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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01494610




Registration number
NCT01494610
Ethics application status
Date submitted
27/10/2011
Date registered
19/12/2011
Date last updated
26/02/2019

Titles & IDs
Public title
Pharmacokinetic and Pharmacodynamic (PK and PD) Study of Fluticasone Propionate and Salmeterol Combination Product Delivered in a Capsule-based Inhaler and in a Multi-dose Dry Powder Inhaler in Moderate Asthma Patients and Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Patients.
Scientific title
A Comparative Bioavailability Study to Compare the Pharmacokinetic (PK) and Pharmacodynamic (PD) Effects of Fluticasone Propionate and Salmeterol Delivered by Fluticasone Propionate/ Salmeterol Combination in a Capsule-based Inhaler and a Multi-dose Dry Powder Inhaler, in Moderate Asthma Patients and Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Patients.
Secondary ID [1] 0 0
114334
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SERETIDE Rotacaps
Treatment: Drugs - SERETIDE Diskus

Experimental: SERETIDE Rotacaps - Fluticasone propionate (250 micrograms [ug])/Salmeterol (50 ug) combination delivered in a capsule-based inhaler

Active Comparator: SERETIDE Diskus - Fluticasone propionate (250 ug)/Salmeterol (50 ug) combination delivered in a multi-dose dry powder inhaler

Placebo Comparator: Placebo Rotacaps - Placebo delivered in a capsule-based inhaler

Placebo Comparator: Placebo Diskus - Placebo delivered in a multi-dose dry powder inhaler


Treatment: Drugs: SERETIDE Rotacaps
The study consists of four treatment periods of 10 +/- 1 days each in a cross-over fashion. Each patient will be administered SERETIDE delivered via a capsule-based inhaler (Rotacaps) twice for two treatment periods and a placebo delivered via a capsule-based inhaler (Rotacaps) twice for two treatment periods in a randomised, double-blind, double-dummy fashion. Dosing is twice daily in the morning and evening over the duration of each treatment period.

Treatment: Drugs: SERETIDE Diskus
The study consists of four treatment periods of 10 +/- 1 days each in a cross-over fashion. Each patient will be administered SERETIDE delivered via a multi-dose dry powder inhaler (Diskus) twice for two treatment periods and a placebo delivered via a multi-dose dry powder inhaler (Diskus) twice for two treatment periods in a randomised, double-blind, double-dummy fashion. Dosing is twice daily in the morning and evening over the duration of each treatment period.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Area Under the Concentration Time Curve Over the Dosing Period (AUC[0-tau]) for FP
Timepoint [1] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Primary outcome [2] 0 0
Weighted Mean Serum Cortisol (SC) Over 0 to 12 Hours Post Dose
Timepoint [2] 0 0
At pre-morning dose; 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [1] 0 0
Mean Plasma AUC(0-tau) and Plasma AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-tlast]) for Salmeterol
Timepoint [1] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [2] 0 0
Mean AUC(0-tlast) for FP
Timepoint [2] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [3] 0 0
Mean Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of FP
Timepoint [3] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [4] 0 0
Mean Terminal Phase Half-life (t1/2) for FP
Timepoint [4] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [5] 0 0
Time of Occurrence of Cmax (Tmax) for FP
Timepoint [5] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [6] 0 0
Mean Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) for Salmeterol
Timepoint [6] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [7] 0 0
Mean Terminal Phase Half-life (t1/2) for Salmeterol
Timepoint [7] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [8] 0 0
Tmax for Salmeterol
Timepoint [8] 0 0
At pre-morning dose; 5, 10, 30 minutes post-dose (PD); and 1, 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [9] 0 0
Mean Urine Cortisol Excretion Over 0 to 24 Hours Post Dose for FP
Timepoint [9] 0 0
0-24 hours post dose on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [10] 0 0
Serum Cortisol Minimum (Cmin) for FP
Timepoint [10] 0 0
Day 10 of each study period (Periods 1-4); Study Day 10 (+/-1) (reference day is Study Day 1 or Randomization day), Period 1; Study Day 20 (+/-1), Period 2; Study Day 30 (+/-1), Period 3; Study Day 40 (+/-1), Period 4
Secondary outcome [11] 0 0
Weighted Mean Over 0 to 4 Hours Post Dose of Heart Rate for Salmeterol
Timepoint [11] 0 0
At pre-morning dose; 15, 30, 60, 90 minutes post-dose (PD); and 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [12] 0 0
Mean of Maximum Heart Rate Over 0 to 4 Hours Post Dose for Salmeterol
Timepoint [12] 0 0
At pre-morning dose; 15, 30, 60, 90 minutes post-dose (PD); and 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [13] 0 0
Minimum Diastolic Blood Pressure (DBP), Maximum Systolic Blood Pressure (SBP), and Weighted Mean for DBP and SBP Over 0 to 4 Hours Post Dose
Timepoint [13] 0 0
At pre-morning dose; 15, 30, 60, 90 minutes post-dose (PD); and 2, 4, 8, 10, and 12 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [14] 0 0
Maximum and Weighted Mean Over 0 to 4 Hours Post Dose of the QT Interval Corrected According to Bazett's Formula (QTc[B]) and the QT Interval Corrected According to Fridericia's Formula (QTc[F])
Timepoint [14] 0 0
At pre-morning dose; 15, 30, 60, 90 minutes post-dose (PD); and 2, 3 and 4 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [15] 0 0
Weighted Mean Over 0 to 4 Hours Post Dose of Plasma Potassium and Minimum (Min) Plasma Potassium
Timepoint [15] 0 0
At pre-morning dose; 30, 60 minutes post-dose (PD); and 2 and 4 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [16] 0 0
Weighted Mean Over 0 to 4 Hours Post Dose and Maximum Plasma Glucose
Timepoint [16] 0 0
At pre-morning dose; 30, 60 minutes post-dose (PD); and 2 and 4 hours PD on Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [17] 0 0
Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cell (WBC) Count
Timepoint [17] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [18] 0 0
Mean Hemoglobin and Mean Corpuscular Hemoglobin (MCH) Concentration
Timepoint [18] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [19] 0 0
Red Blood Cell (RBC) Count and Reticulocytes
Timepoint [19] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [20] 0 0
Mean Corpuscule Hemoglobin (MCH)
Timepoint [20] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [21] 0 0
Mean Corpuscle Volume (MCV)
Timepoint [21] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [22] 0 0
Mean Hematocrit
Timepoint [22] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [23] 0 0
Mean Albumin and Total Protein
Timepoint [23] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [24] 0 0
Mean Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amio Transferase (AST), and Gama Glutamyl Transferase (GGT)
Timepoint [24] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [25] 0 0
Mean Direct Bilirubin (DB), Total Bilirubin (TB), Creatinine, and Uric Acid
Timepoint [25] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [26] 0 0
Mean Calcium, Chloride, Glucose, Potassium, Sodium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicar), and Urea/Blood Urea Nitrogen (BUN)
Timepoint [26] 0 0
Day 10 of each study period (P): Study Day (SD) 10 (reference day is SD 1 or Randomization day), 20, 30, and 40 (+/-1) for P 1, 2, 3, and 4, respectively
Secondary outcome [27] 0 0
Number of Participants With an Adverse Event (AE)
Timepoint [27] 0 0
Randomization (Day 1) up to Follow-up (Days 47-50)

