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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/NCT01702350




Registration number
NCT01702350
Ethics application status
Date submitted
20/09/2012
Date registered
8/10/2012
Date last updated
28/06/2017

Titles & IDs
Public title
A Four Part Study to Investigate Relative Bioavailability, Safety and Tolerability of up to 5 Oral Formulation of GSK2251052 in Order to Identify a Formulation for Further Evaluation in a Future Later Phase Study
Scientific title
A Study to Evaluate the Relative Bioavailability of Five Different Oral Formulations of GSK2251052 and the Multiple-dose, Safety, Tolerability, and Pharmacokinetics of GSK2251052 With and Without Food in Male and Female, Young and Elderly Healthy Volunteers
Secondary ID [1] 0 0
115244
Universal Trial Number (UTN)
Trial acronym
Relative Bio
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Community-acquired Infection 0 0
Condition category
Condition code

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

Experimental: Study Drug Formulation A - Enterric Coated Tablet Formulation of GSK2251052

Experimental: Study Drug Formulation B - Modified Release Table Formulation of GSK2251052

Experimental: Study Drug Formulation C - Enterric Coated Powder for Oral Suspension Formulation of GSK2251052

Experimental: Study Drug Formulation D - Immidiate Release Table Formulation of GSK2251052

Experimental: Study Drug Formulation E - Oral Solution Formulation of GSk2251052


Treatment: Drugs: GSK2251052
Oral formulation of an an antibacterial
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Single dose relative bioavailability of five formulations
Timepoint [1] 0 0
3 days
Primary outcome [2] 0 0
Pharamacokinetics of escalating single oral doses
Timepoint [2] 0 0
4 days
Primary outcome [3] 0 0
To evaluate and compare the pharmacokinetics of multiple oral doses of GSK2251052 in young and elderly healthy adult subjects
Timepoint [3] 0 0
Days 1 to 4 and day 9
Secondary outcome [1] 0 0
Safety and tolerability in Part A
Timepoint [1] 0 0
Days 1 to 4 and day 14 post-dose in periods 3
Secondary outcome [2] 0 0
Safety and tolerability in Part B
Timepoint [2] 0 0
Days 1 to4 and day 14 post dose in period 3
Secondary outcome [3] 0 0
Part C and Part D, to assess the safety and tolerability of GSK2251502 in healthy young and elderly volunteers following single and repeat dose administration with and without food
Timepoint [3] 0 0
Days 1 to 4 and day 9 and day 14 post last dose in period 2.

Eligibility
Key inclusion criteria
- AST, ALT, alkaline phosphatase and bilirubin =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 enrolment.

- Part A, Part B, and young healthy cohort in Parts C and D: Male or female between 18
and 64 years of age inclusive, at the time of signing the informed consent. Part C and
Part D for healthy elderly cohorts: Male or female =65 years of age 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 greater than 40 MlU/ml and estradiol less than 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
64 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 (appromimately 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. However, in elderly cohorts of
Part C and Part D, use of concomitant medications may be considered on a case by case
basis by the PI in consultation with the GSK Medical monitor.

- 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 protocol14.
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 recent history of symptomatic orthostatic hypotension.

Study design
Purpose of the study
Other
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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/10/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/12/2011
Sample size
Target
Accrual to date
Final
24
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 is a member of a novel mechanistic and structural class of antibiotics that
inhibits the bacterial enzyme leucyl tRNA synthetase (LeuRS) by forming a boron adduct with
tRNA and is currently in development for the treatment of hospital acquired Gramnegative
infections.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01702350
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/NCT01702350