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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/NCT01984086




Registration number
NCT01984086
Ethics application status
Date submitted
7/11/2013
Date registered
14/11/2013
Date last updated
19/06/2018

Titles & IDs
Public title
Study to Evaluate the Pharmacokinetic Profile of Salbutamol Delivered by Unit Dose Dry Powder Inhaler (UD-DPI) Compared to the Diskus and Metered Dose Inhaler (MDI) in Healthy Volunteers.
Scientific title
An Open-label, Randomised, Cross-over, Two Cohort, Single Dose Study in Healthy Volunteers to Evaluate the Unit Dose Dry Powder Inhaler (UD-DPI) for the Delivery of Salbutamol and to Compare the Pharmacokinetic Profile With the MDI and Diskus Presentations.
Secondary ID [1] 0 0
200921
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 - Salbutamol Sulphate 150mcg UD-DPI Blister(1.6% blend)
Treatment: Drugs - Salbutamol Sulphate 200mcg UD-DPI Blister(1.6% blend)
Treatment: Drugs - Salbutamol Sulphate 250mcg UD-DPI Blister(1.6% blend)
Treatment: Drugs - Salbutamol Sulphate 200mcg UD-DPI Blister(1% blend)
Treatment: Drugs - Salbutamol Diskus 200mcg Blister
Treatment: Drugs - Salbutamol MDI 100mcg
Treatment: Drugs - Salbutamol Sulphate UD-DPI Blister (selected from Part A)
Treatment: Drugs - Salbutamol Sulphate 250mcg UD-DPI Blister (selected from Part A)
Treatment: Drugs - Salbutamol Diskus 200mcg Blister without activated charcoal
Treatment: Drugs - Salbutamol Diskus 200mcg Blister with activated charcoal
Treatment: Drugs - Salbutamol MDI 100mcg without activated charcoal
Treatment: Drugs - Salbutamol MDI 100mcg with activated charcoal

Experimental: Part A - Subjects will receive following six treatments each in six period, with a 3-days minimum wash-out period, between each treatment period: 1) Single dose (SD) salbutamol (200mcg per blister from 1.6% blend) delivered via the UD-DPI by inhalation of 3 Blisters (BTR) giving a total dose of 600mcg; 2) SD salbutamol sulphate (200mcg per BTR from a 1.0% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 600mcg; 3) SD salbutamol (150mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 450mcg; 4) SD salbutamol (250mcg per BTR from a 1.6% blend) delivered via the UD-DPI by inhalation of 3 BTR giving a total dose of 750mcg; 5) SD of salbutamol (200mcg per BTR) delivered via the Diskus by inhalation of 3 BTR giving a total dose of 600mcg; 6) SD salbutamol (100mcg per actuation) delivered via the MDI giving a total dose of 600mcg

Experimental: Part B - Prior to the start of Part B, a decision will be made regarding the UD-DPI products to be used in Part B. Subjects will receive following 6 treatments each in 6 period, with a 3-days minimum wash-out period, between each treatment period: 1) SD salbutamol (selected from Part A) delivered via the UD-DPI without activated charcoal (AC) by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 2) SD salbutamol (selected from Part A) delivered via the UD-DPI with AC by inhalation of 3 BTR (total dose dependant on UD-DPI formulation chosen); 3) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus without AC (total dose 600mcg); 4) SD salbutamol by inhalation of 3 BTR (200mcg per BTR) delivered via the Diskus with AC (total dose 600mcg); 5) SD salbutamol 6 inhalations (100mcg) delivered via the MDI without AC (total dose 600mcg); 6) SD salbutamol 6 inhalations (100mcg) delivered via the MDI with AC (total dose 600mcg)


Treatment: Drugs: Salbutamol Sulphate 150mcg UD-DPI Blister(1.6% blend)
Salbutamol Sulphate 150mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients

Treatment: Drugs: Salbutamol Sulphate 200mcg UD-DPI Blister(1.6% blend)
Salbutamol Sulphate 200mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients

Treatment: Drugs: Salbutamol Sulphate 250mcg UD-DPI Blister(1.6% blend)
Salbutamol Sulphate 250mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients

Treatment: Drugs: Salbutamol Sulphate 200mcg UD-DPI Blister(1% blend)
Salbutamol Sulphate 200mcg UD-DPI will be supplied as blister containing a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients

Treatment: Drugs: Salbutamol Diskus 200mcg Blister
Salbutamol Diskus 200mcg will be supplied as blister strip contained within the Diskus device. Each blister contains a small quantity of powder comprising of a blend of salbutamol sulphate (micronized) and excipients

Treatment: Drugs: Salbutamol MDI 100mcg
Salbutamol MDI 100mcg will be supplied as formulation of salbutamol sulphate (micronized) in propellant contained within the pressurised MDI device

Treatment: Drugs: Salbutamol Sulphate UD-DPI Blister (selected from Part A)
Formulation will be determined depending on the outcome of Part A.

Treatment: Drugs: Salbutamol Sulphate 250mcg UD-DPI Blister (selected from Part A)
Formulation will be determined depending on the outcome of Part A.

Treatment: Drugs: Salbutamol Diskus 200mcg Blister without activated charcoal
Formulation will be determined depending on the outcome of Part A.

Treatment: Drugs: Salbutamol Diskus 200mcg Blister with activated charcoal
Formulation will be determined depending on the outcome of Part A.

Treatment: Drugs: Salbutamol MDI 100mcg without activated charcoal
Formulation will be determined depending on the outcome of Part A.

Treatment: Drugs: Salbutamol MDI 100mcg with activated charcoal
Formulation will be determined depending on the outcome of Part A.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Pharmacokinetics parameters of single doses of salbutamol in healthy subjects delivered via the UD-DPI device, using a range of doses and blends, and to compare to MDI and Diskus
Timepoint [1] 0 0
Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Primary outcome [2] 0 0
Part B: Pharmacokinetics parameters of salbutamol in healthy subjects delivered via UD-DPI versus Diskus and/or MDI with charcoal blockade.
Timepoint [2] 0 0
Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Secondary outcome [1] 0 0
Part A: Pharmacokinetic parameters following single doses of salbutamol and different blends of salbutamol in healthy subjects delivered via UD-DPI
Timepoint [1] 0 0
Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Secondary outcome [2] 0 0
Part B: Pharmacokinetic parameters following single doses of salbutamol in healthy subjects delivered via UD-DPI , MDI and Diskus with/ and without charcoal
Timepoint [2] 0 0
Day 1 of each treatment period (Pre dose and 0 hr, 2 minute [min], 5 min, 10 min, 20 min, 30 min, 45 min, 1hr, 1.5 hr, 2hr, 4 hr, 6 hr, 8 hr, 10 hr and 12 hr post dose)
Secondary outcome [3] 0 0
Part A and B: Number of subjects with adverse events (AEs)
Timepoint [3] 0 0
Up to 14 days after the last dose of study treatment.
Secondary outcome [4] 0 0
Part A and B: Safety and tolerability of salbutamol, as assessed vital signs
Timepoint [4] 0 0
Day 1 of each treatment period
Secondary outcome [5] 0 0
Part A and B: Safety and tolerability of salbutamol, as assessed by 12-lead electrocardiogram (ECG) parameters
Timepoint [5] 0 0
Day 1 of each treatment period

Eligibility
Key inclusion criteria
Inclusion Criteria

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

- Body weight >=50 kg and body mass index within the range 19.0 - 34.0 kilogram per
square meter (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) >40
milli-international units per milliliter (MlU/mL) and estradiol < 40 picograms per
milliliter (pg/mL) (<147 picomole per 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 in listed in protocol 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
prior to dosing AND; Agrees to use one of the contraception methods listed in protocol
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 follow-up; 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

- 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 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 agree and document that the finding is unlikely to introduce additional
risk factors and will not interfere with the study procedures.

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

- Based on single or averaged corrected QT interval (QTc) values of triplicate ECGs
obtained over a brief recording period: QTcF <450 milliseconds.

- Current non-smokers who have not used any tobacco- containing products within 3 months
of screening and with a total pack year history of <=10 pack years [number of pack
years = (number of cigarettes per day / 20) x number of years smoked].

- Able to use all medical device products included in the study adequately after
training

Part B

- Able to tolerate the charcoal block at screening
Minimum age
18 Years
Maximum age
65 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 sensitivity to any of the study medications, or components thereof
(including milk protein allergy) 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 breath carbon monoxide test or urine drug or breath alcohol
screen.

- A positive test for HIV antibody.

- Screening PR interval outside the range 120 to 240msec; or an ECG that is not suitable
for QT measurements (eg poorly defined termination of T-wave)

- Pregnant or lactating females or females actively trying to conceive.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 millilitres 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.

- 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.

- Subject is mentally or legally incapacitated

Part B

- Previous participation in Part A of this study (200921)

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
21/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/05/2014
Sample size
Target
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

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, two part, six period- cross over, randomised, single dose, single
centre study in healthy subjects. This is the first clinical study for the UD-DPI. This study
is divided into two parts. Part A will ascertain whether the pharmacokinetic (PK) of
salbutamol delivered via the UD-DPI is comparable to the salbutamol delivered via the Diskus
or MDI. For this reason four treatment doses consisting of three dose strength and two
percentage blends will be assessed in Part A delivered via UD-DPI. Part A will also provide
preliminary PK variability estimates to allow for better sample size/precision calculations
for Part B. Part B will explore whether the UD-DPI has a pharmacokinetic exposure profile
that is comparable to either Diskus or MDI in the presence of the charcoal block.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01984086
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/NCT01984086