Pharmacokinetic and Pharmacodynamic (PK and PD) Study of... | NCT01494610

Description Module

Detailed Description

BACKGROUND This study will evaluate the comparative bioavailability of SERETIDE delivered via the established multi-dose powder inhaler ie DISKUS/Accuhaler and a new fluticasone propionate/salmeterol capsule-based inhaler. Both formulations will be delivered at the 250/50mcg (micrograms) twice daily (bid) dose strength.

STUDY RATIONALE The fluticasone propionate/salmeterol capsule-based inhaler has been developed for administration in both asthma and Chronic obstructive pulmonary disease (COPD) patients. Therefore, both disease populations are included in this study. The study will assess the performance of the two devices with respect to systemic exposure and pharmacodynamic effects. A replicated cross-over design (four period) was chosen. This design reduces subject numbers by about 50% compared to a standard 2-period cross-over design.

OBJECTIVES Primary Objective

-To compare the performance of fluticasone propionate/salmeterol administered in a capsule-based inhaler with the multi-dose dry powder inhaler by evaluating fluticasone propionate pharmacokinetic and pharmacodynamic endpoints.

Secondary Objectives

To compare the pharmacokinetic and pharmacodynamic effects of the salmeterol component of fluticasone propionate/salmeterol after administration from a capsule-based inhaler and from the multi-dose dry powder inhaler
To compare the safety and tolerability of fluticasone propionate/salmeterol after administration in a capsule-based inhaler with the multi-dose dry powder inhaler.

ENDPOINTS Primary Endpoints

Pharmacokinetic endpoint: AUCτ for fluticasone propionate (area under the plasma fluticasone propionate concentration-time curve over dosing interval) on the last day of each study treatment period (Day 10).
Pharmacodynamic endpoint: Weighted mean serum cortisol over 12h on the last day of each treatment period (Day 10).

Secondary Endpoints

Pharmacokinetic parameters (AUClast, AUC(0-t), Cmax, Cmin, tmax, λz, and t1/2 for fluticasone propionate and salmeterol) on the last day of each treatment period (Day 10).
Pharmacodynamic parameters:
Fluticasone propionate: Urine cortisol excretion (0-24h) and serum cortisol Cmin on the last day (Day 10) of each treatment period,
Salmeterol: pharmacodynamic parameters for pulse rate, blood pressure, electrocardiogram (ECG), plasma potassium and glucose (weighted mean 0-12h and Cmax/Cmin) on the last day (Day 10) of each treatment period
Safety and tolerability: Incidence of adverse events and laboratory abnormalities

STUDY DESIGN This is a randomised, four-period cross-over, double-blind, double-dummy study. Patients meeting eligibility criteria will receive fluticasone propionate/salmeterol 250/50 mcg bid from a capsule-based inhaler and from a multi-dose dry powder inhaler for 10 days per each treatment period in a randomised order. To maintain the double blind, each patient will receive both active treatment and placebo at the same time from two separate devices. Patients already on inhaled corticosteroid (ICS) monotherapy or combination treatment prior to randomization will stop their existing treatment and switch to treatment provided by the study-provided devices.

The study has been designed to compare the administration of fluticasone propionate/salmeterol from two inhalation devices, a capsule-based inhaler and a multi-dose dry powder inhaler. Fluticasone propionate/salmeterol administered via the multi-dose dry powder inhaler will be the reference product. Fluticasone propionate/salmeterol is being developed by GlaxoSmithKline (GSK) as a capsule-based inhaler for administration for the treatment of both asthma and COPD.

TREATMENT ASSIGNMENT Subjects will be assigned to one of two treatment sequences in accordance with the randomisation schedule Sequence ABBA (Periods 1 to 4): A: Fluticasone propionate/salmeterol from a multi-dose dry powder inhaler; B: Fluticasone propionate/salmeterol from a capsule-based inhaler; B: Fluticasone propionate/salmeterol from a capsule-based inhaler; A: Fluticasone propionate/salmeterol from a multi-dose dry powder inhaler Sequence BAAB (Periods 1 to 4): B: Fluticasone propionate/salmeterol from a capsule-based inhaler; A: Fluticasone propionate/salmeterol from a multi-dose dry powder inhaler; A: Fluticasone propionate/salmeterol from a multi-dose dry powder inhaler; B: Fluticasone propionate/salmeterol from a capsule-based inhaler.

