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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/NCT02064504




Registration number
NCT02064504
Ethics application status
Date submitted
13/02/2014
Date registered
17/02/2014
Date last updated
15/05/2017

Titles & IDs
Public title
Study to Determine the Pharmacokinetics of GSK961081 and Fluticasone Furoate When Administered Alone or in Combination
Scientific title
An Open Label, Randomised, Six-way Crossover, Single Dose Study to Determine the Pharmacokinetics of GSK961081 and Fluticasone Furoate When Administered Alone or in Combination
Secondary ID [1] 0 0
201010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK961081
Treatment: Drugs - Fluticasone furoate

Experimental: Sequence 1 - Participants will receive the study treatment in the following order: ABFCED in each period (one per period). Where A=GSK961081 administered from DISKUS, B=GSK961081 Single strip (SS) administered from DPI, C=GSK961081 Dual Strip (DS) administered from DPI with a filled (lactose) second strip (DS configuration), D=GSK961081/fluticasone furoate (GSK961081/FF) administered from DPI (GSK961081 higher dose), E=FF DS administered from DPI with a filled (lactose) second strip (dual strip configuration), F=GSK961081/FF administered from DPI (GSK961081 lower dose).

Experimental: Sequence 2 - Participants will receive the study treatment in the following order: BCADFE in each period (one per period)

Experimental: Sequence 3 - Participants will receive the study treatment in the following order: CDBEAF in each period (one per period)

Experimental: Sequence 4 - Participants will receive the study treatment in the following order: DECFBA in each period (one per period)

Experimental: Sequence 5 - Participants will receive the study treatment in the following order: EFDACB in each period (one per period)

Experimental: Sequence 6 - Participants will receive the study treatment in the following order: FAEBDC in each period (one per period)


Treatment: Drugs: GSK961081
Dry white to off white powder

Treatment: Drugs: Fluticasone furoate
Dry white powder
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
GSK961081 AUC(0-t')
Timepoint [1] 0 0
Pre dose, 5 minutes (min), 15 min, 30 min, 45 min, 1 hour (h), 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period
Secondary outcome [1] 0 0
Cmax
Timepoint [1] 0 0
Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period
Secondary outcome [2] 0 0
AUC(0-t') and Cmax following single and dual strip administration of GSK961081
Timepoint [2] 0 0
Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period
Secondary outcome [3] 0 0
AUC(0-t') and Cmax following concurrent administration of GSK961081 and fluticasone furoate
Timepoint [3] 0 0
Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period
Secondary outcome [4] 0 0
Fluticasone furoate AUC(0-t') and Cmax
Timepoint [4] 0 0
Pre dose, 5 min, 15 min, 30 min, 45 min, 1 h, 2 h, 4 h, 6 h, 8 h, 10 h and 12 h for each treatment period
Secondary outcome [5] 0 0
Number of participants with Adverse Events
Timepoint [5] 0 0
Up to 12 Weeks

Eligibility
Key inclusion criteria
- Male/females aged between 18 and 64 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 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
determines that the finding is unlikely to introduce additional risk factors and will
not interfere with the study procedures.

- Body mass index (BMI) within the range 18 to 29.0 kilogram (kg)/meter (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 (FSH) greater than 40 MlU/mL and
estradiol less than 40 picogram (pg)/mL (less than 147 pmol/L) is confirmatory. Females on
hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required
to use 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 2-4 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 urine hCG test prior to dosing AND 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 for 5
terminal half-lives after the end of the study (i.e. until after the follow-up visit is
complete).

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 (ALT), alkaline phosphatase and bilirubin less than or equal
to 1.5x upper limit of normal (ULN) (isolated bilirubin greater than 1.5xULN is
acceptable if bilirubin is fractionated and direct bilirubin less than 35%).

- Forced Expiratory Volume in 1 second (FEV1) greater than or equal to 85% predicted and
a FEV1/ Forced Vital capacity (FVC) ratio greater than or equal to 0.7

- Based on single or averaged QTc values of triplicate Electrocardiograms (ECGs)
obtained over a brief recording period:

QT duration corrected for heart rate by Fridericia's formula (QTcF) less than 450
millisecond.
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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 greater than 21 units for males or greater than 14 units for
females. In Australia one unit (= standard drink) is equivalent to 10 gram of alcohol: 270
mL of full strength beer (4.8%), 375 mL 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.

- Urinary cotinine/ Breath carbon monoxide (CO) levels indicative of smoking or history
or regular use of tobacco- or nicotine-containing products within 6 months prior to
screening and a pack year history of </=10 pack years.

- A positive pre-study drug/alcohol screen.

- A positive test for Human Immunodeficiency Virus (HIV) antibody.

- 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
19/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/05/2014
Sample size
Target
Accrual to date
Final
48
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
GSK961081 is a novel bifunctional molecule that combines muscarinic antagonism and
beta2-agonism in a single molecule and is in development for the treatment of chronic
obstructive pulmonary disease (COPD). This is a randomised, open-label, six-way crossover,
single dose study. This study evaluates the drug delivery and systemic pharmacokinetics of
GSK961081 following concurrent administration of GSK961081 and fluticasone furoate via dry
powder inhaler (DPI) in comparison to GSK961081 DISKUS. There will be six treatment periods
and 7 days washout period in the study. Subjects will attend the unit in the morning for
dosing and will be resident until 12 hours post administration. All subjects will receive six
treatments.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02064504
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/NCT02064504