Asthma
Conditions
Keywords
asthma, fluticasone propionate/salmeterol, PK equivalence, COPD, pharmacokinetics, fluticasone propionate/salmeterol in a capsule-based inhaler, fluticasone propionate/salmeterol in a multi-dose dry powder inhaler, Respiratory
Brief summary
This study will compare the pharmacokinetic (PK) of Fluticasone Propionate/Salmeterol combination (FSC) 100/50 micrograms (mcg) delivered via the capsule-based inhaler (Rdpi) relative to FSC 100/50 mcg delivered via the multi-dose dry powder inhaler (Ddpi) to establish whether the Rdpi inhaler has exposure (in terms of fluticasone propionate area under time concentration curve \[AUC\] and Salmeterol maximum concentration \[Cmax\]) no greater than 1.2500 compared to the Ddpi, sufficient to allow progression to Phase 3. This study will enroll 36 healthy adult male and female subjects and each subject will be allocated to one of two sequences and will participate in four treatment periods, receiving each of the treatments twice.
Interventions
DRUGFluticasone Propionate / Salmeterol Xinafoate DISKUS
Fluticasone propionate and salmeterol xinafoate combination as a dry powder inhaler for oral inhalation with unit dose strength of 100/50 mcg (available in blister pack) administered via DISKUS (Ddpi) device.
DRUGFluticasone Propionate / Salmeterol Xinafoate ROTACAP
Fluticasone propionate and salmeterol xinafoate combination as a dry powder inhaler for oral inhalation with unit dose strength of 100/50 mcg (available in blister pack) administered via ROTAHALER (Rdpi) device.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the Investigator determines that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body mass index within the range 18 to 35 kilograms/meter squared (m\^2) (inclusive). * A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy (for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records); or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \> 40 milli international unit/mililiter \[mL\] and estradiol \< 40 picogram/mL \[\<147 picomoles/liter\] is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotropin (hCG) test at screening or prior to dosing. Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 2 days post-last dose. OR has only same-sex partners, when this is her preferred and usual lifestyle. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Alanine aminotransferase, alkaline phosphatase and bilirubin \<= 1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 %). * Based on single or averaged QT interval corrected (QTc) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's formula (QTcF)\<450 millisecond (msec), and QT duration corrected for heart rate by Bazett's formula (QTcB)\<480 msec in subjects with Bundle Branch Block.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of PK parameters of FSC delivered via the Rdpi relative to FSC delivered via the Ddpi | PK samples will be collected at pre-dose, 5 minutes (mins), 10 mins, 30 mins, 1, 2, 4, 8, 10, and 12 hours post dose on Day 4 of each treatment period. | PK Parameters include: area under the plasma fluticasone propionate concentration-time curve over dosing interval (AUCtau), salmeterol maximum plasma concentration-time curve on the last day of each study treatment period (Cmax). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of PK parameters of FSC delivered via the Rdpi relative to FSC delivered via the Ddpi | PK samples will be collected at pre-dose, 5 minutes (mins), 10 mins, 30 mins, 1, 2, 4, 8, 10, and 12 hours post dose on Day 4 of each treatment period. | PK Parameters include: area under the plasma salmeterol concentration-time curve over dosing interval (AUCtau), fluticasone propionate maximum plasma concentration-time curve on the last day of each study treatment period (Cmax), and fluticasone propionate and salmeterol time of occurence of Cmax (Tmax) on the last day of each treatment period (Day 4). |
| Number of participants with adverse events (AEs) as measure of safety and tolerability. | 35 days. | AEs will be collected from the start of study treatment and until the follow-up contact. |
| Laboratory parameters as a measure of safety and tolerability. | 35 days | Laboratory parameters include: hematology, clinical chemistry, urinalysis and additional parameters. |
| Vital sign measurement as measure of safety and tolerability. | 35 days. | Vital parameters include: systolic blood pressure, diastolic blood pressure, and pulse rate. |
Countries
Australia
Outcome results
None listed