Label	Type	Description	Intervention Names
SERETIDE Rotacaps	Experimental	Fluticasone propionate (250 micrograms [ug])/Salmeterol (50 ug) combination delivered in a capsule-based inhaler	Drug: SERETIDE Rotacaps
SERETIDE Diskus	Active Comparator	Fluticasone propionate (250 ug)/Salmeterol (50 ug) combination delivered in a multi-dose dry powder inhaler	Drug: SERETIDE Diskus
Placebo Rotacaps	Placebo Comparator	Placebo delivered in a capsule-based inhaler	Drug: SERETIDE Diskus
Placebo Diskus	Placebo Comparator	Placebo delivered in a multi-dose dry powder inhaler	Drug: SERETIDE Rotacaps

Name	Type	Description	Arm Group Labels	Other Names
SERETIDE Rotacaps	Drug	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.

Measure	Description	Time Frame
Mean Area Under the Concentration Time Curve Over the Dosing Period (AUC[0-tau]) for FP	Blood samples of participants (par.) with asthma and chronic obstructive pulmonary disease (COPD) were collected and analyzed for AUC(0-tau), a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (12 hours). Asthma is a disorder that causes the airways of the lungs to swell and narrow, leading to difficulty in breathing. COPD is a chronic lung disease with structural changes in lungs, leading to difficulty in breathing.	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
Weighted Mean Serum Cortisol (SC) Over 0 to 12 Hours Post Dose	Participants' blood samples were collected and analyzed for SC levels. Weighted mean SC levels are evaluted as a measure of the degree of cortisol suppression, allowing for the determination of whether differences in systemic exposure to the inhaled steroid component of two devices can be significant enough to result in the differences in the body's ability to release cortisol. Weighted means were derived by calculating the AUC over the 0-12 hour period, using the linear trapezoidal rule (statistical technique used for numerical analysis) and then dividing it by the actual time interval.	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

Measure	Description	Time Frame
Mean Plasma AUC(0-tau) and Plasma AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-tlast]) for Salmeterol	Blood samples of participants with asthma and COPD were collected and analyzed for AUC(0-tau) and AUC(0-tlast). AUC(0-tau) is a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (12 hours). AUC(0-tlast) is a measure of the plasma drug concentration from pre-dose to the last measurable concentration.

Eligibility Module

Eligibility 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 βhCG (β-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].

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Randwick	New South Wales	2031	Australia
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
24074143	Background	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.

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
114334	Statistical Analysis Plan	View IPD

ID	Title	Description
FG000	FP/Salmeterol 250/50 mcg: Sequence ABBA	Participants received fluticasone propionate (FP)/salmeterol 250/50 micrograms (mcg) twice daily via a capsule-based inhaler for two 10-day periods and via a multi-dose dry powder (MDPI) inhaler for two 10-day periods in a replicate crossover design. Participants were dosed approximately every 12 hours. Treatment was given in the sequence of ABBA in Periods 1, 2, 3, and 4 (with no washouts between periods), respectively. A, FP/salmeterol from an MDPI; B, FP/salmeterol from a capsule-based inhaler.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Area Under the Concentration Time Curve Over the Dosing Period (AUC[0-tau]) for FP

Blood samples of participants (par.) with asthma and chronic obstructive pulmonary disease (COPD) were collected and analyzed for AUC(0-tau), a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (12 hours). Asthma is a disorder that causes the airways of the lungs to swell and narrow, leading to difficulty in breathing. COPD is a chronic lung disease with structural changes in lungs, leading to difficulty in breathing.

