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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02218723




Registration number
NCT02218723
Ethics application status
Date submitted
14/08/2014
Date registered
18/08/2014
Date last updated
24/07/2018

Titles & IDs
Public title
Pharmacokinetic Profile of Four Formulations of Fluticasone Furoate (FF) Using Unit Dose Dry Powder Inhaler (UD-DPI) Compared With FF ELLIPTA® Presentation
Scientific title
An Open-label, Randomised, Cross-over, Single Dose Study in Healthy Volunteers to Evaluate the Unit Dose Dry Powder Inhaler (UD-DPI) With Four Different Formulations for the Delivery of Fluticasone Furoate and to Compare the Pharmacokinetic Profile With the Fluticasone Furorate ELLIPTA Presentation
Secondary ID [1] 0 0
200939
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 - FF UD-DPI
Treatment: Drugs - FF ELLIPTA DPI

Active Comparator: Sequence ABECD - Subject will be administered treatment in sequence ABECD. Where, A: a single dose of FF [100 microgram (mcg) per blister from 0.6% blend] delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence BCADE - Subject will be administered treatment in sequence BCADE. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence CDBEA - Subject will be administered treatment in sequence CDBEA. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence DECAB - Subject will be administered treatment in sequence DECAB. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence EADBC - Subject will be administered treatment in sequence EADBC. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence DCEBA - Subject will be administered treatment in sequence DCEBA. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence EDACB - Subject will be administered treatment in sequence EDACB. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence AEBDC - Subject will be administered treatment in sequence AEBDC. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence BACED - Subject will be administered treatment in sequence BACED. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg

Active Comparator: Sequence CBDAE - Subject will be administered treatment in sequence CBDAE. Where, A: a single dose of FF (100mcg per blister from 0.6% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; B: a single dose of FF (80mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 320mcg; C: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 400mcg; D: a single dose of FF (140mcg per Blister from a 0.8% blend) delivered via the UD-DPI by inhalation of 4 Blisters giving a total dose of 560mcg; E: a single dose of FF (100mcg per Blister from a 0.8% blend) delivered via the ELLIPTA DPI by inhalation of 4 Blisters giving a total dose of 400mcg


Treatment: Drugs: FF UD-DPI
A blister containing a small quantity of powder comprising of a blend of FF (micronised) and excipient(s) will be administered using UD-DPI. It is available in following dosages: 80mcg/Blister (0.8% Blend); 100mcg/Blister (0.8% Blend); 140mcg/Blister (0.8% Blend); 100mcg/Blister (0.6% Blend)

Treatment: Drugs: FF ELLIPTA DPI
A blister strip contained within the ELLIPTA device. Each blister contains a small quantity of powder comprising of a blend of FF and excipient(s) in dose 100mcg/Blister (0.8% Blend)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AUC from time zero (pre-dose) to 24 hours (hr) (AUC [0-24hr]) and/ or AUC from time zero extrapolated to infinite time (AUC [0-infinity]) and/ or AUC from time zero to last time of quantifiable concentration (AUC [0-t]) - AUC (0-24h) and/or AUC(0-t) and/or AUC(0- infinity) will be measured at predose, 5 minutes (min), 10 min, 20 min, 30 min and 45 min, 1 hr, 1.5 hr, 2 hr, 3 hr,4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr and 48 hr
Timepoint [1] 0 0
Day 1, Day 2 and Day3 of each period
Secondary outcome [1] 0 0
Cmax - Cmax will be measured at predose, 5 min, 10 min, 20 min, 30 min and 45 min, 1 hr, 1.5 hr, 2 hr, 3 hr,4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr and 48 hr
Timepoint [1] 0 0
Day 1, Day 2 and Day3 of each period
Secondary outcome [2] 0 0
Time to Cmax (tmax) - Tmax will be measured at predose, 5 min, 10 min, 20 min, 30 min and 45 min, 1 hr, 1.5 hr, 2 hr, 3 hr,4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 36 hr and 48 hr
Timepoint [2] 0 0
Day 1, Day 2 and Day3 of each period
Secondary outcome [3] 0 0
Safety as assessed by adverse events (AE) - An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Timepoint [3] 0 0
Up to Week 13
Secondary outcome [4] 0 0
Safety as assessed by 12 Lead Electrocardiogram (ECG) Parameters - Single 12-lead ECGs will be measured in a semi-supine position at each timepoint during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT duration corrected
Timepoint [4] 0 0
Day 1 in each period
Secondary outcome [5] 0 0
Safety as assessed by Vital signs - Vital signs include temperature, systolic and diastolic blood pressure, heart rate
Timepoint [5] 0 0
Day 1, Day 3 in each period

Eligibility
Key inclusion criteria
- AGE- Between 18 and 65 years of age inclusive, at the time of signing the informed
consent

- TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY

- Healthy as determined by the investigator or medically qualified designee based on a
medical evaluation including medical history, physical examination, and laboratory
tests.

- A subject with a clinical abnormality or laboratory parameter(s) 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 in
consultation with the Medical Monitor if required agree and document that the finding
is unlikely to introduce additional risk factors and will not interfere with the study
procedures.

- WEIGHT-Body Weight >= 50 kilogram and BMI within the range 19.0 - 34.0 kilogram per
square metre (inclusive)

- SEX

- Male,

- Female subject : is eligible to participate if she is not pregnant [as confirmed by a
negative serum human chorionic gonadotrophin (hCG) test at screening or urine hCG
prior to dosing], not lactating, and at least one of the following conditions applies:

- Non-reproductive potential defined as: Pre-menopausal females with one of the
following: Documented tubal ligation, Documented hysteroscopic tubal occlusion
procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy,
Documented Bilateral Oophorectomy

- Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a
blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels
consistent with menopause (refer to laboratory reference ranges for confirmatory
levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is
in doubt will be required to use one of the highly effective 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 enrolment.

- Reproductive potential and agrees to follow one of the options listed below in the GSK
Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
Reproductive Potential (FRP) requirements from 30 days prior to the first dose of
study medication and until completion of the follow-up visit.

- GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
Reproductive Potential (FRP)

- This list does not apply to FRP with same sex partners, when this is their preferred
and usual lifestyle or for subjects who are and will continue to be abstinent from
penile-vaginal intercourse on a long term and persistent basis.

- Contraceptive subdermal implant that meets the SOP effectiveness criteria including a
<1% rate of failure per year, as stated in the product label

- Intrauterine device or intrauterine system that meets the SOP effectiveness criteria
including a <1% rate of failure per year, as stated in the product label

- Oral Contraceptive, either combined or progestogen alone

- Injectable progestogen

- Contraceptive vaginal ring

- Percutaneous contraceptive patches

- Male partner sterilization with documentation of azoospermia prior to the female
subject's entry into the study, and this male is the sole partner for that subject

- These allowed methods of contraception are only effective when used consistently,
correctly and in accordance with the product label. The investigator is responsible
for ensuring that subjects understand how to properly use these methods of
contraception.

- INFORMED CONSENT Capable of giving signed informed consent which includes compliance
with the requirements and restrictions listed in the consent form and in protocol.

- OTHER

- Capable of using the UD-DPI and the ELLIPTA DPI adequately after training

- Subjects who are current non-smokers, who have not used any tobacco products in the 6
month period preceding the screening visit, and have a pack history of <= 5 pack
years.

- Number of pack years = (number of cigarettes per day/20) x number of years smoked
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL

- Alanine transaminase (ALT) and bilirubin >1.5x Upper Limit of Normal (ULN) (isolated
bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin
<35%).

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

- Clinically significant abnormal ECG finding. Significant is defined as any finding
that, in the opinion of the investigator, would put the safety of the subject at risk
through participation.

