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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/NCT01890863




Registration number
NCT01890863
Ethics application status
Date submitted
27/06/2013
Date registered
2/07/2013
Date last updated
19/06/2018

Titles & IDs
Public title
ROTAHALER Device Optimization Study
Scientific title
An Open-Label, Randomised, Two Treatment, Four-Way Cross-Over (Replicate Design), Two Sequence, Repeat Dose, Single Centre Study in Healthy Volunteers to Compare the Pharmacokinetics of Fluticasone Propionate/Salmeterol (100/50 mcg) Delivered Via the Low Airflow Resistance ROTAHALER Inhaler Relative to Fluticasone Propionate/Salmeterol (100/50 mcg) Delivered Via the DISKUS Inhaler
Secondary ID [1] 0 0
200260
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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fluticasone Propionate / Salmeterol Xinafoate DISKUS
Treatment: Drugs - Fluticasone Propionate / Salmeterol Xinafoate ROTACAP

Experimental: Sequence 1 - Subjects will receive treatment A and B in following sequence in four treatment periods (one treatment per period): ABBA, where treatment A is 7 doses of FSC (100/50 mcg) delivered via the Ddpi and treatment B is 7 doses of FSC (100/50mcg) delivered via the Rdpi. Subjects will be dosed twice daily for 3 days and once on the fourth day in the morning (a single inhalation of 100/50mcg per dose).

Experimental: Sequence 2 - Subjects will receive treatment A and B in following sequence in four treatment periods (one treatment per period): BAAB, where treatment A is 7 doses of FSC (100/50 mcg) delivered via the Ddpi and treatment B is 7 doses of FSC (100/50mcg) delivered via the Rdpi. Subjects will be dosed twice daily for 3 days and once on the fourth day in the morning (a single inhalation of 100/50mcg per dose).


Treatment: Drugs: Fluticasone Propionate / Salmeterol Xinafoate DISKUS
Fluticasone propionate and salmeterol xinafoate combination as a dry powder inhaler for oral inhalation with unit dose strength of 100/50 mcg (available in blister pack) administered via DISKUS (Ddpi) device.

Treatment: Drugs: Fluticasone Propionate / Salmeterol Xinafoate ROTACAP
Fluticasone propionate and salmeterol xinafoate combination as a dry powder inhaler for oral inhalation with unit dose strength of 100/50 mcg (available in blister pack) administered via ROTAHALER (Rdpi) device.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of PK parameters of FSC delivered via the Rdpi relative to FSC delivered via the Ddpi
Timepoint [1] 0 0
PK samples will be collected at pre-dose, 5 minutes (mins), 10 mins, 30 mins, 1, 2, 4, 8, 10, and 12 hours post dose on Day 4 of each treatment period.
Secondary outcome [1] 0 0
Composite of PK parameters of FSC delivered via the Rdpi relative to FSC delivered via the Ddpi
Timepoint [1] 0 0
PK samples will be collected at pre-dose, 5 minutes (mins), 10 mins, 30 mins, 1, 2, 4, 8, 10, and 12 hours post dose on Day 4 of each treatment period.
Secondary outcome [2] 0 0
Number of participants with adverse events (AEs) as measure of safety and tolerability.
Timepoint [2] 0 0
35 days.
Secondary outcome [3] 0 0
Laboratory parameters as a measure of safety and tolerability.
Timepoint [3] 0 0
35 days
Secondary outcome [4] 0 0
Vital sign measurement as measure of safety and tolerability.
Timepoint [4] 0 0
35 days.

Eligibility
Key inclusion criteria
Inclusion Criteria

- Males and females aged between 18 and 65 years of age inclusive, at the time of
signing the informed consent.

- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring. A subject with a clinical abnormality or laboratory parameters
which is/are not specifically listed in the inclusion or exclusion criteria, outside
the reference range for the population being studied may be included only if the
Investigator determines that the finding is unlikely to introduce additional risk
factors and will not interfere with the study procedures.

- Body mass index within the range 18 to 35 kilograms/meter squared (m^2) (inclusive).

- A female subject is eligible to participate if she is of:

Non-childbearing potential defined as pre-menopausal females with a documented tubal
ligation or hysterectomy (for this definition, "documented" refers to the outcome of the
investigator's/designee's review of the subject's medical history for study eligibility, as
obtained via a verbal interview with the subject or from the subject's medical records); or
postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a
blood sample with simultaneous follicle stimulating hormone > 40 milli international
unit/mililiter [mL] and estradiol < 40 picogram/mL [<147 picomoles/liter] is confirmatory.
Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will
be required to use one of the contraception methods if they wish to continue their HRT
during the study. Otherwise, they must discontinue HRT to allow confirmation of
post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4
weeks will elapse between the cessation of therapy and the blood draw; this interval
depends on the type and dosage of HRT. Following confirmation of their post-menopausal
status, they can resume use of HRT during the study without use of a contraceptive method.

Child-bearing potential with negative pregnancy test as determined by serum human chorionic
gonadotropin (hCG) test at screening or prior to dosing.

Agrees to use one of the contraception methods for an appropriate period of time (as
determined by the product label or investigator) prior to the start of dosing to
sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to
use contraception until 2 days post-last dose.

OR has only same-sex partners, when this is her preferred and usual lifestyle.

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

- Alanine aminotransferase, alkaline phosphatase and bilirubin <= 1.5xupper limit of
normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated
and direct bilirubin <35 %).

- Based on single or averaged QT interval corrected (QTc) values of triplicate
electrocardiograms (ECGs) obtained over a brief recording period: QT duration
corrected for heart rate by Fridericia's formula (QTcF)<450 millisecond (msec), and QT
duration corrected for heart rate by Bazett's formula (QTcB)<480 msec in subjects with
Bundle Branch Block.
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria

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

- History of regular alcohol consumption within 6 months of the study defined as: An
average weekly intake of >21 units for males or >14 units for females. In Australia
one unit (= standard drink) is equivalent to 10 grams of alcohol: 270 mL of full
strength beer (4.8%), 375mL of mid strength beer (3.5%), 470 mL of light beer (2.7%),
250 mL pre-mix full strength spirit (5%), 100 mL of wine (13.5%) and 30 mL of spirit
(40%)

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation.

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

- A positive pre-study drug/alcohol screen.

- A positive test for human immuno virus antibody.

- Pregnant females as determined by positive serum hCG test at screening or prior to
dosing.

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

- Lactating females.

- 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.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
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
5/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2013
Sample size
Target
Accrual to date
Final
36
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

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

Ethics approval
Ethics application status

Summary
Brief summary
This study will compare the pharmacokinetic (PK) of Fluticasone Propionate/Salmeterol
combination (FSC) 100/50 micrograms (mcg) delivered via the capsule-based inhaler (Rdpi)
relative to FSC 100/50 mcg delivered via the multi-dose dry powder inhaler (Ddpi) to
establish whether the Rdpi inhaler has exposure (in terms of fluticasone propionate area
under time concentration curve [AUC] and Salmeterol maximum concentration [Cmax]) no greater
than 1.2500 compared to the Ddpi, sufficient to allow progression to Phase 3. This study will
enroll 36 healthy adult male and female subjects and each subject will be allocated to one of
two sequences and will participate in four treatment periods, receiving each of the
treatments twice.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01890863
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01890863