A research study to find out whether a product to be tested (salmeterol xinafoate HFA pMDI 25 µg per actuation, manufactured by Cipla Ltd, India) is equivalent to the already existing formulation (salmeterol xinafoate HFA pMDI 25 µg per actuation (Serevent Evohaler™), supplied by Allen and Hanburys, UK) when administered by a volumatic spacer device to children with asthma
- Conditions
- AsthmaMedDRA version: 17.1Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2014-001946-10-BG
- Lead Sponsor
- Cipla Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
1. Informed consent by the subject’s parent /legal guardian/Assent (if possible also by the subject) given in a written form after being provided with detailed information about the nature, risks and scope of the clinical trial as well as the expected desirable and adverse effects of the drug.
2. Male or female (pre-menarchal and pre–pubescent) subjects aged 4 to 11 years.
3. Subjects not weighing less than 12 Kgs.
4. Body mass index (BMI) within the 5th to 125th percentile of the appropriate BMI designated charts based on stature-for-age and weight-for-age and by gender.
5. Subjects, who are stable on treatment with same dose of ICS and salbutamol sulphate as needed for the past 2 weeks prior to screening.
6. Subjects with physician diagnosed asthma as per the GINA guidelines.
7. Subjects aged 6 to 11 years with a FEV1 = 80% predicted at screening or subjects aged 4 to 5 years with a PEF >80% predicted or >85% of their personal best.
8. Subjects with no evidence of significant underlying disease other than asthma during the pre-study screening evaluation, medical history, laboratory tests, vital signs, and physical examination.
9. Subjects who agree to avoid strenuous physical exertion for at least 48 hours prior to dosing of each study period.
10. Subjects agree to abstain from consuming grapefruit or its products for at least 96 hours prior to dosing and until the last blood sample is withdrawn in a particular period
11. Subjects agree to abstain from consuming citrus fruits or their products and xanthine containing products (chocolate, tea, coffee or cola drink), for at least 2 hours prior to dosing and until the last blood sample is withdrawn in a particular period.
12. Subjects who agree to be available for the entire duration of the study and have the ability to understand and communicate effectively with the investigators and study personnel.
13. Subjects who are able to correctly use the pMDI with the volumatic spacer device, following training received from qualified site personnel.
Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. History of severe or life threatening asthma defined as any asthma episode associated with hypercapnea, intubation or admission to an intensive care unit.
2. Any use of salmeterol within 4 weeks prior to the Visit S.
3. Unstable asthma as evidenced by any change in asthma therapy within 2 weeks prior to screening or use of more than 4 puffs of rescue medication (salbutamol sulphate) per day within 1 week prior to screening.
4. Unstable asthma as evidenced by any change in asthma therapy within the last 3 months or admission to hospital due to asthma during or within the last 6 months before subject’s participation in the trial.
5. More than 1 short course of oral/systemic corticosteroids within 6 months preceding the Visit S, or any oral/systemic corticosteroids in the preceding 3 months.
6. Evidence of active concomitant pulmonary disease other than asthma (subjects with stable allergic rhinitis will be permitted as long as there are no changes in the treatment and the medications do not interfere with the analytical assay methods).
7. Subjects who have suffered any clinically significant illness in the two weeks prior to dosing or who have been hospitalised within 3 months preceding the start of the study.
8. Acute upper respiratory tract infection (URTI) that has not resolved within 4 weeks of the Visit S.
9. Acute lower respiratory tract infection (LRTI) that has not resolved within 8 weeks of the Visit S.
10. History of any clinically significant disease including but not limited to concomitant severe decompensated systemic disease (cardiovascular, renal, hepatic, endocrine, gastrointestinal, psychological, haematological, neurological, or immunological).
11. Clinically significant abnormal laboratory values.
12. Subjects who have a history of severe food allergy.
13. Known or suspected hypersensitivity to salmeterol xinafoate or any other constituents of the investigational products.
14. Use of any medication (prescription, non-prescription or herbal) other than salbutamol sulphate and the subject’s regular ICS within 4 weeks prior to the first dose of study medication unless complete elimination from the body can be assumed for the drug on the basis of the terminal elimination half-life (at least 5 times the elimination half-life to be elapsed) until the first dose of study medication.
15. Use of drugs which can specifically induce or inhibit enzyme Cytochrome P450 3A4 (CYP3A4) within 4 weeks prior to the first dose of the study medication.
16. Treatment with any investigational drug in the 3 months preceding the Visit S or 5 times the elimination half-life of that drug, whichever is longer.
17. Donation of blood in excess of 50 mL within 90 days prior to receiving the first dose of study medication.
18. Legal incapacity or other circumstances that render the subject’s parent or legal guardian unable to understand the nature, scope and possible consequences of the study.
19. In the investigator’s opinion, subjects unlikely to comply with the study procedures.
20. Subjects previously randomised into this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Pharmacokinetic Objective:<br>Phase I<br>To estimate intra-subject Coefficient of Variation (CV) in order to determine the sample size needed to establish bioequivalence between the test and reference product.<br>Phase II<br>To compare rate and extent of absorption of the test product, salmeterol xinafoate HFA pMDI 25 µg per actuation, with that of the reference product, SereventTM EvohalerTM (containing salmeterol xinafoate 25 µg per actuation), after single dose administration to paediatric asthma subjects with the aid of a volumatic spacer device.<br><br>;Secondary Objective: Safety Objective:<br>To compare the safety and tolerability of the test and reference product in paediatric asthma subjects.;Primary end point(s): Primary variables:<br>AUC(0-4hrs) and AUC(0-30min)<br><br>Secondary variables:<br>Cmax, tmax;Timepoint(s) of evaluation of this end point: At the end of trial
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The following safety variables will also be evaluated in the study:<br>- Adverse events<br>- Vital signs<br>- Overall well-being<br>- Laboratory assessments (haematology, biochemistry and urinalysis);Timepoint(s) of evaluation of this end point: On an ongoing basis