E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Persistent Asthma in Adults and Adolescents. |
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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 |
The primary objective is to compare the efficacy of FF/GW642444 100/25 mcg, administered once daily in the evening with FP/salmeterol 250/50 mcg administered twice daily in subjects 12 years of age and older with persistent bronchial asthma over a 24 week treatment period. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent: Subjects must give their signed and dated written informed consent to participate 2. Type of Subject: Outsubjects 12 years of age or older at Visit 1 (or ≥18 years of age if local regulations or the regulatory status of study medication permit enrolment of adults only) with a diagnosis of asthma as defined by the National Institutes of Health [NIH, 2007] at least 12 weeks prior to Visit 1. 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, etonogestrel • Injectable progestogen • Oral contraceptive (either combined oestrogen/progestin or progestin only) • Any intrauterine device (IUD) with a documented failure rate of less than 1% per year • Double barrier method–spermacide plus a mechanical barrier (e.g., spermacide plus a male condom or a spermacide and female diaphragm). • Oestrogenic vaginal ring • Percutaneous contraceptive patches • Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical study and for a period after the study 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 is required for females of childbearing potential at the initial screening visit (Visit 1) and Visit 6 or early withdrawal. In addition, a urine pregnancy test will be performed on all females of childbearing potential at Visit 2 (Randomisation). Subjects will be given a home urine pregnancy kit for use during the follow-up period. 4. Severity of Disease: A best evening pre-bronchodilator FEV1 of ≥40%- and ≤85% of the predicted normal value. Predicted values will be based upon NHANES III [Hankinson, 1999]. 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 is recorded as being of African-American/African heritage race, then the African-American equations will be used. If a subject is recorded as being of Asian race, then the Asian adjustment will be used [Hankinson, 2010]. Otherwise, the Caucasian equations will be used. 5. Reversibility of Disease: Demonstrated a ≥12% and ≥200ml reversibility of FEV1 within 10-40-minutes following 2-4 inhalations of salbutamol/albuterol inhalation aerosol or equivalent dose of nebulised salbutamol/albuterol at the Screening Visit. 6. Current Anti-Asthma Therapy: Subjects must have been using an inhaled corticosteroid for at least 12 weeks prior to Visit 1 and be maintained on a medium dose (e.g. FP 250 mcg twice daily) for at least 4 weeks prior to Visit 1view protocol for further information. 7. Short-Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with salbutamol/albuterol inhaler at Visit 1 for use as needed for the duration of the study. Subjects must be able to withhold salbutamol/albuterol for at least 6 hours prior to lung function assessments. |
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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 hypercapnoea, respiratory arrest or hypoxic seizures within the last 5 years. 2. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks prior to Visit 1 and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject’s asthma status or the subject’s ability to participate in the study. 3. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids or that resulted in overnight hospitalisation requiring additional treatment for asthma within 12 weeks prior to Visit 1. 4. 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. 5. Other Concurrent Diseases/Abnormalities: A subjects must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study view page 18 of the protocol for futher information. 6. Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of candidiasis at Visit 1. 7. Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½) of the prior investigational study (whichever is longer of the two). 8. Allergies: • Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the novel dry powder inhaler or ACCUHALER™/DISKUS™ (i.e., lactose or magnesium stearate). • Milk Protein Allergy: History of severe milk protein allergy. 9. Concomitant Medication: • Administration of prescription or over the counter medication that would significantly affect the course of asthma, or interact with study drug, such as: anticonvulsants (barbiturates, hydantoins, carbamazepine); polycyclic antidepressants; beta-adrenergic blocking agents; phenothiazines and monoamine oxidase (MAO) inhibitors. • Immunosuppressive Medications: A subject must not be using or require use of immunosuppressive medications during the study. • Note: Immunotherapy for the treatment of allergies is allowed during the study provided it was initiated 4 weeks prior to Visit 1 and subjects remain in the maintenance phase for the duration of the study. • Cytochrome P450 3A4 (CYP3A4) inhibitors: Subjects who have received a potent CYP3A4 inhibitor within 4 weeks of Visit 1(e.g., ritonavir, ketoconazole, itraconzole). 10. Compliance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol, including visit schedule. 11. Tobacco Use: Current smoker or with a smoking history of 10 pack years (e.g., 20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars or pipe tobacco). 12. 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. 13. Night shift workers: No subject is permitted to perform night shift work for 1 week prior to Visit 1 until completion of the study treatment period.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Weighted mean for 24 hour serial FEV1 will be calculated from serial spirometry over 0 to 24 hours, at the end of 168-day double-blind treatment period. The 24-hour serial FEV1 will include post-dose assessments after 5, 15, 30 minutes and 1, 2, 3, 4, 11, 12, 12.5, 13, 14, 16, 20, 23 and 24 hours. IMPORTANT: To ensure that the pre-dose FEV1 assessment at the start of the final 24 hour (over which where FEV1 will measured serially) is a genuine trough measure, subjects should be instructed to take their medications at 24 hours and 12 hours prior to the planned timing of the end of treatment visit (Visit 6). Investigators (or site staff) should plan a phone contact (Phone contact 2) to remind subjects of the timing of dosing. The final dose will be given under supervision at the clinic During the serial FEV1 (0-24hours) procedure, the morning dose of double-blind medication will be taken within 5 minutes following 12 hour FEV1 assessment. |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
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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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End of trial will be defined by Last Subject Last Visit. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |