E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
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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 establish a model of dose-dependent bronchodilation that will be used to establish the pharmacodynamic equivalency of the LABA component of new combination asthma drug treatments. The intention to better characterize the timecourse of bronchodilatory changes following a single treatment with 3 doses of Advair® 100 / 50 (1 puff, 2 puffs or 4 puffs; equivalent to 100/50, 200/100 and 400/200 mcg, fluticasone/salmeterol respectively). |
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E.2.2 | Secondary objectives of the trial |
To investigate the effects of Advair® 100 / 50 (1 puff, 2 puffs or 4 puffs) on blood potassium and heart rate as potential pharmacodynamic markers. Also to measure the pharmacokinetics of salmeterol administered as a combination dry powder in this study to allow for PK/PD interrelationship. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult males and females ≥ 18 years with BMI 19 to 32 kg/m2 (inclusive) and a bodyweight ≥ 50 kg. 2. Patients with a clinical diagnosis of mild to moderate asthma (defined as satisfying the Global Initiative in Asthma [GINA] definition of asthma or has satisfied in the past and have a pre-bronchodilator forced expiratory volume in 1 second (FEV1) >50% at Screening. 3. Patients must demonstrate ≥ 15% reversibility (and a ≥ 200 mL difference) from prebronchodilator FEV1 within 15 to 30 minutes of receiving up to 400 mcg salbutamol by MDI with spacer or up to 5 mg salbutamol by nebulizer at Screening. 4. Patients who if female, are not currently pregnant or breast feeding and are using medically acceptable methods of contraception. 5. Patients whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator. 6. Patients who are negative for HBsAg, hepatitis C antibody and HIV I and II test at screening. 7. Patients who are negative for drugs of abuse and alcohol tests at screening and admission. 8. Patients who are non-smokers for at least 3 months prior to screening. 9. Patients who have a < 10 pack-year smoking history. 10. Patients who are able and willing to give written informed consent. 11. Patients who are able to use an inhaled medical device, as demonstrated by the use of a flow loop assessment. 12. Medical history must be verified by either a personal physician or medical practitioner as appropriate. |
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E.4 | Principal exclusion criteria |
1. Patients who do not conform to the above inclusion criteria. 2. Patients who have a clinically relevant history or presence gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders which would preclude participation in the opinion of the Investigator. 3. Patients who have a clinically relevant medical or surgical history that would preclude the administration of inhaled corticosteroids as indicated in the patient information leaflet for Seretide Accuhaler or Advair® Diskus®. 4. Patients who have a QTc of > 500 msec. 5. Patients who have a history of relevant drug hypersensitivity. 6. Patients who have a history of alcoholism. 7. Patients who have a history of drug abuse. 8. Patients receiving oral or parenteral corticosteroid treatment within 4 weeks of Randomization for exacerbation of their asthma or who have been intubated for ventilation in the past 5 years or are considered to have very severe asthma. 9. Patients who are currently taking inhibitors of CYP3A4 such as ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, or telethromycin. 10. Patients who consume more than 28 units (male)/ 21 units (female) of alcohol a week.unit = 1 (125 mL) glass of wine = 1 measure of spirits = ½ pint of beer 11. Patients who have a significant infection or known inflammatory process on screening. 12. Patients who have acute gastrointestinal symptoms at the time of screening and/or admission (e.g. nausea, vomiting, diarrhoea, heartburn). 13. Patients who have an acute respiratory infection such as influenza at the time of screening and/or admission. 14. Female patients who are pregnant, trying to become pregnant, breast feeding, or not using an acceptable method of contraception. 15. Patients who have used any investigational drug in any clinical trial within 3 months of receiving the last dose. 16. Patients who have received the last dose of IMP greater than 3 months ago but who are on extended follow-up requiring blood sampling. 17. Patients using medication, which in the opinion of the Investigator will affect the outcome of the study. 18. Patients who have donated and/or received any blood or blood products within the previous 3 months prior to first dosing (to review on a case by case basis). 19. Patients who cannot communicate reliably with the investigator. 20. Patients who are unlikely to co-operate with the requirements of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To establish a model of dose-dependent bronchodilation that will be used to establish the pharmcodynamic equivalency of the LABA component of new combination of asthma drugs and to investigate the pharmacokinetics of salmeterol administered as a combination dry powder in this study to allow for investigation of PK/PD interrelationship treatments. |
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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 | No |
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) | Yes |
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 | No |
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) | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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
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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 | |