Eligibility
Key inclusion criteria
INCLUSION CRITERIA:

ALL PATIENTS:

- Available for the duration of the study and able to attend the clinic for all study
visits.

- Gender: male or female

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; or postmenopausal defined as 12 months of spontaneous
amenorrhea [in questionable cases a blood sample with simultaneous follicle
stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is
confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal
status is in doubt will be required to use one of the protocol allowed 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 2-4 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 and agrees to use one of the protocol allowed 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 they
have attended the site for the follow-up visit.

- Capable of giving informed consent, which includes compliance with the study
requirements and restrictions listed in the consent form.

- Body mass index between 18 and 35 kg/m2 inclusive at Screening

- Able to use the inhaler devices adequately after training

- AST and ALT < 2xULN (upper limit of normal); alkaline phosphatase and bilirubin less
than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%).

- QT interval corrected for heart rate (QTc)* <450 millisecond (msec)** QTc <480 msec
for patients with bundle branch block

- either QTcB (QTc Bazzett's formula) or QTcF (QTc Fridericia's formula), machine
or manual overread, males or females. The specific formula that will be used in a
study should be predetermined prior to the initiation of the study. The QT
correction formula used to determine inclusion and discontinuation should be the
same throughout the study.

- based on single or averaged QTc values of triplicate ECGs obtained over a
brief recording period

COPD PATIENTS:

- Diagnosis: COPD patients, defined as either Stage III to Stage IV COPD diagnosis
according to GOLD criteria (Global Strategy for the Diagnosis, Management, and
Prevention of COPD, updated 2009) [GOLD, 2009]. Individuals must be otherwise healthy
individuals who are free from significant cardiac, gastrointestinal, hepatic, renal,
haematological malignancy, endocrine, neurological and psychiatric disease as
determined by history, physical examination and screening investigations.

- Age: 40-80 years inclusive at the time of signing the informed consent.

- Post-bronchodilator forced expiratory volume in one second (FEV1) < 50% of predicted
normal values at Screening. Patients must abstain from short acting beta agonist
(SABA) use for 6 hours prior to the screening visit.

