 1 and 2, in order for patients to be included in the trial.
d. For each patient, the smaller value of the Visit 1 FEV1 or the Visit 2 FEV1 pre- dose value must be at least 85% of the larger value.
3. At Screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed after the subject has rested for at least three (3) minutes, and again when required after three minutes in the standing position. Vital signs should be within the following ranges:
oral body temperature between 35.0-37.5 °C
systolic blood pressure, 90-160 mm Hg
diastolic blood pressure, 50-95 mm Hg
pulse rate, 50 - 90 bpm
When blood pressure and pulse will be taken again after 3 minutes standing, there shall be no more than a 30 mm Hg drop in systolic or 20 mm Hg drop in diastolic blood pressure associated with clinical manifestation of postural hypotension.
4. Body mass index (BMI) must be within the range of 18 to 32. Subjects must weigh at least 50 kg to participate in this study.
5. Female subjects of child bearing potential must be using a local contraception in the three months following last study drug administration; double methods are preferred, i.e. intrauterine device plus condom, or spermicidal gel plus condom, but single methods, i.e. oral, mechanical, subcutaneous or surgical contraception, are acceptable
6. Male subjects must be using a local contraception for the entire duration of the study, up to Study Completion visit, and refrain from fathering a child in the three (3) months following last study drug administration. Double methods are preferred, i.e., intra-uterine device plus condom, or spermicidal gel plus condom, but single methods, i.e., oral, mechanical, subcutaneous or surgical contraception, are acceptable.
7. Able to communicate well with the investigator, to understand and comply with the
requirements of the study. Understand and sign the written informed consent.
8. Subjects screened in France must be registered in the French Health Ministry’s computerized national volunteer file and authorized to participate in a clinical trial.
9. Subjects screened in France must be covered by a French Health Insurance plan or benefit from such a plan as a third party in accordance with the French law on biomedical research |
|
| E.4 | Principal exclusion criteria |
1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female patient after conception and until the termination of gestation, confirmed by a positive serum hCG laboratory test (> 5 IU/ml) (Postmenopausal female subjects with no regular menstrual bleeding for more than 1 year do not need pregnancy testing, but their menopause must be confirmed by a plasma FSH level of >40 IU/L.)
2. Patients who have used tobacco products within the 6 month period prior to Visit 1, or who have a smoking history of greater than 10 pack years
3. Patients diagnosed with COPD as defined by the GOLD guidelines
4. Patients who have had a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to Visit 1.
5. Patients requiring more than 8 puffs of rescue medication per 24 hours on 2 consecutive days during the run-in period.
6. Patients who have had an acute asthma attack/ exacerbation requiring an ER visit or a respiratory tract infection within 6-weeks prior to Visit 1 or at any time between Visit 1 and Visit 2.
7. Patients who, in the judgment of the investigator or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as unstable ischemic heart disease, arrhythmia , uncontrolled hypertension, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state, ophthalmologic disorder, that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study.
8. Any patient with active cancer or a history of cancer with less than 5 years disease free survival time. Localized basal cell carcinoma of the skin is acceptable. Patients with a history of cancer and 5 years or more disease free survival time may be included in the study by agreement with Novartis H.Q. personnel on a case-by-case basis.
9. Patients with a history of long QT syndrome or whose QTc interval measured at Visit 1 or Visit 2 is prolonged: > 430 ms (males) or > 440 ms (females) as assessed by the investigator’s interpretation. Patients who fail the screening ECG should not be re-screened.
10. Patients with a history of hypersensitivity to any of the study drugs or to drugs with similar chemical structures including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
11. Patients who have had live attenuated vaccinations within 30 days prior to Visit 1 or during the screening/run-in period.
12. Patients with a known history of non-compliance to medication.
13. Treatments for asthma and allied conditions: the following medications must not be used prior to Visit 1 for at least the minimum washout period specified below or at any time during the study(Long acting anti-cholinergic agent tiotropium, Short acting anti-cholinergics, Fixed combinations of β2-agonists and inhaled corticosteroids, Theophylline and other xanthines, Parenteral or oral corticosteroids, Leukotriene antagonists, ketotifen, inhaled cromolyn, nedocromil)
14. The following medications must not be used prior to Visit 1 for at least the minimum washout period specified below (Long-acting β2-agonists, Short acting β2-agonists )
15. Treatments for asthma: The following medications should not be used unless they have been stabilized prior to Visit 1:Antihistamines, Inhaled nasal cromolyn and inhaled nasal corticosteroids, Omalizumab, Maintenance Immunotherapy.
16. Other excluded medications:Non-potassium sparing diuretics, β-blocking agents, Drug with potential to significantly prolong the QT interval, Tricyclic antidepressants and monoamino-oxidase inhibitors, Any known medications that induce or inhibit CYP3A4 .
17. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives prior to Visit 1, whichever is longer.
18. Patients unable to use a dry powder inhaler device or perform spirometry measurements
19. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
20. History of immunodeficiency diseases, including a positive HIV test result.
21. History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.
22. Donation or loss of 400 ml or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation (3months for France).
23. In custody due to an administrative or a legal decision, or under tutelage, or being admitted to a sanitary or social institution.
24. Inability to be contacted in case of emergency.
25. Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, or other staff directly involved in the conduct of the protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) | |
| 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 | No |
| 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 | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 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 | 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 | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
Print