Pharmacokinetic/pharmacodynamic (PK/PD) Population: all participants who received at least one dose of study medication, except for one who was identified as a full protocol violator. Participants with at least one non-missing value in the replicate observations were included.

Posted

Geometric Mean

95% Confidence Interval

Picogram hours per milliliter (pg*h/mL)

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts
Participants	OG00057 OG00157

Title

Denominators

Categories

Asthma + COPD; n=57, 57

Title	Measurements
	OG000376.9(337.0 to 421.6) OG001573.1(519.3 to 632.5)

Asthma; n=33, 33

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Ratio of adjusted geometric means	1.508			2-Sided	90	1.366	1.665			Data reflect Asthma + COPD participants. The ratio of adjusted geometric means is a comparision of treatment administered by the capsule-based inhaler and the MDPI.		Non-Inferiority or Equivalence	Estimates of within-par. coefficient of variation for AUC(0-tau) of FP and weighted mean (0-12 h) serum cortisol from previous studies showed that a sample size of 52 par. would have approximately 90% power to demonstrate biocomparability with respect to the two co-primary endpoints. The study was powered on the analysis of asthma and COPD par. as a combined group. A two one-sided t-test procedure with α=0.05 for each one-sided test was used. Biocomparability limits of 0.8 and 1.25 were used.

Primary

Weighted Mean Serum Cortisol (SC) Over 0 to 12 Hours Post Dose

Participants' blood samples were collected and analyzed for SC levels. Weighted mean SC levels are evaluted as a measure of the degree of cortisol suppression, allowing for the determination of whether differences in systemic exposure to the inhaled steroid component of two devices can be significant enough to result in the differences in the body's ability to release cortisol. Weighted means were derived by calculating the AUC over the 0-12 hour period, using the linear trapezoidal rule (statistical technique used for numerical analysis) and then dividing it by the actual time interval.

PK/PD Population

Posted

Geometric Mean

95% Confidence Interval

Nanomoles per liter (nmol/L)

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Plasma AUC(0-tau) and Plasma AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC[0-tlast]) for Salmeterol

Blood samples of participants with asthma and COPD were collected and analyzed for AUC(0-tau) and AUC(0-tlast). AUC(0-tau) is a measure of the amount of drug available at target tissue (in plasma) for a fixed dosing interval (12 hours). AUC(0-tlast) is a measure of the plasma drug concentration from pre-dose to the last measurable concentration.

PK/PD Population

Posted

Geometric Mean

95% Confidence Interval

pg*h/mL

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean AUC(0-tlast) for FP

Blood samples of participants with asthma and COPD were collected and analyzed for AUC(0-tlast). AUC(0-tlast) is a measure of the plasma drug concentration from pre-dose to the last measurable concentration.

PK/PD Population

Posted

Geometric Mean

95% Confidence Interval

pg*h/mL

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts
Participants

Secondary

Mean Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of FP

Blood samples of participants with asthma and COPD were collected and analyzed for Cmax and Cmin of FP in the blood. Cmax and Cmin are used to estimate the time at which the activity of the drug will be at its maximum and minimum, respectively.

PK/PD Population

Posted

Geometric Mean

95% Confidence Interval

Picograms per milliliter (pg/mL)

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts

Secondary

Mean Terminal Phase Half-life (t1/2) for FP

Blood samples of participants were collected for evaluating t1/2. The t1/2 is the time required for the plasma/blood concentration of the drug to decrease by 50% after the false equilibrium of distribution has been reached.

PK/PD Population. Only those participants contributing data at the indicated time points were analyzed.

Posted

Geometric Mean

95% Confidence Interval

hours

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts

Secondary

Time of Occurrence of Cmax (Tmax) for FP

Blood samples of participants were collected for evaluating Tmax. Tmax is a measure of the time required to reach the maximum concentration of the drug.

PK/PD Population

Posted

Median

Full Range

hours

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts
Participants

Secondary

Mean Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) for Salmeterol

Blood samples of participants with asthma and COPD were collected and analyzed for Cmax and Cmin of Salmeterol in the blood. Cmax and Cmin are used to estimate the time at which the activity of the drug will be at its maximum and minimum.

PK/PD Population

Posted

Geometric Mean

95% Confidence Interval

pg/mL

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts

Secondary

Mean Terminal Phase Half-life (t1/2) for Salmeterol

Blood samples of participants were collected for evaluating t1/2. t1/2 is the time required for the plasma/blood concentration of the drug to decrease by 50% after the false equilibrium of distribution has been reached.

PK/PD Population. Only those participants contributing data at the indicated time points were analyzed.

Posted

Geometric Mean

95% Confidence Interval

hours

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts

Secondary

Tmax for Salmeterol

Blood samples of participants were collected for evaluating Tmax. Tmax is a measure of the time required to reach the maximum concentration of the drug.

PK/PD Population

Posted

Median

Full Range

hours

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts
Participants

Secondary

Mean Urine Cortisol Excretion Over 0 to 24 Hours Post Dose for FP

Urine samples of participants were collected to evaluate urine cortisol excretion over 0-24 hours post treatment dose. A 24-hour urine cortisol sample was used to measure the total amount of cortisol excreted in urine in 24 hours. Any differences in systemic exposure as a result of the absorbed steroid component of the two differing inhaled devices should also result in differences in the amount of cortisol excreted in the urine.

PK/PD Population

Posted

Geometric Mean

95% Confidence Interval

nmol

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Serum Cortisol Minimum (Cmin) for FP

Blood samples of participants were collected for the evaluation of minimum serum cortisol. Any differences in systemic exposure as a result of the absorbed steroid component of the two differing inhaled devices should also result in differences in serum cortisol concentrations.

PK/PD Population

Posted

Geometric Mean

95% Confidence Interval

nmol/L

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts
Participants

Secondary

Weighted Mean Over 0 to 4 Hours Post Dose of Heart Rate for Salmeterol

The heart rate (number of heartbeats per unit of time, typically expressed as beats per minute [bpm]) of the participants was monitored for evaluating the weighted mean over the course of 0 to 4 hours post dose. The Capsule-MDPI difference for heart rate was calculated for each participant, and the weighted mean value from the time of the morning dose on Day 10 to 4 hours post dose was calculated. The weighted mean was calculated by using all values at the indicated timepoint contributing to the calculation of the mean but with different weightage.

PK/PD Population

Posted

Mean

Standard Deviation

bpm

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean of Maximum Heart Rate Over 0 to 4 Hours Post Dose for Salmeterol

The maximum observed value of heart rate was measured from the time of the morning dose on Day 10 to 4 hours post dose.

PK/PD Population

Posted

Mean

Standard Deviation

bpm

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts
Participants

Secondary

Minimum Diastolic Blood Pressure (DBP), Maximum Systolic Blood Pressure (SBP), and Weighted Mean for DBP and SBP Over 0 to 4 Hours Post Dose

The diastolic and systolic blood pressure of the participants was measured. The maximum and minimum observed values from the time of the morning dose on Day 10 to 4 hours post dose were measured for SBP and DBP. The weighted mean value from the time of the morning dose on Day 10 to 4 hours post dose was calculated. Weighted mean was calculated by using all values of DBP and SBP at the indicated timepoint contributing to the calculation of the mean but with different weightage.

PK/PD Population

Posted

Mean

Standard Deviation

millimeters of mercury (mmHg)

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

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])

The electrocardiogram (ECG) of the participants was taken, and the maximum and weighted mean of QTc(B) and QTc(F) was measured. Weighted mean was calculated by using all values of QTc(B) and QTc(F) at the indicated timepoint contributing to the calculation of the mean but with different weightage. The ECG helps in the assessment of the condition of the heart. The QT interval gives the measure of the heart rate, and the cQT interval gives the corrected value.

PK/PD Population

Posted

Mean

Standard Deviation

Milliseconds (msec)

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Weighted Mean Over 0 to 4 Hours Post Dose of Plasma Potassium and Minimum (Min) Plasma Potassium

Blood samples of participants were collected for the evaluation of weighted mean over 0 to 4 hours post dose and the minimum plasma potassium level. Weighted mean was calculated by using all values of plasma potassium at the indicated timepoint contributing to the calculation of the mean but with different weightage.

Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

Millimoles per liter (mmol/L)

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Weighted Mean Over 0 to 4 Hours Post Dose and Maximum Plasma Glucose

Blood samples of participants were collected for the evaluation of weighted mean over 0 to 4 hours post dose and the maximum plasma glucose level. Weighted mean was calculated by using all values of plasma glucose at the indicated timepoint contributing to the calculation of the mean but with different weightage.

PK/PD Population

Posted

Mean

Standard Deviation

mmol/L

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts

Secondary

Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cell (WBC) Count

Blood samples of participants were collected for the evaluation of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, and WBC count. Data are reported for the first (1st) and second (2nd) administration (admin) of FP/salmeterol via MDPI or capsule-based inhaler. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population: all participants who received at least one dose of study medication. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

Giga (10^9) cells/L

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Hemoglobin and Mean Corpuscular Hemoglobin (MCH) Concentration

Blood samples of participants were collected for the evaluation of mean hemoglobin (mean level of hemoglobin in the whole blood sample) and MCH concentration. The MCH concentration is the average concentration of hemoglobin in a red blood cell. Hemoglobin is the red pigment in the blood, and it is reponsible for carrying oxygen. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

Grams per liter (g/L)

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Red Blood Cell (RBC) Count and Reticulocytes

Blood samples of participants were collected for the evaluation of RBC and reticulocytes count. Reticulocytes are immature red blood cells. Normally, about 1% to 2% of the red blood cells in the blood are reticulocytes. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

Trillion (10^12) cells/L

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Corpuscule Hemoglobin (MCH)

Blood samples of participants were collected for the evaluation of MCH. MCH is the average mass or amount of hemoglobin per red blood cell in a sample of blood. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subject Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

picograms (pg)/cell

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Corpuscle Volume (MCV)

Blood samples of participants were collected for the evaluation of MCV. MCV is a measure of the average red blood cell size that is reported as part of a standard complete blood count. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

Femtoliters (fL; 10^-15 L)/cell

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Hematocrit

Blood samples of participants were collected for the evaluation of hematocrit. The hematocrit is the percentage of the RBCs in the blood. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

percentage of RBCs

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Albumin and Total Protein

The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

g/L

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts

Secondary

Mean Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amio Transferase (AST), and Gama Glutamyl Transferase (GGT)

Blood samples of participants were collected for the evaluation of AP, ALT, AST, and GGT. All of these parameters are measured to help assess the condition of the liver. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

International units per liter (IU/L)

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Direct Bilirubin (DB), Total Bilirubin (TB), Creatinine, and Uric Acid

Blood samples of participants were collected for the evaluation of DP, TB, creatinine, and uric acid. DB and TB are measures that help assess the condition of the liver, and creatinine and uric acid are measures that help assess the condition of the kidneys. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

Micromoles per liter (µmol/L)

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Mean Calcium, Chloride, Glucose, Potassium, Sodium, Carbon Dioxide (CO2) Content/Bicarbonate (Bicar), and Urea/Blood Urea Nitrogen (BUN)

Blood samples of participants were collected for the evaluation of calcium, chloride, glucose, potassium, sodium, carbon dioxide (CO2) content/bicarbonate, and urea/BUN. All of these parameters are measured to help assess the condition of the kidneys. The timing of the first and second administrations depended on the randomization schedule. If the treatment sequence received was "ABBA," then Days 10 and 40, respectively, correspond to the first and second administrations for treatment A.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Mean

Standard Deviation

µmol/L

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

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Secondary

Number of Participants With an Adverse Event (AE)

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

All Subjects Population. Out of the total population, 34 participants had asthma and 26 participants had COPD. Only those participants contributing data at the indicated time points were analyzed.