- Post-bronchodilator FEV1/FVC ratio = 0.70 at Screening

- An increase of less than 15% from baseline FEV1 or an absolute change of < 200ml, 30
minutes after inhalation of 400mcg of salbutamol by metered-dose inhaler (MDI) and
spacer or 2.5mg by nebuliser at Screening.

- Ex smokers for at least the past 3 months with a pack history =10 pack years [number
of pack years = (number of cigarettes per day / 20) x number of years smoked].

- COPD therapy:

- Patients on fluticasone propionate/salmeterol combination 250/50mcg bid via a
multi-dose dry powder inhaler prior to the study will be allowed to remain on their
treatment regimen until randomization provided all other eligibility criteria are met.

- Patients on fluticasone propionate/salmeterol combination 250/50mcg bid via a metered
dose inhaler or the equivalent dose of budesonide/formoterol, 800/24mcg (total daily
dose) via a turbuhaler will be switched to fluticasone propionate/salmeterol
combination 250/50mcg bid via the GSK provided multi-dose dry powder inhaler for
between 14 and 28 days prior to randomization.

- Patients on tiotropium in addition to ICS/LABA (long-acting beta agonist) treatment
(up to a total daily dose of 500mcg fluticasone propionate or other ICS equivalent eg.
800mcg budesonide) may continue their tiotropium treatment throughout the study.

- Patients on tiotropium monotherapy will need to start treatment with fluticasone
propionate/salmeterol combination 250/50mcg bid via the GSK provided multi-dose dry
powder inhaler for between 14 and 28 days prior to randomization. They may continue
their tiotropium treatment throughout the study.

- Patients on LABA therapy (eg. salmeterol 50mcg) will need to start treatment with
fluticasone propionate/salmeterol combination 250/50mcg bid via the GSK provided
multi-dose dry powder inhaler for between 14 and 28 days prior to randomization.

ASTHMA PATIENTS:

- Diagnosis: Patients with moderate asthma as defined by the Global Initiative for
Asthma (GINA) guidelines at Screening. A best FEV1 of 60-85% of the predicted normal
value at the Screening visit. NHANES (National Health and Nutrition Examination
Survey) III predicted values will be used [Hankinson, 2009]. 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 or of Pacific Islander race, then the Caucasian
formula will be used with a conversion factor of 0.88. Otherwise, the Caucasian
equations will be used.

- Age: 18 and above at the time of signing the informed consent.

- Best clinic screening pre-bronchodilator FEV1 between 60 and 85% of predicted normal
values (NHANES III values). Patients must abstain from SABA use for 6 hours prior to
the Screening visit.

- Asthma therapy:

- Patients on fluticasone propionate/salmeterol combination 250/50mcg treatment via a
multi-dose dry powder inhaler prior to the study will be allowed to remain on their
treatment regimen until randomization provided all other eligibility criteria are met.

- Patients on treatment with ICS alone (up to a total daily dose of 500mcg fluticasone
propionate or other ICS equivalent eg. 800mcg budesonide) will be required to switch
treatment to fluticasone propionate/salmeterol combination 250/50mcg bid via the GSK
provided multi-dose powder inhaler for between 14 and 28 days prior to randomization
if deemed appropriate.

- Patients on treatment with budesonide/eformoterol combination (up to a total daily
dose of 800/24mcg via a Turbuhaler) will be required to switch to fluticasone
propionate/salmeterol combination 250/50mcg bid via the GSK-provided multi-dose powder
inhaler for between 14 and 28 days prior to randomization.

- Patients on treatment with fluticasone propionate/salmeterol combination at a dose up
to 250/50mcg bid via a metered dose inhaler or multi-dose dry powder inhaler (eg.
100/50mcg) will be required to switch to fluticasone propionate/salmeterol combination
250/50mcg bid via the GSK-provided multi-dose powder inhaler for between 14 and 28
days prior to randomization.

EXCLUSION CRITERIA:

ALL PATIENTS:

- Any clinically relevant medical condition or abnormality identified during the
screening medical assessment and procedures, physical examination, or laboratory
assessments (including clinical chemistry and haematology), which in the opinion of
the GSK Medical Monitor is likely to affect the safety of the subject and/or interfere
with the study procedures and outcomes.

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody or
positive HIV test result within 3 months of screening.

- Patients on treatment with fluticasone propionate either as monotherapy or in
combination at a total daily dose higher than 500mcg or budesonide monotherapy or in
combination at a total daily dose higher than 800mcg are excluded from the study

- Use of oral/injectable/depot corticosteroid for any indication within 3 months prior
to the Screening visit.

- Use of intra-nasal steroids (INS). To be eligible for the study, patients on INS
therapy will be required to switch to non-INS therapy at randomization.

