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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/NCT01262885




Registration number
NCT01262885
Ethics application status
Date submitted
16/12/2010
Date registered
17/12/2010
Date last updated
28/06/2017

Titles & IDs
Public title
A Randomized, Single Blind, Placebo Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses and Repeat Escalating Oral Doses of GSK2251052 in Healthy Adult Subjects
Scientific title
A Randomized, Single Blind, Placebo Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses and Repeat Escalating Oral Doses of GSK2251052 in Healthy Adult Subjects
Secondary ID [1] 0 0
114470
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infections, Bacterial 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2251052
Treatment: Drugs - Placebo

Experimental: Part A Cohort 1 - GSK2251052 500 mg (6 subjects), Placebo (1 subject)

Experimental: Part A Cohort 2 - GSK2251052 1000 mg (6 subjects), Placebo (1 subject)

Experimental: Part A Cohort 3 - GSK2251052 2000 mg (6 subjects), Placebo (1 subject)

Experimental: Part A Cohort 2 - fed - GSK2251052 1000 mg (6 subjects), Placebo (1 subject)

Experimental: Part B Cohort 1 - Placebo (3 subjects), GSK2251052 (9 subjects) dose to be determined

Experimental: Part B Cohort 2 - Placebo (3 subjects), GSK2251052 (9 subjects) dose to be determined

Experimental: Part B Cohort 3 - Placebo (3 subjects), GSK2251052 (9 subjects) dose to be determined

Experimental: Part A Cohort 4 - Placebo (1 subject), GSK2251052 (6 subjects) dose to be determined


Treatment: Drugs: GSK2251052
500 mg tablet, dose levels detailed in Arm description

Treatment: Drugs: Placebo
matching placebo tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse event reporting, clinical laboratory tests, vital signs, cardiac monitoring, urinalysis, and clinical monitoring/observation.
Timepoint [1] 0 0
within 35 days of first dose
Primary outcome [2] 0 0
Plasma AUC(0-t), AUC(0-inf), Cmax, tmax, t1/2, Ae, fe, and CLr of GSK2251052 as data permit.
Timepoint [2] 0 0
within 14 days of first dose
Secondary outcome [1] 0 0
AUC(0-t), AUC(0-inf), and Cmax following single dose administration for the assessment of dose proportionality
Timepoint [1] 0 0
within 72 h of dosing
Secondary outcome [2] 0 0
Trough plasma concentrations
Timepoint [2] 0 0
within 10 days of first dose
Secondary outcome [3] 0 0
Accumulation based on AUC(Ro) and Cmax (RCmax) and determine the steady-state ratio (Rss)
Timepoint [3] 0 0
within 14 days of first dose
Secondary outcome [4] 0 0
AUC(0-t)am and Cmax,am following repeat administration at different doses for the assessment of dose proportionality
Timepoint [4] 0 0
within 14 days of first dose

Eligibility
Key inclusion criteria
- AST, ALT, alkaline phosphatase and bilirubin < or = 1.5xULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

- Abnormal LFT tests may be repeated once at the discretion of the Investigator. If an
abnormality is repeated, the subject would not be eligible for inclusion.

- 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
outside the reference range for the population being studied may be included only if
the Investigator and the GSK Medical Monitor agree that the finding is unlikely to
introduce additional risk factors and will not interfere with the study procedures.
Subjects with coagulation, reticulocyte, or Hgb values outside the normal range should
always be excluded from enrollment.

- Male or female between 18 and 65 years of age inclusive, at the time of signing the
informed consent.

- 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 (<147 pmol/L) is
confirmatory].

- Male subjects with female partners of child-bearing potential must agree to use one of
the contraception methods listed in Section 8.1. This criterion must be followed from
the time of the first dose of study medication until at least 90 days post-last dose.

- Body weight > 50 kg and BMI within the range 19 - 32 kg/m2 (inclusive).

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

- QTc, QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening

- 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 drug/alcohol screen.

- A positive test for HIV antibody.

- 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. One unit is
equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine
or 1 (25 ml) measure of spirits.

- 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.

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) prior to the first dose of study medication, unless in the
opinion of the Investigator and GSK Medical Monitor the medication will not interfere
with the study procedures or compromise subject safety.

- 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.

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

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

- Lactating females.

- Unwillingness or inability to follow the procedures outlined in the protocol.

- Subject is mentally or legally incapacitated.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Subjects who have asthma or a history of asthma, (e.g., for any FTIH where risk of
bronchoconstriction is unknown, or compound specific where risk of
bronchoconstriction).

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

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

- A history of orthostatic hypotension

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
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
7/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/08/2011
Sample size
Target
Accrual to date
Final
84
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
GSK Investigational Site - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

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

Ethics approval
Ethics application status

Summary
Brief summary
GSK2251052 ((S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole
hydrochloride) is a Gram negative antibacterial compound currently in development for the
treatment of hospital acquired Gram negative infection (including E. coli, K. pneumoniae, and
Enterobacter spp.) This study will be conducted in two (2) parts, with single oral doses
being explored in Part A (500, 1000, and 2000 mg) and repeat oral doses (1000 and 2000 mg,
b.i.d.) being explored in Part B. Parts A and B will be single-blind, randomized,
placebo-controlled, dose-rising studies in healthy subjects to evaluate the safety,
tolerability and pharmacokinetics of oral GSK2251052.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01262885
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/NCT01262885