Posted

Number

participants

Randomization (Day 1) up to Follow-up (Days 47-50)

ID	Title	Description
OG000	FP/Salmeterol From MDPI	Fluticasone propionate (FP)/salmeterol combination was administered as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for two 10-day periods
OG001	FP/Salmeterol From Capsule-based Inhaler	Fluticasone propionate/salmeterol combination was administered as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for two 10-day periods.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FP/Salmeterol From MDPI 1st Administration (Admin), Asthma	Fluticasone propionate (FP)/salmeterol combination was administered to participants with asthma as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for a 10-day period.	0	33	13	33
EG001	FP/Salmeterol From MDPI 2nd Admin, Asthma	Fluticasone propionate (FP)/salmeterol combination was administered to particiapants with asthma as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for a 10-day period.	0	31	12	31
EG002	FP/Salmeterol From Capsule-based Inhaler 1st Admin, Asthma	Fluticasone propionate (FP)/salmeterol combination was administered to participants with asthma as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for a 10-day period.	0	34	13	34
EG003	FP/Salmeterol From Capsule-based Inhaler 2nd Admin, Asthma	Fluticasone propionate (FP)/salmeterol combination was administered to participants with asthma as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for a 10-day period.	1	33	15	33
EG004	FP/Salmeterol From MDPI 1st Admin, COPD	Fluticasone propionate (FP)/salmeterol combination was administered to participants with COPD as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for a 10-day period.	0	26	14	26
EG005	FP/Salmeterol From MDPI 2nd Admin, COPD	Fluticasone propionate (FP)/salmeterol combination was administered to participants with COPD as a powder in blister in the dose of 250/50 micrograms (mcg) twice daily (BID) via a multi-dose dry powder inhaler (MDPI) for a 10-day period.	0	25	9	25
EG006	FP/Salmeterol From Capsule-based Inhaler 1st Admin, COPD	Fluticasone propionate (FP)/salmeterol combination was administered to participants with COPD as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for a 10-day period.	0	25	11	25
EG007	FP/Salmeterol From Capsule-based Inhaler 2nd Admin, COPD	Fluticasone propionate (FP)/salmeterol combination was administered to participants with COPD as a powder in capsule in the dose of 250/50 mcg BID via a capsule-based inhaler for a 10-day period.	0	25	11	25

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0008 affected33 at risk EG0017 affected31 at risk EG00210 affected34 at risk EG00310 affected33 at risk EG0045 affected26 at risk EG0055 affected25 at risk EG0062 affected25 at risk EG0073 affected25 at risk
Migraine	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0011 affected31 at risk EG0021 affected34 at risk EG003
Presyncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0002 affected33 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Vaginal infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Viral infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Labyrinthitis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0002 affected33 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0012 affected31 at risk EG0020 affected34 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Hemorrhoids	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Gastroesophageal reflux disease	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Tooth disorder	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0011 affected31 at risk EG0020 affected34 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA	Systematic Assessment	EG0001 affected33 at risk EG0012 affected31 at risk EG0020 affected34 at risk EG003
Allergy to arthropod bite	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Food intolerance	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0021 affected34 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Malaise	General disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Vertigo positional	Ear and labyrinth disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected33 at risk EG0010 affected31 at risk EG0020 affected34 at risk EG003

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D012149	Restraint, Physical
D001800	Blood Specimen Collection
D014554	Urination

ID	Term
D032763	Behavior Control
D013812	Therapeutics
D007103	Immobilization
D008919	Investigative Techniques
D013048	Specimen Handling
D019411	Clinical Laboratory Techniques
D019937	Diagnostic Techniques and Procedures
D003933	Diagnosis
D011677	Punctures
D013514	Surgical Procedures, Operative
D014553	Urinary Tract Physiological Phenomena
D012101	Reproductive and Urinary Physiological Phenomena