- CONCOMITANT MEDICATIONS

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements within 7 days or 5 half-lives (whichever is longer) prior to the first
dose of study medication, or use of St. John's Wort within 14 days prior to the first
dose of study medication. By exception, the volunteer may take paracetamol (<=2
grams/day) any time during the study. However, the Investigator and GSK study team can
review medication on a case by case basis to determine if its use would compromise
subject safety or interfere with the study procedures or data interpretation

- RELEVANT HABITS

- History of regular alcohol consumption within 2 months of the study defined as:

- For Australian sites: An average weekly intake of >21 units for males or >14 units for
females. One unit (= standard drink) is equivalent to 10 g of alcohol: 270ml of full
strength beer (4.8%), 375mL of mid strength beer (3.5%), 470mL of light beer (2.7%),
250mL pre-mix full strength spirit (5%), 100mL of wine (13.5%) and 30mL of spirit
(40%).

- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
nicotine-containing products within 6 months prior to screening.

- An unwillingness to abstain from strenuous exercise starting 72 hours prior to each
dosing day

- An unwillingness to abstain from caffeine- and xantheine- containing products for 24
hours prior to dosing.

- Consumption of red wine, Seville oranges, grapefruit or grapefruit juice pummelos,
exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the
first dose of study medication.

- CONTRAINDICATIONS

- Drug Allergy:

- Any immediate or delayed hypersensitivity reaction to a corticosteroid (i.e.,
intranasal, inhaled, systemic therapy).

- Known or suspected sensitivity to the constituents of the DPI or (i.e., lactose or
magnesium stearate).

- Milk Protein Allergy: History of severe milk protein allergy.

- History of drug or other allergy that, in the opinion of the investigator or Medical
Monitor, contraindicates their participation.

- The subject has taken systemic, oral or depot corticosteroids less than 12 weeks
before the screening visit.

- The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before
the screening visit.

- DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA

- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
result at screening or within 3 months prior to first dose of study treatment. . For
potent immunosuppressive agents, subjects with presence of hepatitis B core antibody
(HBcAb) should also be excluded.

- A positive pre-study drug/alcohol screen.

- A positive test for HIV antibody.

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

- 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.

- The subject has a history of breathing problems in adult life (e.g. history of
asthmatic symptomatology). Screening lung function tests will be performed to confirm
normal lung function parameters Forced Expiratory Volume in 1 Second (FEV1) >=85%
predicted and FEV1/ Forced Vital capacity (FVC) ratio >=0.7).

- Subjects who have suffered a lower respiratory tract infection within 4 weeks of the
screening visit

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [2] 0 0
GSK Investigational Site - Adelaide
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5000 - Adelaide

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

Ethics approval
Ethics application status

Summary
Brief summary
This is an open-label, five- period, cross-over, randomized, single dose, single centre study
in healthy subjects. This is the second clinical study for the UD-DPI. This study will
ascertain whether the Pharmacokinetics (PK) systemic exposure [in terms of area under the
plasma concentration-time curve (AUC) and maximum observed plasma concentration (Cmax)] of FF
delivered via the UD-DPI is comparable to the systemic exposure of FF delivered via the
ELLIPTA Dry Powder Inhaler (DPI). For this reason four treatment doses consisting of three
dose strengths and 2 percentage blends will be assessed when delivered via the UD-DPI. This
study is designed to compare the pharmacokinetic profile of various doses and blends of FF
administered via UD-DPI and relative to FF administered via ELLIPTA DPI. Subjects will be
screened 28 days prior to study initiation. During each treatment period, subjects will be at
study site from evening prior to dosing until completion of the 48 hour post-dose PK sample
collection on Day 3. Minimum 7 days washout will be between treatments after completion of
all five treatments and the follow-up visit will be conducted 7-14 days post last dose.
Duration of study is 13 weeks. ELLIPTA is a registered trademark of the GSK group of
companies.
Trial website
https://clinicaltrials.gov/show/NCT02218723
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
Other publications