- Patients with abnormal levels of serum cortisol at Screening

- Abuse of alcohol consumption within 12 months of the Screening visit defined by the
following Australian guidelines:

Males: An average weekly intake greater than 21 units or an average daily intake greater
than 3 units. Females: An average weekly intake greater than 14 units or an average daily
intake greater than 2 units.

One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of
spirits and 100 mL of wine.

- A known or suspected history of drug abuse within 12 months of the Screening visit.

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Where participation in the study would result in donation of blood or blood products
in excess of 500mL within a 56-day period.

- Known hypersensitivity to salbutamol or any ingredient in the study medication
preparation and/or history of any other drug or other allergy that, in the opinion of
the GSK medical monitor and the investigator contraindicates participation of the
subject

- Grapefruit or grapefruit juice containing products are excluded from 2 weeks prior to
randomisation until collection of the final blood sample at treatment period 4.

- Drugs that inhibit the cytochrome P450 isoform, 3A4 (CYP3A4), are excluded from 2
weeks prior to randomisation until collection of the final blood sample at treatment
period 4. CYP3A4 inhibitors include cimetidine, clarithromycin, erythromycin,
ciprofloxacin, ritonavir, ketoconazole, and azole antifungals, a complete list is
provided in the protocol.

- Use of prescription or non-prescription drugs, vitamins, herbal and dietary
supplements, within seven days or 5 half-lives (whichever is longer) prior to the
first dose of study medication, which in the opinion of the Principal Investigator,
may interfere with study outcome. Specifically, calcium and vitamin D supplements and
bisphosphonates are not allowed throughout the study.

- Pregnant females as determined by positive serum or urine ßhCG (ß-human chorionic
gonadotropin) test at Screening or prior to dosing.

- Patients, who, in the opinion of the Investigator, are not able to comply with the
protocol requirements.

COPD PATIENTS:

- Subjects with a respiratory disorder in addition to COPD (e.g. bronchiectasis,
fibrosis) or significant co-morbidity that might affect lung function (e.g. poorly
controlled heart failure, atrial fibrillation or ischaemic heart disease).

- Regular oxygen or nebulised bronchodilator therapy

- The subject has history of a respiratory infection (including sinusitis) within 4
weeks prior to the Screening visit

- Any previous lung resection surgery (eg., lung volume reduction surgery or lobectomy)

ASTHMA PATIENTS:

- Acute exacerbation of asthma requiring hospitalisation in the 6 weeks prior to the
Screening visit.

- Subjects may not have used inhaled tobacco products within the past 3 months (ie.
cigarettes, cigars or pipe tobacco) or have historical use of 10 pack years or more;
[number of pack years = (number of cigarettes per day / 20) x number of years smoked].
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/06/2011
Sample size
Target
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a comparative bioavailability study to compare the pharmacokinetics and
pharmacodynamic effects of Fluticasone propionate and Salmeterol delivered in a capsule-based
inhaler versus a multi-dose dry powder inhaler in patients with moderate asthma and in
patients with moderate to severe Chronic obstructive pulmonary disease (COPD).

Co-primary endpoints will be the area under the curve (AUCt) measured for plasma Fluticasone
propionate (pharmacokinetic) and the pharmacodynamic effects of Fluticasone propionate
(weighted mean serum cortisol over 0-12h) on the last day of each 10 day study treatment
period. Secondary endpoints will include the following pharmacokinetic parameters for both
fluticasone propionate and salmeterol: AUClast, AUC(0-t), Cmax, Cmin, tmax, ?z, and t1/2 as
well as the pharmacodynamic effects of salmeterol (pulse rate, blood pressure,
electrocardiogram [ECG], potassium and glucose) and Fluticasone propionate (urine cortisol
levels). Safety (adverse events and laboratory abnormalities) will also be assessed as a
secondary endpoint.

The study is a randomised, double blind, double dummy, four-period cross-over study.
Approximately 60 asthma or COPD patients will be randomised. Patients meeting eligibility
criteria will receive Fluticasone propionate/salmeterol 250/50mcg bid, from a capsule-based
inhaler and from a multi-dose dry powder inhaler for a period of 10 days each in a randomised
order. All patients will receive treatment from each device twice. To maintain the double
blind, each patient will receive active treatment and placebo at the same time from two
separate devices.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01494610
Trial related presentations / publications
Daley-Yates PT, Mehta R, Chan RH, Despa SX, Louey MD. Pharmacokinetics and pharmacodynamics of fluticasone propionate and salmeterol delivered as a combination dry powder from a capsule-based inhaler and a multidose inhaler in asthma and COPD patients. J Aerosol Med Pulm Drug Deliv. 2014 Aug;27(4):279-89. doi: 10.1089/jamp.2013.1040. Epub 2013 Sep 28.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
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Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01494610